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Aschner A, Kowal C, Arski O, Crispo JAG, Farhat N, Donner E. Prevalence of epileptiform electroencephalographic abnormalities in people without a history of seizures: A systematic review and meta-analysis. Epilepsia 2024; 65:583-599. [PMID: 38101821 DOI: 10.1111/epi.17864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 12/12/2023] [Accepted: 12/12/2023] [Indexed: 12/17/2023]
Abstract
Abnormal patterns identified on electroencephalogram (EEG) are one of the primary diagnostic tests for epilepsy. However, epidemiological studies have established that both benign and epileptiform abnormalities (EAs) occur on the EEG of nonepileptic, seizure-free people as well. The reported rates of EAs in nonepileptic, seizure-free populations vary, and the true prevalence is unknown. The primary objective of this systematic review and meta-analysis was to estimate the overall prevalence of EAs in the EEG of people without a history of seizures. Secondary aims were to characterize (1) the cortical localization of focal abnormalities, (2) the proportion of findings that occurred during standard EEG stimulation protocols, and (3) the persistence and implications of abnormalities at follow-up. A comprehensive electronic search of six bibliographic databases was completed: Embase, MEDLINE, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register for Controlled Trials, and Web of Science. No search date restrictions were applied. Overall effect size was calculated using a generalized linear mixed-effects model. Fifty-three studies, totaling 73 990 individuals, met our inclusion criteria. The overall point prevalence of EAs was 1.74% (95% confidence interval [CI] = 1.13-2.67). Due to the risk of bias in the literature, especially from participant selection, we believe this to be an overestimate of the true prevalence. Prevalence of EAs was greater in children (2.45%, 95% CI = 1.41-4.21) and the elderly (5.96%, 95% CI = 1.39-22.13) compared with adults (.93%, 95% CI = .48-1.80). Reports of developing epilepsy after an EA-positive EEG were rare. The likelihood of subsequent positive findings on follow-up EEG may be as high as 50%. Our study has limitations in that males were overrepresented in the study samples, there is substantial heterogeneity among studies, and many studies provided insufficient detail about their exclusion criteria. Nonetheless, our estimates provide benchmark data for future studies examining EAs in clinical populations, particularly behavioral and psychiatric populations.
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Affiliation(s)
- Amir Aschner
- Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Christine Kowal
- Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Olivia Arski
- Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - James A G Crispo
- Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
- Human Sciences Division, Northern Ontario School of Medicine University, Sudbury, Ontario, Canada
- TruEffect, Sudbury, Ontario, Canada
| | - Nawal Farhat
- TruEffect, Sudbury, Ontario, Canada
- School of Mathematics and Statistics, Carleton University, Ottawa, Ontario, Canada
| | - Elizabeth Donner
- Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
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Gümüş E, Özen H. Glycogen storage diseases: An update. World J Gastroenterol 2023; 29:3932-3963. [PMID: 37476587 PMCID: PMC10354582 DOI: 10.3748/wjg.v29.i25.3932] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/15/2023] [Accepted: 04/30/2023] [Indexed: 06/28/2023] Open
Abstract
Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.
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Affiliation(s)
- Ersin Gümüş
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children’s Hospital, Ankara 06230, Turkey
| | - Hasan Özen
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children’s Hospital, Ankara 06230, Turkey
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Iwanicka-Pronicka K, Trubicka J, Szymanska E, Ciara E, Rokicki D, Pollak A, Pronicki M. Sensorineural hearing loss in GSD type I patients. A newly recognized symptomatic association of potential clinical significance and unclear pathomechanism. Int J Pediatr Otorhinolaryngol 2021; 151:110970. [PMID: 34775139 DOI: 10.1016/j.ijporl.2021.110970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 10/15/2021] [Accepted: 11/08/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE Glycogen storage disease (GSD) type I is an inborn error of carbohydrates metabolism characterized by inability to convert glucose-6-phosphate to glucose. It presents with serious liver and metabolic complications, as well as in type Ib with severe infections due to neutropenia. So far, the sensorineural hearing impairment has not been reported in these patients. Bilateral, sensorineural hearing impairment was diagnosed in four unrelated GSDI patients. Congenital origin of hearing loss and descending audiometric curves warranted the need for future investigations. METHODS Hearing status was assessed in entire group of 40 children with GSD type I. Then, molecular testing, massive parallel sequencing was performed in the four probands and their parents in order to find possible genetic background of auditory dysfunction in these patients. RESULTS Pathogenic variants in G6PC and SLC37A4 related to the phenotypes of GSDI subtype Ia and subtype Ib were detected, each in two probands, respectively. No change in the genes involved in auditory pathway dysfunction was found. CONCLUSIONS Sensorineural hearing loss appears to be associated with GSDI in approximately one out of ten cases. Careful assessment and monitoring of auditory functions of patients with GSDI is recommended.
