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1
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Tanaka A, Ogawa M, Zhou Y, Hendrickson RC, Miele MM, Li Z, Klimstra DS, Wang JY, Roehrl MHA. Proteomic basis for pancreatic acinar cell carcinoma and pancreatoblastoma as similar yet distinct entities. NPJ Precis Oncol 2024; 8:221. [PMID: 39363045 PMCID: PMC11449907 DOI: 10.1038/s41698-024-00708-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 09/12/2024] [Indexed: 10/05/2024] Open
Abstract
Acinar cell carcinoma (ACC) and pancreatoblastoma (PBL) are rare pancreatic malignancies with acinar differentiation. Proteogenomic profiling of ACC and PBL revealed distinct protein expression patterns compared to pancreatic ductal adenocarcinoma (PDAC) and benign pancreas. ACC and PBL exhibited similarities, with enrichment in proteins related to RNA processing, chromosome organization, and the mitoribosome, while PDACs overexpressed proteins associated with actin-based processes, extracellular matrix, and immune-active stroma. Pathway activity differences in metabolic adaptation, epithelial-to-mesenchymal transition, and DNA repair were characterized between these diseases. PBL showed upregulation of Wnt-CTNNB1 and IGF2 pathways. Seventeen ACC-specific proteins suggested connections to metabolic diseases with mitochondrial dysfunction, while 34 PBL-specific proteins marked this pediatric cancer with an embryonic stem cell phenotype and alterations in chromosomal proteins and the cell cycle. This study provides novel insights into the proteomic landscapes of ACC and PBL, offering potential targets for diagnostic and therapeutic development.
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Affiliation(s)
- Atsushi Tanaka
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Makiko Ogawa
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Yihua Zhou
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- ICU Department, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ronald C Hendrickson
- Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Matthew M Miele
- Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Zhuoning Li
- Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David S Klimstra
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Paige.AI, New York, NY, USA
| | | | - Michael H A Roehrl
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Schuster-Little N, McCabe M, Nenninger K, Safavi-Sohi R, Whelan RJ, Hilliard TS. Generational Diet-Induced Obesity Remodels the Omental Adipose Proteome in Female Mice. Nutrients 2024; 16:3086. [PMID: 39339686 PMCID: PMC11435095 DOI: 10.3390/nu16183086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/16/2024] [Accepted: 08/27/2024] [Indexed: 09/30/2024] Open
Abstract
Obesity, a complex condition that involves genetic, environmental, and behavioral factors, is a non-infectious pandemic that affects over 650 million adults worldwide with a rapidly growing prevalence. A major contributor is the consumption of high-fat diets, an increasingly common feature of modern diets. Maternal obesity results in an increased risk of offspring developing obesity and related health problems; however, the impact of maternal diet on the adipose tissue composition of offspring has not been evaluated. Here, we designed a generational diet-induced obesity study in female C57BL/6 mice that included maternal cohorts and their female offspring fed either a control diet (10% fat) or a high-fat diet (45% fat) and examined the visceral adipose proteome. Solubilizing proteins from adipose tissue is challenging due to the need for high concentrations of detergents; however, the use of a detergent-compatible sample preparation strategy based on suspension trapping (S-Trap) enabled label-free quantitative bottom-up analysis of the adipose proteome. We identified differentially expressed proteins related to lipid metabolism, inflammatory disease, immune response, and cancer, providing valuable molecular-level insight into how maternal obesity impacts the health of offspring. Data are available via ProteomeXchange with the identifier PXD042092.
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Affiliation(s)
- Naviya Schuster-Little
- Department of Chemistry, University of Kansas, Lawrence, KS 66045, USA; (N.S.-L.); (R.J.W.)
- Ralph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047, USA
| | - Morgan McCabe
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; (M.M.); (K.N.); (R.S.-S.)
| | - Kayla Nenninger
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; (M.M.); (K.N.); (R.S.-S.)
| | - Reihaneh Safavi-Sohi
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; (M.M.); (K.N.); (R.S.-S.)
- Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46617, USA
- Department of Chemistry and Biochemistry, Seton Hall University, South Orange, NJ 07079, USA
| | - Rebecca J. Whelan
- Department of Chemistry, University of Kansas, Lawrence, KS 66045, USA; (N.S.-L.); (R.J.W.)
