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Sen Sarma M, Tripathi PR. Natural history and management of liver dysfunction in lysosomal storage disorders. World J Hepatol 2022; 14:1844-1861. [PMID: 36340750 PMCID: PMC9627439 DOI: 10.4254/wjh.v14.i10.1844] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 04/21/2022] [Accepted: 09/21/2022] [Indexed: 02/06/2023] Open
Abstract
Lysosomal storage disorders (LSD) are a rare group of genetic disorders. The major LSDs that cause liver dysfunction are disorders of sphingolipid lipid storage [Gaucher disease (GD) and Niemann-Pick disease] and lysosomal acid lipase deficiency [cholesteryl ester storage disease and Wolman disease (WD)]. These diseases can cause significant liver problems ranging from asymptomatic hepatomegaly to cirrhosis and portal hypertension. Abnormal storage cells initiate hepatic fibrosis in sphingolipid disorders. Dyslipidemia causes micronodular cirrhosis in lipid storage disorders. These disorders must be keenly differentiated from other chronic liver diseases and non-alcoholic steatohepatitis that affect children and young adults. GD, Niemann-Pick type C, and WD also cause neonatal cholestasis and infantile liver failure. Genotype and liver phenotype correlation is variable in these conditions. Patients with LSD may survive up to 4-5 decades except for those with neonatal onset disease. The diagnosis of all LSD is based on enzymatic activity, tissue histology, and genetic testing. Enzyme replacement is possible in GD and Niemann-Pick types A and B though there are major limitations in the outcome. Those that progress invariably require liver transplantation with variable outcomes. The prognosis of Niemann-Pick type C and WD is universally poor. Enzyme replacement therapy has a promising role in cholesteryl ester storage disease. This review attempts to outline the natural history of these disorders from a hepatologist’s perspective to increase awareness and facilitate better management of these rare disorders.
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Affiliation(s)
- Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Parijat Ram Tripathi
- Department of Pediatric Gastroenterology, Ankura Hospital for Women and Children, Hyderabad 500072, India
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Shrestha O, Khadwal AR, Singhal M, Trehan A, Bansal D, Jain R, Pal A, Hira JK, Chhabra S, Malhotra P, Das R, Sharma P. A high frequency of Gilbert syndrome (UGT1A1*28/*28) and associated hyperbilirubinemia but not cholelithiasis in adolescent and adult north Indian patients with transfusion-dependent β-thalassemia. Ann Hematol 2020; 99:2019-2026. [PMID: 32676731 DOI: 10.1007/s00277-020-04176-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 07/09/2020] [Indexed: 11/30/2022]
Abstract
Hyperbilirubinemia and pigment gallstones are frequent complications in transfusion-dependent β-thalassemia (TDβT) patients. Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis, hemolysis, infection-induced hepatic injury, and drug- or iron-related toxicities. We studied the frequency of the Gilbert syndrome (GS), a common hereditary cause of hyperbilirubinemia in 102 TDβT patients aged 13-43 years (median 26 years). Total and unconjugated hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either alanine or aspartate aminotransferase, or alkaline phosphatase liver enzymes. Nineteen (18.6% of the 92 tested) were positive for hepatitis B or C, or HIV. The mean total and unconjugated bilirubin levels and AST, ALT, and ALP levels in patients positive for hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had gallstones. There was no significant difference in total/unconjugated bilirubin in patients with/without gallstones and no significant differences in frequencies of gallstones within the three UGT1A1 genotypes. This largest study in Indian TDβT patients suggests that GS should be excluded in TDβT cases where jaundice remains unexplained after treatable causes like infections, chelator toxicity, or transfusion-related hemolysis are excluded. GS was not associated with gallstones, possibly due to a lower incidence of cholelithiasis overall, a younger age cohort, or other environmental factors.
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Affiliation(s)
- Oshan Shrestha
- Pathology Group of Departments, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Alka Rani Khadwal
- Department of Internal Medicine, Adult Clinical Hematology Unit, PGIMER, Chandigarh, India
| | - Manphool Singhal
- Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh, India
| | - Amita Trehan
- Department of Pediatric Medicine, Pediatric Hematology/Oncology Unit, PGIMER, Chandigarh, India
| | - Deepak Bansal
- Department of Pediatric Medicine, Pediatric Hematology/Oncology Unit, PGIMER, Chandigarh, India
| | - Richa Jain
- Department of Pediatric Medicine, Pediatric Hematology/Oncology Unit, PGIMER, Chandigarh, India
| | - Arnab Pal
- Department of Biochemistry, PGIMER, Chandigarh, India
| | - Jasbir Kaur Hira
- Department of Hematology, PGIMER, Level 5, Research Block A, Sector 12, Chandigarh, 160012, India
| | - Sanjeev Chhabra
- Department of Hematology, PGIMER, Level 5, Research Block A, Sector 12, Chandigarh, 160012, India
| | - Pankaj Malhotra
- Department of Internal Medicine, Adult Clinical Hematology Unit, PGIMER, Chandigarh, India
| | - Reena Das
- Department of Hematology, PGIMER, Level 5, Research Block A, Sector 12, Chandigarh, 160012, India
| | - Prashant Sharma
- Department of Hematology, PGIMER, Level 5, Research Block A, Sector 12, Chandigarh, 160012, India.