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Affiliation(s)
- Katarzyna Iwanicka-Pronicka
- Department of Audiology and Phoniatrics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland; Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland.
| | - Joanna Trubicka
- Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland; Department of Pathology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland
| | - Edyta Szymanska
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Childrens' Memorial Health Institute, Warsaw, Poland, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland; Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland
| | - Elżbieta Ciara
- Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland
| | - Dariusz Rokicki
- Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland
| | - Agnieszka Pollak
- Department of Medical Genetics, Medical University of Warsaw, A. Pawinskiego 3c, 02-106, Warszaw, Poland
| | - Maciej Pronicki
- Department of Pathology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20; 04-730, Warsaw, Poland
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Muzetti JH, do Valle DA, Santos MLSF, Telles BA, Cordeiro ML. Neurological Characteristics of Pediatric Glycogen Storage Disease. Front Endocrinol (Lausanne) 2021; 12:685272. [PMID: 34093448 PMCID: PMC8176209 DOI: 10.3389/fendo.2021.685272] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 04/28/2021] [Indexed: 11/13/2022] Open
Abstract
Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.
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Affiliation(s)
- Julio Henrique Muzetti
- Faculdades Pequeno Príncipe, Curitiba, Brazil
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil
- Department of Child Neurology, Hospital Pequeno Príncipe, Curitiba, Brazil
| | - Daniel Almeida do Valle
- Faculdades Pequeno Príncipe, Curitiba, Brazil
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil
- Department of Child Neurology, Hospital Pequeno Príncipe, Curitiba, Brazil
| | | | | | - Mara L. Cordeiro
- Faculdades Pequeno Príncipe, Curitiba, Brazil
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil
- Department of Psychiatry and Biological Behavioral Sciences, University of California Los Angeles, Los Angeles, CA, United States
- *Correspondence: Mara L. Cordeiro, ; orcid.org/0000-0002-0235-8001
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Bindi V, Eiroa HD, Crespo C, Martinez M, Bay L. Clinical, Biochemical and Molecular Characterization of a Cohort of Glycogen Storage Disease Type I Patients in a High Complexity Hospital in Argentina. JOURNAL OF INBORN ERRORS OF METABOLISM AND SCREENING 2021. [DOI: 10.1590/2326-4594-jiems-2020-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
| | | | | | | | - Luisa Bay
- Hospital de Pediatría Juan P. Garrahan, Argentina
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Rosa-Silva HTD, Panzenhagen AC, Schmidtt V, Alves Teixeira A, Espitia-Pérez P, de Oliveira Franco Á, Mingori M, Torres-Ávila JF, Schnorr CE, Hermann PRS, Moraes DP, Almeida RF, Moreira JCF. Hepatic and neurobiological effects of foetal and breastfeeding and adulthood exposure to methylmercury in Wistar rats. CHEMOSPHERE 2020; 244:125400. [PMID: 31809933 DOI: 10.1016/j.chemosphere.2019.125400] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 10/20/2019] [Accepted: 11/17/2019] [Indexed: 06/10/2023]
Abstract
Methylmercury (MeHg) is an organic bioaccumulated mercury derivative that strongly affects the environment and represents a public health problem primarily to riparian communities in South America. Our objective was to investigate the hepatic and neurological effects of MeHg exposure during the phases foetal and breast-feeding and adult in Wistar rats. Wistar rats (n = 10) were divided into 3 groups. Control group received mineral oil; The simple exposure (SE) group was exposed only in adulthood (0.5 mg/kg/day); and double exposure (DE) was pre-exposed to MeHg 0.5 mg/kg/day during pregnancy and breastfeeding (±40 days) and re-exposed to MeHg for 45 days from day 100. After, we evaluated possible abnormalities. Behavioral and biochemical parameters in liver and occipital cortex (CO), markers of liver injury, redox and AKT/GSK3β/mTOR signaling pathway. Our results showed that both groups treated with MeHg presented significant alterations, such as decreased locomotion and exploration and impaired visuospatial perception. The rats exposed to MeHg showed severe liver damage and increased hepatic glycogen concentration. The MeHg groups showed significant impairment in redox balance and oxidative damage to liver macromolecules and CO. MeHg upregulated the AKT/GSK3β/mTOR pathway and the phosphorylated form of the Tau protein. In addition, we found a reduction in NeuN and GFAP immunocontent. These results represent the first approach to the hepatotoxic and neural effects of foetal and adult MeHg exposure.