- Ralph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047, USA
| | - Tyvette S. Hilliard
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; (M.M.); (K.N.); (R.S.-S.)
- Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46617, USA
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Garbowski L, Walasek M, Firszt R, Chilińska-Kopko E, Błażejewska-Gała P, Popielnicki D, Dzięcioł-Anikiej Z. A Case Study of a Rare Disease (Fructosemia) Diagnosed in a Patient with Abdominal Pain. J Clin Med 2024; 13:3394. [PMID: 38929922 PMCID: PMC11204229 DOI: 10.3390/jcm13123394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 05/22/2024] [Accepted: 05/29/2024] [Indexed: 06/28/2024] Open
Abstract
Hereditary fructose intolerance is a rare genetic disorder that is inherited in an autosomal recessive manner, with mutations sometimes occurring spontaneously. Consuming fructose triggers biochemical abnormalities, disrupting liver processes like glycogenolysis and gluconeogenesis. Recent studies have revealed elevated intrahepatic fat levels in affected individuals. Symptoms include aversion to fructose-containing foods, hypoglycemia, liver and kidney dysfunction, and growth delays, with severe cases leading to liver enlargement, fatty liver disease, kidney failure, and life-threatening hypoglycemia. In this case study, we present a 20-month-old child with symptoms including difficulty passing stool, abdominal rigidity, abdominal pain with bloating and hypoglycemia. Initial clinical findings revealed elevated liver enzymes, a mildly enlarged hyperechoic liver, hypercholesterolemia, and borderline alpha-fetoprotein values. Diagnostic assessments identified hereditary fructose intolerance (HFI) with pathogenic variants in the ALDOB gene, along with a diagnosis of celiac disease. Genetic testing of the parents revealed carrier status for pathological aldolase B genes. This case underscores the importance of comprehensive clinical evaluation and genetic testing in pediatric patients with complex metabolic presentations.
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Affiliation(s)
- Leszek Garbowski
- Public Independent Healthcare Services of the Ministry of Internal Affairs and Administration in Białystok, 15-471 Białystok, Poland
- Department of Human Anatomy, Medical University of Białystok, 15-089 Białystok, Poland (P.B.-G.); (D.P.)
| | - Marzena Walasek
- Public Independent Healthcare Services of the Ministry of Internal Affairs and Administration in Białystok, 15-471 Białystok, Poland
| | - Rafał Firszt
- Department of Ornamental Plants and Garden Art, Faculty of Biotechnology and Horticulture, University of Agriculture in Krakow, 31-425 Kraków, Poland;
| | - Ewelina Chilińska-Kopko
- Department of Human Anatomy, Medical University of Białystok, 15-089 Białystok, Poland (P.B.-G.); (D.P.)
| | - Paulina Błażejewska-Gała
- Department of Human Anatomy, Medical University of Białystok, 15-089 Białystok, Poland (P.B.-G.); (D.P.)
- Department of Neonatology and Newborn Intensive Care, University Clinical Hospital in Białystok, 15-276 Białystok, Poland
| | - Daniel Popielnicki
- Department of Human Anatomy, Medical University of Białystok, 15-089 Białystok, Poland (P.B.-G.); (D.P.)
| | - Zofia Dzięcioł-Anikiej
- Department of Rehabilitation, University Clinical Hospital in Białystok, 15-276 Białystok, Poland
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Panis B, Janssen LEF, Lefeber DJ, Simons N, Rubio‐Gozalbo ME, Brouwers MCGJ. Development of tools to facilitate the diagnosis of hereditary fructose intolerance. JIMD Rep 2023; 64:353-359. [PMID: 37701328 PMCID: PMC10494505 DOI: 10.1002/jmd2.12379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/15/2023] [Accepted: 06/20/2023] [Indexed: 09/14/2023] Open
Abstract
Although hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism that classically presents at infancy, the diagnosis is often missed or delayed. In this study, we aimed to develop tools to facilitate the diagnosis of HFI. The intake of fructose-containing food products, that is, fruit, fruit juice and sugar-sweetened beverages, was assessed by a 3-day food diary in adult HFI patients (n = 15) and age, sex, and BMI-matched controls (n = 15). Furthermore, glycosylation of transferrin was examined using high-resolution mass spectrometry and abnormally glycosylated transferrin was expressed as ratio of normal glycosylated transferrin. We found that the sensitivity and specificity of the 3-day food diary for the intake of at least one fructose-containing food product were both 100%. Both mono-glyco:diglyco transferrin and a-glyco+mono-glyco:di-glyco transferrin were greater in HFI patients and had a high-discriminatory power (area under the receiver operating characteristic curve: 0.97 and 0.94, respectively). In this well-characterized cohort of adult HFI patients, the 3-day food questionnaire and the glycosylation pattern of transferrin are valuable tools to facilitate the recognition and diagnosis of HFI in adult patients.