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Carubbi F, Cappellini MD, Fargion S, Fracanzani AL, Nascimbeni F. Liver involvement in Gaucher disease: A practical review for the hepatologist and the gastroenterologist. Dig Liver Dis 2020; 52:368-373. [PMID: 32057684 DOI: 10.1016/j.dld.2020.01.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 01/02/2020] [Accepted: 01/12/2020] [Indexed: 02/06/2023]
Abstract
Gaucher disease (GD), a rare lysosomal storage disorder caused by deficient glucocerebrosidase activity and consequent accumulation of glycosphingolipids in the mononuclear phagocyte system, may progress to disabling and potentially life-threatening complications when left undiagnosed and untreated. Unfortunately, because of non-specific signs and symptoms and lack of awareness, patients with type 1 GD, the most common non-neuropathic variant, frequently experience diagnostic delays. Since splenomegaly and thrombocytopenia are the dominant clinical features in many GD patients leading to first medical contact, the hepatologist and the gastroenterologist need to be aware of this condition. Liver involvement has been reported in the majority of GD patients, and comprises hepatomegaly, with or without liver enzymes alteration, fibrosis/cirrhosis, portal hypertension, focal liver lesions, and cholelithiasis. Moreover, GD is associated with several biochemical alterations of potential interest for the hepatologist and the gastroenterologist, including hypergammaglobulinemia, hyperferritinemia and metabolic abnormalities, that may lead to misdiagnoses with chronic liver diseases of common etiology, such as primary hemochromatosis, autoimmune liver diseases or nonalcoholic fatty liver disease. This comprehensive review, based on the collaborative experience of physicians managing patients with GD, provides practical information on the clinical, histological and radiological hepatic manifestations of GD aiming at facilitating the diagnosis of GD for the hepatologist and the gastroenterologist.
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Affiliation(s)
- Francesca Carubbi
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy.
| | - Maria Domenica Cappellini
- Rare Diseases Center, Department of Medicine, "Ca' Granda" Foundation IRCCS, Policlinico Hospital, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Silvia Fargion
- "Ca' Granda" Foundation IRCCS, Policlinico Hospital, University of Milan, Milan, Italy
| | - Anna Ludovica Fracanzani
- "Ca' Granda" Foundation IRCCS, Policlinico Hospital, University of Milan, Milan, Italy; Department of Pathophysiology and Transplantation, Unit of Medicine and Metabolic Disorders, Milan, Italy
| | - Fabio Nascimbeni
- Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU of Modena, University of Modena and Reggio Emilia, Modena, Italy
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Abstract
OBJECTIVE The objective of this article was to demonstrate that Gaucher disease (GD) patients with refractory hypersplenism and massive splenomegaly may successfully undergo hand-assisted laparoscopic splenectomy (HALS). METHODS This was a retrospective audit conducted at the Gaucher clinic at a national referral center over a 10-year period. PATIENT POPULATION This study included 8 GD patients who underwent hand-assisted or conventional laparoscopic splenectomy for massive or complicated splenomegaly between the years 2007 and 2017. RESULTS Seven patients underwent an elective HALS procedure because of refractory hypersplenism, whereas 1 patient underwent an urgent conventional laparoscopic splenectomy because of torsion of a wandering spleen. Only 1 patient required conversion to open surgery because of multiple adhesions from a previous partial splenectomy. The mean weight of the removed spleens was 2373 g (range, 480 to 4900 g), mean craniocaudal length of the removed spleens was 25 cm (range, 20 to 33.5 cm), and mean operating time was 150 minutes (range, 96 to 280 min). Postoperative complications were limited to 2 patients and included thrombosis of the splenic vein stump in 1 patient, and propagation of a preoperative splenic vein thrombus to the portal system, as well as an accumulation of an intra-abdominal hematoma in another patient. There was no mortality. Mean length of hospital stay was 5 days (range, 2 to 11 d). CONCLUSION HALS for GD patients with refractory hypersplenism and massive splenomegaly is safe and feasible in experienced hands.