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Affiliation(s)
- Helen Tais da Rosa-Silva
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
| | - Alana Castro Panzenhagen
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Victória Schmidtt
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Alexsander Alves Teixeira
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Pedro Espitia-Pérez
- Facultad de Ciencias de la Salud, Laboratorio de Investigación Biomédica y Biología Molecular, Universidad del Sinú, Córdoba, Colombia
| | - Álvaro de Oliveira Franco
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Moara Mingori
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - José F Torres-Ávila
- Unit for Development and Innovation in Genetics and Molecular Biology, Universidad Simón Bolívar, Barranquilla, Atlántico, Colombia
| | - Carlos Eduardo Schnorr
- Departamento de Civil y Ambiental, Programa de Ingeniería Ambiental, Universidad de la Costa, Barranquilla, Atlántico, Colombia
| | - Paolla Rissi Silva Hermann
- Instituto de Química, Sala 103, Campus do Vale, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Diogo Pompéu Moraes
- Instituto de Química, Sala 103, Campus do Vale, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Roberto Farina Almeida
- Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
| | - José Cláudio Fonseca Moreira
- Centro de Estudos em Estresse Oxidativo, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
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Tommaso AMAD, Hessel G, Riccetto AG, Semenzati GDO, Gusmão RJ. PRE AND POST-OPERATIVE OTORHINOLARYNGOLOGY SURGERY CARE IN PATIENTS WITH GLYCOGEN STORAGE DISEASE TYPE 1. REVISTA PAULISTA DE PEDIATRIA 2019; 37:516-519. [PMID: 31291441 PMCID: PMC6821486 DOI: 10.1590/1984-0462/;2019;37;4;00005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Accepted: 04/29/2018] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To discuss aspects of pre and post-operative otorhinolaryngology surgery in patients with glycogen storage disease type 1b. CASE DESCRIPTION Description of three clinical cases with probable glycogen storage disease type 1b who underwent otorhinolaryngology surgery, showing the importance of multidisciplinary interaction to avoid episodes of hypoglycemia. COMMENTS Patients with glycogen storage disease type 1b present recurrent infections, including the otorhinolaryngology affections. When there is an indication for surgical treatment, the caloric intake should be carefully followed in order to prevent hypoglycemia. The way to ensure this is to perform the pre and postoperative period in the hospital ward. In the postoperative period, it is important to make a slow transition between the intravenous and oral routes and not suspend the infusion of glucose during the surgical procedure. The cases illustrate the need for the interaction of the otorhinolaryngologic surgeon with the anesthesiologist, the pediatrician and the gastro-pediatrician in the management of these patients, avoiding hypoglycemic episodes.
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Affiliation(s)
| | - Gabriel Hessel
- Universidade Estadual de Campinas, São Paulo, SP, Brazil
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Kishnani PS, Goldstein J, Austin SL, Arn P, Bachrach B, Bali DS, Chung WK, El-Gharbawy A, Brown LM, Kahler S, Pendyal S, Ross KM, Tsilianidis L, Weinstein DA, Watson MS. Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2019; 21:772-789. [PMID: 30659246 DOI: 10.1038/s41436-018-0364-2] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 10/15/2018] [Indexed: 01/10/2023] Open
Abstract
PURPOSE Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD VI is caused by deficient activity of hepatic glycogen phosphorylase, an enzyme encoded by the PYGL gene. GSD IX is caused by deficient activity of phosphorylase kinase (PhK), the enzyme subunits of which are encoded by various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (PHKG1, PHKG2), and δ (CALM1, CALM2, CALM3). Glycogen storage disease types VI and IX have a wide spectrum of clinical manifestations and often cannot be distinguished from each other, or from other liver GSDs, on clinical presentation alone. Individuals with GSDs VI and IX can present with hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth. This guideline for the management of GSDs VI and IX was developed as an educational resource for health-care providers to facilitate prompt and accurate diagnosis and appropriate management of patients. METHODS A national group of experts in various aspects of GSDs VI and IX met to review the limited evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management. Evidence bases for these rare disorders are largely based on expert opinion, particularly when targeted therapeutics that have to clear the US Food and Drug Administration (FDA) remain unavailable. RESULTS This management guideline specifically addresses evaluation and diagnosis across multiple organ systems involved in GSDs VI and IX. Conditions to consider in a differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, and prenatal diagnosis are addressed. CONCLUSION A guideline that will facilitate the accurate diagnosis and optimal management of patients with GSDs VI and IX was developed. This guideline will help health-care providers recognize patients with GSDs VI and IX, expedite diagnosis, and minimize adverse sequelae from delayed diagnosis and inappropriate management. It will also help identify gaps in scientific knowledge that exist today and suggest future studies.
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Affiliation(s)
| | | | | | - Pamela Arn
- Nemours Children's Clinic, Jacksonville, FL, USA
| | - Bert Bachrach
- University of Missouri Health System, Columbia, MO, USA
| | | | - Wendy K Chung
- Columbia University Medical Center, New York, NY, USA
| | | | - Laurie M Brown
- University of Florida College of Medicine, Gainesville, FL, USA
| | | | | | - Katalin M Ross
- Connecticut Children's Medical Center, Hartford, CT, USA
| | | | - David A Weinstein
- University of Connecticut School of Medicine, Connecticut Children's Hospital, Hartford, CT, USA
| | - Michael S Watson
- American College of Medical Genetics and Genomics, Bethesda, MD, USA.