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Affiliation(s)
- Bianca Panis
- Division of Genetic Metabolic Diseases, Department of PediatricsMaastricht University Medical CenterMaastrichtThe Netherlands
- Member of European Reference Network for Hereditary Metabolic Diseases (MetabERN)
- Member of United for Metabolic Diseases (UMD)
| | - Lise E. F. Janssen
- Division of Endocrinology and Metabolic Diseases, Department of Internal MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
| | - Dirk J. Lefeber
- Translational Metabolic Laboratory, Department of Laboratory MedicineRadboud University Medical CenterNijmegenThe Netherlands
- Department of NeurologyRadboud University Medical CenterNijmegenThe Netherlands
| | - Nynke Simons
- Division of Endocrinology and Metabolic Diseases, Department of Internal MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
- Laboratory for Metabolism and Vascular Medicine, Division of General Internal Medicine, department of Internal MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
- CARIM, School for Cardiovascular DiseasesMaastrichtThe Netherlands
| | - M. Estela Rubio‐Gozalbo
- Division of Genetic Metabolic Diseases, Department of PediatricsMaastricht University Medical CenterMaastrichtThe Netherlands
- Member of European Reference Network for Hereditary Metabolic Diseases (MetabERN)
- Member of United for Metabolic Diseases (UMD)
- Department of Clinical GeneticsMaastricht University Medical Center, Maastricht UniversityMaastrichtThe Netherlands
- GROW‐School for Oncology and Developmental Biology, Faculty of Health, Medicine and Life SciencesMaastricht UniversityMaastrichtThe Netherlands
| | - Martijn C. G. J. Brouwers
- Member of European Reference Network for Hereditary Metabolic Diseases (MetabERN)
- Member of United for Metabolic Diseases (UMD)
- Division of Endocrinology and Metabolic Diseases, Department of Internal MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
- Laboratory for Metabolism and Vascular Medicine, Division of General Internal Medicine, department of Internal MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
- CARIM, School for Cardiovascular DiseasesMaastrichtThe Netherlands
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Wittwer J, Beveridge G, Klein L, Thomsen K, Gigante J. Food Selectivity, Rash, and Leg Pain in a 7-year-old Boy with Malnutrition. Pediatr Rev 2023; 44:232-235. [PMID: 37002358 PMCID: PMC10474899 DOI: 10.1542/pir.2021-005047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2023]
Affiliation(s)
| | | | - Lauren Klein
- D. Brent Polk Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN
| | - Kelly Thomsen
- D. Brent Polk Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN
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Tang M, Chen X, Ni Q, Lu Y, Wu B, Wang H, Yin Z, Zhou W, Dong X. Estimation of hereditary fructose intolerance prevalence in the Chinese population. Orphanet J Rare Dis 2022; 17:326. [PMID: 36028839 PMCID: PMC9419342 DOI: 10.1186/s13023-022-02487-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 08/15/2022] [Indexed: 11/15/2022] Open
Abstract
Background Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency that results in fructose metabolism disorder. The disease prevalence in the Chinese population is unknown, which impedes the formulation of HFI screening and diagnosis strategies. Materials and methods By searching a local cohort (Chinese Children’s Rare Disease Genetic Testing Clinical Collaboration System, CCGT) and public databases (ClinVar and Human Gene Mutation Database) and reviewing HFI-related literature, we manually curated ALDOB pathogenic or likely pathogenic (P/LP) variants according to ACMG guidelines. Allele frequency (AF) information from the local database CCGT and the public databases HuaBiao and gnomAD for ALDOB P/LP variants was used to estimate and the HFI prevalence in the Chinese population and other populations by the Bayesian framework. We collected the genotype and clinical characteristics of HFI patients from the CCGT database and published literature to study genotype–phenotype relationships. Result In total, 81 variants of ALDOB were curated as P/LP. The estimated Chinese HFI prevalence was approximately 1/504,678, which was much lower than that for non-Finland European (1/23,147), Finnish in Finland (1/55,539), admixed American (1/132,801) and Ashkenazi Jewish (1/263,150) populations. By analyzing the genetic characteristics of ALDOB in the Chinese population, two variants (A338V, A338G) had significantly higher AFs in the Chinese population than in the non-Finland European population from gnomAD (all P values < 0.05). Five variants (A150P, A175D, N335K, R60*, R304Q) had significantly lower AFs (all P values < 0.1). The genotype–phenotype association analyses were based on 68 reported HFI patients from a literature review and the CCGT database. The results showed that patients carrying homozygous variant sites (especially A150P) were more likely to present nausea, and patients carrying two missense variant sites were more likely to present aversion to sweets and fruit (all P values < 0.05). Our research reveals that some gastrointestinal symptoms seem to be associated with certain genotypes. Conclusion The prevalence of HFI in the Chinese population is extremely low, and there is no need to add HFI testing to the current newborn screening programs if medical costs are considered. A genetic testing strategy is suggested for early diagnosis of HFI. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-022-02487-3.