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Adar T, Ilan Y, Elstein D, Zimran A. Liver involvement in Gaucher disease – Review and clinical approach. Blood Cells Mol Dis 2018; 68:66-73. [DOI: 10.1016/j.bcmd.2016.10.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 10/17/2016] [Indexed: 02/07/2023]
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Case report of cholelithiasis in a patient with type 1 Gaucher disease. Int J Surg Case Rep 2016; 29:227-229. [PMID: 27915213 PMCID: PMC5137175 DOI: 10.1016/j.ijscr.2016.11.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 11/06/2016] [Accepted: 11/06/2016] [Indexed: 11/21/2022] Open
Abstract
Case report of cholelithiasis in a patient with type 1 Gaucher disease; which is very intriguing to show this comorbidity. The case was the only known case with this pathology in time of diagnosis in our country (Kosovo). Thus, gallstones and cholecystitis should be considered when abdominal symptoms and liver dysfunctions are seen in these patients. More studies are needed to determine the incidence and prevalence of gallstones in Gaucher disease patients in especially Kosovo. Introduction Patients with type 1 Gaucher disease have been reported to be more likely to have cholelithiasis. Presentation of case A case of cholelithiasis in a patient with type 1 Gaucher disease; which is very intriguing to show this comorbidity. The case was the only known case with this pathology in time of diagnosis in our country (Kosovo). The patient is a 21-year old girl a known case of type 1 Gaucher disease, at the age of 8 years. The patient underwent elective laparoscopic cholecystectomy. Chronic inflammatory changes and adhesions were obvious during surgery. Discussion Type 1 Gaucher disease patients have several risk factors for gallstone formation: increased biliary excretion of glucosylceramide, advanced liver disease and cirrhosis, splenomegaly, inborn error of metabolism, chronic systemic inflammation, T cell dysfunction, and insulin resistance” to risk factors. Conclusion Gallstones and cholecystitis should be considered when abdominal symptoms and liver dysfunctions are seen in these patients. More studies are needed in especially Kosovo.
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Abstract
Abstract
This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the “one enzyme–one disease–one therapy” mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified.
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Lee HJ, Moon HS, Lee ES, Kim SH, Sung JK, Lee BS, Jeong HY, Lee HY, Eu YJ. A case of concomitant Gilbert's syndrome and hereditary spherocytosis. THE KOREAN JOURNAL OF HEPATOLOGY 2011; 16:321-4. [PMID: 20924216 PMCID: PMC3304593 DOI: 10.3350/kjhep.2010.16.3.321] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilbert's syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene.
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Affiliation(s)
- Hee Jung Lee
- Department of Internal Medicine, School of Medicine, Chungnam National University, School of Medicine, Daejeon, Korea
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An unusual form of Gaucher’s disease: pulmonary and cardiovascular involvement and cholelitiasis. Open Med (Wars) 2010. [DOI: 10.2478/s11536-009-0062-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
AbstractGaucher’s disease is an inherited storage disease caused by a deficiency of the enzyme glucocerebrosidase. Although the hepatic manifestations are seen frequently, pulmonary and cardiovascular involvements are known to be very rare in Gaucher’s disease. This report presents these rare findings made by conventional radiography, computerized tomography (CT), and High-resolution CT (HRCT) of a 16-year-old female patient with fatal Gaucher’s disease.
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Taddei TH, Dziura J, Chen S, Yang R, Hyogo H, Sullards C, Cohen DE, Pastores G, Mistry PK. High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease. J Inherit Metab Dis 2010; 33:291-300. [PMID: 20354791 PMCID: PMC3008397 DOI: 10.1007/s10545-010-9070-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2009] [Revised: 01/14/2010] [Accepted: 02/15/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND In Gaucher disease (GD), lysosomal glucocerebrosidase deficiency results in glucosylceramide accumulation in macrophage lysosomes. Hepatocytes do not accumulate glucosylceramide due in part to biliary secretion. Although gallstones (GS) occur in type 1 Gaucher disease (GD1), the chemical nature of stones, their association with metabolic parameters, and whether bile composition is altered are not understood. We assessed the prevalence of GS, their chemical composition, biliary lipids, and associated metabolic factors. METHODS The study cohort comprised 417 patients comprehensively evaluated for GD1 severity. Ascertainment of GS, fasting lipoprotein profile, and bile lipid analyses were performed. RESULTS The prevalence of GS in GD1 was 32%. Compared with men, the prevalence of GS was higher in women, increasing from 4.2% and 11.8% at age 20-29 years to 71% and 60% at age >70 years, respectively. Patients with GS were more likely to be asplenic (p < 0.0001), older (p < 0.0001), have higher low-density lipoprotein (LDL) cholesterol (p = 0.002), and more severe GD1 disease compared with those without GS. On multiple logistic regression analysis, factors associated with GS were age (p < 0.001), female sex (p = 0.03), and splenectomy (p = 0.005). Compared with the general population, prevalence of GS was approximately 5-fold higher. Bile lipid analyses revealed cholesterol stones in five patients and pigment stones in one. Bile lipid composition was abnormal and contained glucosylceramide. CONCLUSIONS Our results point to a metabolic syndrome in GD1 consisting of a propensity to cholesterol GS, low high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and body mass index (BMI) associated with abnormal biliary lipid secretion.