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GLUT-1 deficiency presenting with seizures and reversible leukoencephalopathy on MRI imaging. Eur J Paediatr Neurol 2018; 22:1161-1164. [PMID: 30115503 DOI: 10.1016/j.ejpn.2018.02.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 01/07/2018] [Accepted: 02/05/2018] [Indexed: 12/21/2022]
Abstract
Glucose transporter type 1 (GLUT1) deficiency syndrome is a well recognised genetic neurometabolic disorder typically presenting with progressive encephalopathy, acquired microcephaly and drug-resistant epilepsy. Imaging is normal in the majority. Here we describe a 5-month-old boy who presented with motor delay, myoclonic jerks and tonic-clonic seizures. His MRI brain scan revealed confluent symmetrical T2 hyperintense signal abnormality in both anterior frontal lobes and delayed myelination. Neurometabolic screen revealed low CSF glucose and lactate levels. A pathogenic de novo heterozygous mutation in SLC2A1 (c.275+1G > A) confirmed the diagnosis of GLUT1 deficiency. Ketogenic diet resulted in a dramatic termination of his seizures at 72 h. At 15 months, he continued to be seizure free with marked developmental catch up. Repeat imaging revealed a significant resolution of the previously seen changes. This case suggests that GLUT1 deficiency should be considered in the differential diagnosis of infants with suspected genetic leukoencephalopathies with important treatment implications.
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Rousseau-Nepton I, Huot C, Laforte D, Mok E, Fenyves D, Constantin E, Mitchell J. Sleep and quality of life of patients with glycogen storage disease on standard and modified uncooked cornstarch. Mol Genet Metab 2018; 123:326-330. [PMID: 29223626 DOI: 10.1016/j.ymgme.2017.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Revised: 09/08/2017] [Accepted: 09/09/2017] [Indexed: 11/23/2022]
Abstract
BACKGROUND Glycemic control in hepatic glycogen storage diseases (GSDs) relies on specific nutritional recommendations, including strict avoidance of a fasting period. Uncooked cornstarch (UCCS) is an important therapeutic component. A new modified UCCS, Glycosade™, was created with the objective of prolonging euglycemia. We aimed to determine the length of euglycemia on Glycosade™ using a continuous glucose monitor (CGM) and to evaluate whether longer euglycemia and thus less nighttime interruptions would improve sleep and quality of life (QoL) after the introduction of the modified cornstarch. METHODS We conducted a prospective cohort study to assess quality and quantity of sleep and quality of life (QoL) in patients with GSDs on standard UCCS and after the introduction of Glycosade™. Sleep and QoL evaluation was done for patients using validated questionnaires, a standardized sleep diary and actigraphy. Length of fast and glucose variability were determined with CGM. RESULTS Nine adults with GSD Ia took part in the study. Glycosade™ introduction was done under close supervision during a hospital admission. Comparison of sleep in 9 patients showed sleep disturbances on standard UCCS that were improved with Glycosade™. QoL was normal both pre and post Glycosade™. The CGM confirmed maintenance of a longer fasting period with Glycosade™ at home. CONCLUSION Glycosade™ represents an alternative option for GSD patients. We showed possible benefits in terms of sleep quality. We also confirmed the longer length of fast on Glycosade™. SYNOPSIS A new modified form of uncooked starch for patients with glycogen storage disease represents an alternative option as it showed a longer length of fast and improvements in sleep quality.
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Affiliation(s)
- Isabelle Rousseau-Nepton
- Department of Pediatrics, Division of Pediatric Endocrinology, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada
| | - Céline Huot
- Department of Pediatrics, Division of Pediatric Endocrinology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
| | - Diane Laforte
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada
| | - Elise Mok
- Research Institute - McGill University Health Centre, Montreal, Quebec, Canada
| | - Daphna Fenyves
- Department of Medicine, Division of Hepatology, Hôpital St-Luc du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada
| | - Evelyn Constantin
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
| | - John Mitchell
- Department of Pediatrics, Division of Pediatric Endocrinology, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
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De Leon DD, Stanley CA. Congenital Hypoglycemia Disorders: New Aspects of Etiology, Diagnosis, Treatment and Outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016. Pediatr Diabetes 2017; 18:3-9. [PMID: 27753189 PMCID: PMC5473026 DOI: 10.1111/pedi.12453] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 09/08/2016] [Indexed: 12/19/2022] Open
Abstract
Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism (HI) is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of HI have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular, and imaging findings to establish the appropriate treatment according to the subtype. Here we present a summary of a recent international symposium on congenital hypoglycemia disorders with emphasis on novel molecular mechanisms resulting in HI, genetic diagnosis, overall approach to management, novel therapies under development, and current outcomes.
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Affiliation(s)
- Diva D. De Leon
- The Children's Hospital of Philadelphia Congenital Hyperinsulinism Center and the Department of Pediatrics; Perelman School of Medicine at the University of Pennsylvania; Philadelphia Pennsylvania
| | - Charles A. Stanley
- The Children's Hospital of Philadelphia Congenital Hyperinsulinism Center and the Department of Pediatrics; Perelman School of Medicine at the University of Pennsylvania; Philadelphia Pennsylvania
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In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders. Neurochem Res 2015; 40:2647-85. [PMID: 26610379 DOI: 10.1007/s11064-015-1772-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Revised: 11/10/2015] [Accepted: 11/12/2015] [Indexed: 01/09/2023]
Abstract
Metabolic disorders, whether hereditary or acquired, affect the brain, and abnormalities of the brain are related to cellular integrity; particularly in regard to neurons and astrocytes as well as interactions between them. Metabolic disturbances lead to alterations in cellular function as well as microscopic and macroscopic structural changes in the brain with diabetes, the most typical example of metabolic disorders, and a number of hereditary metabolic disorders. Alternatively, cellular dysfunction and degeneration of the brain lead to metabolic disturbances in hereditary neurological disorders with neurodegeneration. Nuclear magnetic resonance (NMR) techniques allow us to assess a range of pathophysiological changes of the brain in vivo. For example, magnetic resonance spectroscopy detects alterations in brain metabolism and energetics. Physiological magnetic resonance imaging (MRI) detects accompanying changes in cerebral blood flow related to neurovascular coupling. Diffusion and T1/T2-weighted MRI detect microscopic and macroscopic changes of the brain structure. This review summarizes current NMR findings of functional, physiological and biochemical alterations within a number of hereditary and acquired metabolic disorders in both animal models and humans. The global view of the impact of these metabolic disorders on the brain may be useful in identifying the unique and/or general patterns of abnormalities in the living brain related to the pathophysiology of the diseases, and identifying future fields of inquiry.
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Kroczka S, Biedroń A, Kaciński M. Epilepsy and electrophysiological findings in polish twins with glycogenosis type IIIb. Clin EEG Neurosci 2014; 45:201-4. [PMID: 24357677 DOI: 10.1177/1550059413500276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Glycogen storage diseases are rare genetic disorders, mostly autosomal recessively inherited. Abnormal accumulation is because of the lack of one of the enzymes involved in glycogen metabolism. Neurological manifestation of the diseases involves muscle weakness and hypoglycemia-induced seizures. In this article, we present a history of twin sisters with unusual coincidence of glycogenosis type IIIb and epilepsy. Hypoglycemic background of seizures and organic changes of the central nervous system were excluded. Since the introduction of antiepileptic treatment, the patients have been seizure-free; however, paroxysmal electroencephalographic (EEG) changes have persisted. A high-protein and low-carbohydrate diet has protected them against hypoglycemia.
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El-Karaksy H, Anwar G, El-Raziky M, Mogahed E, Fateen E, Gouda A, El-Mougy F, El-Hennawy A. Glycogen storage disease type III in Egyptian children: a single centre clinico-laboratory study. Arab J Gastroenterol 2014; 15:63-67. [PMID: 25097048 DOI: 10.1016/j.ajg.2014.01.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 01/09/2014] [Accepted: 01/20/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND AND STUDY AIMS Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability. PATIENTS AND METHODS We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt. RESULTS Eighteen patients (58%) were males. Their ages ranged between 6 months to 12 years. The main presenting complaint was progressive abdominal distention in 55%. Twelve patients (38.7%) had a history of recurrent attacks of convulsions; four had an erroneous diagnosis of hypocalcaemia and epilepsy. Doll-like facies was noted in 90%. Abdominal examination of all cases revealed abdominal distention and soft hepatomegaly which had bright echogenicity by ultrasound. Hypertriglyceridaemia was present in 93.6%, hyperlactacidaemia in 51.6% and hyperuricaemia in 19.4%. Liver biopsy showed markedly distended hepatocytes with well distinct cytoplasmic boundaries and 32% had macrovesicular fatty changes. Serum creatine kinase was elevated in 64.6% of patients and correlated positively and significantly with age (r=0.7 and P=<0.001), while serum triglycerides correlated negatively with age (r=-0.4 and P=0.05). CONCLUSION Blood glucose assessment and search for hepatomegaly in an infant with recurrent seizures may prevent delay in the diagnosis. A huge soft liver reaching the left midclavicular line that appears echogenic on ultrasonography is characteristic of GSD III. A distended hepatocyte with rarified cytoplasm is pathognomonic but not diagnostic. Hypertriglyceridaemia correlates negatively with age, in contrary to CK level.