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Affiliation(s)
- Tamar H. Taddei
- Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA
| | - James Dziura
- Department of Biostatistics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA
| | - Shu Chen
- Department of Biostatistics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA
| | - Ruhua Yang
- Department of Pediatrics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA
| | - Hideyuki Hyogo
- Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Cameron Sullards
- Bioanalytical Mass Spectrometry Facility, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, GA 30332-0363, USA
| | - David E. Cohen
- Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, USA
| | | | - Pramod K. Mistry
- Department of Pediatrics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA. Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA. Pediatric Hepatology and Gastroenterology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06562, USA
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Grigorescu-Sido P, Drugan C, Alkhzouz C, Zimmermann A, Coldea C, Denes C, Grigorescu MD, Cret V, Bucerzan S. Baseline characteristics and outcome in Romanian patients with Gaucher disease type 1. Eur J Intern Med 2010; 21:104-13. [PMID: 20206881 DOI: 10.1016/j.ejim.2009.11.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2009] [Revised: 10/25/2009] [Accepted: 11/15/2009] [Indexed: 11/28/2022]
Abstract
BACKGROUND/AIM To present clinical and genetic characteristics of all Romanian patients with Gaucher disease type 1, in whom specific diagnosis has been confirmed by enzymatic and molecular methods and to analyze their outcome with and without enzymatic replacement therapy (ERT). PATIENTS, METHODS There are fifty patients (F/M - 1.63/1) with Gaucher disease type 1. Clinical status, haemoglobin, thrombocytes, hepatic/splenic volume, bone mineral density and severity score were assessed at baseline and every six months thereafter. Thirty-nine patients (78%) received imiglucerase (44.4+/-13.6 U/kg/2 weeks) for 3.1+/-1.4 years. RESULTS Based on general prevalence data, our group represents 22.7% of the expected total number of patients with Gaucher disease type 1 in Romania. Mean age was 15.5 years at clinical onset and 28.9 years at confirmation of diagnosis. The genotype N370S/L444P was frequent in our group (35.9% of alleles). Anaemia, thrombocytopenia, splenomegaly and bone disease were present at 38%, 70%, 100% and 84%, respectively. Mean values for haemoglobin, thrombocytes, hepatic volume and chitotriosidase normalized after 0.5, 1.5, 2.5 and 3 years of ERT, respectively. Splenomegaly regressed from 14.4 x N (normal) to 3.06 x N over four years of treatment. Bone disease was ameliorated under ERT, yet bone mineral density worsened in patients treated with 30 U/kg/2 weeks. CONCLUSIONS The genotype N370S/L444P is frequent in our patients, in line with the severe phenotypes. ERT improved haematological parameters and visceromegaly, without a clear benefit for bone mineral density. To attain therapeutic goals, an early treatment start with optimal dosage is mandatory.
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Affiliation(s)
- Paula Grigorescu-Sido
- 1st Pediatric Clinic, Center of Genetic Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj, Romania
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Abstract
Gaucher disease (GD) is an autosomal recessive disease which if undiagnosed or diagnosed late results in devastating complications. Because of the heterozygous nature of GD, there is a wide spectrum of clinical presentation. Clinicians should be aware of this rare but potentially treatable disease in patients who present with unexplained organomegaly, anemia, massive splenomegaly, ascites and even cirrhosis of unknown origin. The treatment options for adult type GD include enzyme replacement treatment (ERT) and substrate reduction treatment (SRT) depending on the status of the patient. Future treatment options are gene therapy and “smart molecules” which provide specific cure and additional treatment options. In this review, we present the key issues about GD and new developments that gastroenterologists should be aware of.
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Raja M, Azzoni A, Giona F, Regis S, Grossi S, Filocamo M, Sidransky E. Movement and mood disorder in two brothers with Gaucher disease. Clin Genet 2007; 72:357-61. [PMID: 17850633 DOI: 10.1111/j.1399-0004.2007.00863.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Gaucher disease (GD) is a lysosomal storage disorder with a wide spectrum of phenotypic presentations. We report the case histories of two adult brothers with GD who developed both parkinsonism and psychiatric symptoms. Direct sequencing and real-time polymerase chain reaction were used to establish that the patients were homozygous for mutation L444P. While parkinsonism has been described previously in GD, these patients had atypical features, including a complicated mood disorder. The comorbidity of GD and a mood disorder is a new finding, as psychiatric manifestations of GD have been described rarely. The etiology of the mental illness could be related to the processes contributing to the development of parkinsonism.
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Affiliation(s)
- M Raja
- Servizio Psichiatrico di Diagnosi e Cura, Ospedale Santo Spirito, Rome, Italy
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