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Affiliation(s)
- Hanaa El-Karaksy
- Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Ghada Anwar
- Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mona El-Raziky
- Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Engy Mogahed
- Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ekram Fateen
- Biochemical Genetic Department, National Research Center, Cairo, Egypt
| | - Amr Gouda
- Biochemical Genetic Department, National Research Center, Cairo, Egypt
| | - Fatma El-Mougy
- Department of Chemical Pathlogy, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed El-Hennawy
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
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15
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Lerner DP, Dombrowski K. Focal neuronal dysfunction resulting in subclinical status epilepticus in von Gierke's disease. Int J Neurosci 2014; 125:228-31. [PMID: 24825586 DOI: 10.3109/00207454.2014.923420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- David P Lerner
- Department of Neurology, Duke University Medical Center, DUMC 2905, Durham, NC, USA
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Shiohama T, Fujii K, Takahashi S, Nakamura F, Kohno Y. Reversible white matter lesions during ketogenic diet therapy in glucose transporter 1 deficiency syndrome. Pediatr Neurol 2013; 49:493-6. [PMID: 24080273 DOI: 10.1016/j.pediatrneurol.2013.06.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Revised: 06/05/2013] [Accepted: 06/09/2013] [Indexed: 11/30/2022]
Abstract
BACKGROUND Glucose transporter type 1 deficiency syndrome is caused by brain energy failure resulting from a disturbance in glucose transport. PATIENTS We describe a 4-year-old boy with classical type glucose transporter type 1 deficiency syndrome with a heterozygous splice acceptor site mutation (c.517-2A>G) in the SLCA2A1 gene. RESULTS We initiated a ketogenic diet at 4 months of age. However, even though his condition was good during ketogenic diet therapy, multiple cerebral white matter and right cerebellum lesions appeared at 9 months of age. The lesions in the cerebral white matter subsequently disappeared, indicating that white matter lesions during diet therapy may be reversible and independent of the ketogenic diet. CONCLUSIONS This is the first report of reversible white matter lesions during ketogenic diet therapy in glucose transporter type 1 deficiency syndrome.
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Affiliation(s)
- Tadashi Shiohama
- Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
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Glycogen Storage Disease type 1a - a secondary cause for hyperlipidemia: report of five cases. J Diabetes Metab Disord 2013; 12:25. [PMID: 23738826 PMCID: PMC3937210 DOI: 10.1186/2251-6581-12-25] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2012] [Accepted: 05/27/2013] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIMS Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Hyperlipidemia and hyperuricemia are almost always present and hepatocellular adenomas and renal dysfunction frequent late complications. METHODS The authors present a report of five adult patients with GSD Ia followed in internal medicine appointments and subspecialties. RESULTS Four out of five patients were diagnosed in the first 6 months of life, while the other one was diagnosed in adult life after the discovery of hepatocellular adenomas. In two cases genetic tests were performed, being identified the missense mutation R83C in one, and the mutation IVS4-3C > G in the intron 4 of glucose-6-phosphatase gene, not previously described, in the other. Growth retardation was present in 3 patients, and all of them had anemia, increased bleeding tendency and hepatocellular adenomas; osteopenia/osteoporosis was present in three cases. All but one patient had marked hyperlipidemia and hyperuricemia, with evidence of endothelial dysfunction in one case and of brain damage with refractory epilepsy in another case. Proteinuria was present in two cases and end-stage renal disease in another case. There was a great variability in the dietary measures; in one case, liver transplantation was performed, with correction of the metabolic derangements. CONCLUSIONS Hyperlipidemia is almost always present and only partially responds to dietary and drug therapy; liver transplantation is the only definitive solution. Although its association with premature atherosclerosis is rare, there have been reports of endothelial dysfunction, raising the possibility for increased cardiovascular risk in this group of patients. Being a rare disease, no single metabolic center has experience with large numbers of patients and the recommendations are based on clinical experience more than large scale studies.
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Della Casa R, Ungaro C, Acampora E, Pignata C, Vajro P, Salerno M, Santamaria F, Parenti G. A case of galactosemia misdiagnosed as cow's milk intolerance. Ital J Pediatr 2012; 38:47. [PMID: 22992216 PMCID: PMC3462687 DOI: 10.1186/1824-7288-38-47] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 09/11/2012] [Indexed: 12/12/2022] Open
Abstract
We report on a female patient affected by galactosemia in whom the diagnosis was obscured by the concomitant presence of manifestations suggesting a cow's milk intolerance. This case exemplifies the problems in reaching a correct diagnosis in patients with metabolic diseases.
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Wyrwoll CS, Holmes MC, Seckl JR. 11β-hydroxysteroid dehydrogenases and the brain: from zero to hero, a decade of progress. Front Neuroendocrinol 2011; 32:265-86. [PMID: 21144857 PMCID: PMC3149101 DOI: 10.1016/j.yfrne.2010.12.001] [Citation(s) in RCA: 178] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2010] [Revised: 12/01/2010] [Accepted: 12/01/2010] [Indexed: 12/11/2022]
Abstract
Glucocorticoids have profound effects on brain development and adult CNS function. Excess or insufficient glucocorticoids cause myriad abnormalities from development to ageing. The actions of glucocorticoids within cells are determined not only by blood steroid levels and target cell receptor density, but also by intracellular metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSD). 11β-HSD1 regenerates active glucocorticoids from their inactive 11-keto derivatives and is widely expressed throughout the adult CNS. Elevated hippocampal and neocortical 11β-HSD1 is observed with ageing and causes cognitive decline; its deficiency prevents the emergence of cognitive defects with age. Conversely, 11β-HSD2 is a dehydrogenase, inactivating glucocorticoids. The major central effects of 11β-HSD2 occur in development, as expression of 11β-HSD2 is high in fetal brain and placenta. Deficient feto-placental 11β-HSD2 results in a life-long phenotype of anxiety and cardiometabolic disorders, consistent with early life glucocorticoid programming.
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Affiliation(s)
- Caitlin S Wyrwoll
- Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
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Boudjemline AM, Isapof A, Witas JB, Petit FM, Gajdos V, Labrune P. Klüver Bucy syndrome following hypoglycaemic coma in a patient with glycogen storage disease type Ib. J Inherit Metab Dis 2010; 33 Suppl 3:S477-80. [PMID: 21103936 DOI: 10.1007/s10545-010-9243-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2010] [Revised: 09/27/2010] [Accepted: 10/20/2010] [Indexed: 10/18/2022]
Abstract
Patients with type I glycogen storage disease (GSD) have poor tolerance to fasting, sometimes less than 3 hours during infancy. Even though most patients are able, as they get older, to tolerate a longer fasting period, they are at permanent risk for fast-induced hypoglycaemia, even in adulthood. Klüver Bucy syndrome, is characterized by psychic blindness (inability to recognize familiar objects), hypermetamorphosis (strong tendency to react to visual stimulus), increased oral exploration, placidity, indiscriminate hyper-sexuality and change in dietary habits. In this case report, we describe the development of Klüver Bucy syndrome in a 28-year-old man with type Ib GSD, following prolonged and severe hypoglycaemia triggered by a common respiratory infection.
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Abstract
Glycogen storage diseases (GSDs) are a group of inherited disorders characterized by enzyme defects that affect the glycogen synthesis and degradation cycle, classified according to the enzyme deficiency and the affected tissue. The understanding of GSD has increased in recent decades, and nutritional management of some GSDs has allowed better control of hypoglycemia and metabolic complications. However, growth failure and liver, renal, and other complications are frequent problems in the long-term outcome. Hypoglycemia is the main biochemical consequence of GSD type I and some of the other GSDs. The basis of dietary therapy is nutritional manipulation to prevent hypoglycemia and improve metabolic dysfunction, with the use of continuous nocturnal intragastric feeding or cornstarch therapy at night and foods rich in starches with low concentrations of galactose and fructose during the day and to prevent hypoglycemia during the night.
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Labrune P, Eberschweiler PT, Boudjemline AM, Hubert-Buron A, Petit F, Gajdos V. Histoire naturelle des glycogénoses avec atteinte hépatique. Presse Med 2008; 37:1172-7. [DOI: 10.1016/j.lpm.2007.09.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2007] [Revised: 09/05/2007] [Accepted: 09/26/2007] [Indexed: 12/01/2022] Open
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Dagdelen S, Atmaca A, Alikasifoglu A, Erbas T. Pituitary hypoplasia and growth hormone deficiency in a woman with glycogen storage disease type Ia: a case report. J Med Case Rep 2008; 2:210. [PMID: 18564411 PMCID: PMC2435546 DOI: 10.1186/1752-1947-2-210] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2008] [Accepted: 06/18/2008] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION Growth retardation is one of the cardinal manifestations of glycogen storage disease type Ia. It is unclear which component of the growth hormone and/or insulin-like growth factor axis is primarily disrupted, and management of growth impairment in these patients remains controversial. Here we report the first case in the literature where glycogen storage disease type Ia is associated with pituitary hypoplasia and growth hormone deficiency. CASE PRESENTATION A 20-year-old woman with glycogen storage disease type Ia was admitted to our endocrinology department because of growth retardation. Basal and overnight growth hormone sampling at 2-hour intervals demonstrated low levels; however, provocative testing revealed a relatively normal growth hormone response. A hypoplastic anterior pituitary with preserved growth hormone response to provocative testing suggested the possibility of growth hormone neurosecretory dysfunction and/or primary pituitary involvement. CONCLUSION Pituitary hypoplasia may result from growth hormone-releasing hormone deficiency, a condition generally known as growth hormone neurosecretory dysfunction. It is an abnormality with a spontaneous and pulsatile secretion pattern, characterized by short stature, growth retardation and normal serum growth hormone response to provocative testing. However, in the case described in this report, a normal although relatively low growth hormone response during insulin tolerance testing and pituitary hypoplasia suggested that primary pituitary involvement or growth hormone neurosecretory dysfunction may occur in glycogen storage disease type Ia. This is a potential cause of growth failure associated with a lower somatotroph mass, and may explain the variable responsiveness to growth hormone replacement therapy in people with glycogen storage disease.
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Affiliation(s)
- Selcuk Dagdelen
- Hacettepe University School of Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey.
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Weghuber D, Mandl M, Krssák M, Roden M, Nowotny P, Brehm A, Krebs M, Widhalm K, Bischof MG. Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type 1: a magnetic resonance spectroscopy study. Am J Physiol Endocrinol Metab 2007; 293:E1378-84. [PMID: 17785500 DOI: 10.1152/ajpendo.00658.2006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In glycogen storage disease type 1 (GSD1), children present with severe hypoglycemia, whereas the propensity for hypoglycemia may decrease with age in these patients. It was the aim of this study to elucidate the mechanisms for milder hypoglycemia symptoms in young adult GSD1 patients. Four patients with GSD1 [body mass index (BMI) 23.2 +/- 6.3 kg/m, age 21.3 +/- 2.9 yr] and four healthy controls matched for BMI (23.1 +/- 3.0 kg/m) and age (24.0 +/- 3.1 yr) were studied. Combined (1)H/(31)P nuclear magnetic resonance spectroscopy (NMRS) was used to assess brain metabolism. Before and after administration of 1 mg glucagon, endogenous glucose production (EGP) was measured with d-[6,6-(2)H(2)]glucose and hepatic glucose metabolism was examined by (1)H/(13)C/(31)P NMRS. At baseline, GSD1 patients exhibited significantly lower rates of EGP (0.53 +/- 0.04 vs. 1.74 +/- 0.03 mg.kg(-1).min(-1); P < 0.01) but an increased intrahepatic glycogen (502 +/- 89 vs. 236 +/- 11 mmol/l; P = 0.05) and lipid content (16.3 +/- 1.1 vs. 1.4 +/- 0.4%; P < 0.001). After glucagon challenge, EGP did not change in GSD1 patients (0.53 +/- 0.04 vs. 0.59 +/- 0.24 mg.kg(-1).min(-1); P = not significant) but increased in healthy controls (1.74 +/- 0.03 vs. 3.95 +/- 1.34; P < 0.0001). In GSD1 patients, we found an exaggerated increase of intrahepatic phosphomonoesters (0.23 +/- 0.08 vs. 0.86 +/- 0.19 arbitrary units; P < 0.001), whereas inorganic phosphate decreased (0.36 +/- 0.08 vs. -0.43 +/- 0.17 arbitrary units; P < 0.01). Intracerebral ratios of glucose and lactate to creatine were higher in GSD1 patients (P < 0.05 vs. control). Therefore, hepatic defects of glucose metabolism persist in young adult GSD1 patients. Upregulation of the glucose and lactate transport at the blood-brain barrier could be responsible for the amelioration of hypoglycemic symptoms.
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Affiliation(s)
- D Weghuber
- Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria
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Autti T, Joensuu R, Aberg L. Decreased T2 signal in the thalami may be a sign of lysosomal storage disease. Neuroradiology 2007; 49:571-578. [PMID: 17334752 DOI: 10.1007/s00234-007-0220-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2006] [Accepted: 01/23/2007] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been reported. AIMS Because the finding of bilateral abnormal signal intensity of the thalamus on T2-weighted images has not been systematically reviewed, and its value as a diagnostic tool critically evaluated, we carried out a systematic review of the literature. METHODS Articles in English with 30 trios of keywords were collected from PubMed. Exclusion criteria were lack of conventional T2-weighted images in the protocol and not being a human study. Finally, 111 articles were included. The thalamus was considered affected only if mentioned in the text or in the figure legends. RESULTS Some 117 patients with various lysosomal diseases and five patients with ceruloplasmin deficiency were reported to have a bilateral decrease in T2 signal intensity. At least one article reported a bilateral decrease in signal intensity of the thalami on T2-weighted images in association with GM1 and GM2 gangliosidosis and with Krabbe's disease, aspartylglucosaminuria, mannosidosis, fucosidosis, and mucolipidosis IV. Furthermore, thalamic alteration was a consistent finding in several types of neuronal ceroid lipofuscinosis (NCL) including CLN1 (infantile NCL), CLN2 (classic late infantile NCL), CLN3 (juvenile NCL), CLN5 (Finnish variant late infantile NCL), and CLN7 (Turkish variant late infantile NCL). CONCLUSION A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease.
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Affiliation(s)
- Taina Autti
- Helsinki Medical Imaging Center, Helsinki University Central Hospital, P.O. Box 340, 00029-HUS, Helsinki, Finland.
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Ozen H. Glycogen storage diseases: new perspectives. World J Gastroenterol 2007; 13:2541-2553. [PMID: 17552001 PMCID: PMC4146814 DOI: 10.3748/wjg.v13.i18.2541] [Citation(s) in RCA: 173] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2007] [Revised: 03/30/2007] [Accepted: 03/31/2007] [Indexed: 02/06/2023] Open
Abstract
Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle.
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Affiliation(s)
- Hasan Ozen
- Division of Gastroenterology, Hepatology and Nutrition, Hacettepe University Children's Hospital, Ankara, Turkey.
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Millichap JG. Brain Damage in Glycogen Storage Disease Type I. Pediatr Neurol Briefs 2004. [DOI: 10.15844/pedneurbriefs-18-6-10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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