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Affiliation(s)
- Meiling Tang
- Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Xiang Chen
- Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Qi Ni
- Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Yulan Lu
- Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Bingbing Wu
- Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Huijun Wang
- Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China
| | - Zhaoqing Yin
- Department of Pediatrics, Dehong Hospital of Kunming Medical University, Dehong, 678400, China
| | - Wenhao Zhou
- Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China.
| | - Xinran Dong
- Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China.
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7
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Singh SK, Sarma MS. Hereditary fructose intolerance: A comprehensive review. World J Clin Pediatr 2022; 11:321-329. [PMID: 36052111 PMCID: PMC9331401 DOI: 10.5409/wjcp.v11.i4.321] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 05/08/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
Hereditary fructose intolerance (HFI) is a rare autosomal recessive inherited disorder that occurs due to the mutation of enzyme aldolase B located on chromosome 9q22.3. A fructose load leads to the rapid accumulation of fructose 1-phosphate and manifests with its downstream effects. Most commonly children are affected with gastrointestinal symptoms, feeding issues, aversion to sweets and hypoglycemia. Liver manifestations include an asymptomatic increase of transaminases, steatohepatitis and rarely liver failure. Renal involvement usually occurs in the form of proximal renal tubular acidosis and may lead to chronic renal insufficiency. For confirmation, a genetic test is favored over the measurement of aldolase B activity in the liver biopsy specimen. The crux of HFI management lies in the absolute avoidance of foods containing fructose, sucrose, and sorbitol (FSS). There are many dilemmas regarding tolerance, dietary restriction and occurrence of steatohepatitis. Patients with HFI who adhere strictly to FSS free diet have an excellent prognosis with a normal lifespan. This review attempts to increase awareness and provide a comprehensive review of this rare but treatable disorder.
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Affiliation(s)
- Sumit Kumar Singh
- Department of Pediatrics, Sri Aurobindo Medical College and PGI, Indore 453555, Madhya Pradesh, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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Pinheiro FC, Sperb-Ludwig F, Schwartz IVD. Epidemiological aspects of hereditary fructose intolerance: A database study. Hum Mutat 2021; 42:1548-1566. [PMID: 34524712 DOI: 10.1002/humu.24282] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 09/05/2021] [Accepted: 09/11/2021] [Indexed: 12/11/2022]
Abstract
Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism of autosomal recessive inheritance caused by pathogenic variants in the ALDOB gene that lead to aldolase B deficiency in the liver, kidneys, and intestine. Patients manifest symptoms, such as ketotic hypoglycemia, vomiting, nausea, in addition to hepatomegaly and other liver and kidney dysfunctions. The treatment consists of a fructose-restricted diet, which results in a good prognosis. To analyze the distribution of ALDOB variants described in patients and to estimate the prevalence of HFI based on carrier frequency in the gnomAD database, a systematic review was conducted to assess ALDOB gene variants among patients with HFI. The prevalence of HFI was estimated from the carrier frequency of variants described in patients, as well as rare variants predicted as pathogenic by in silico tools. The p.(Ala150Pro) and p.(Ala175Asp) variants are the most frequent and are distributed worldwide. However, these variants have particular distribution patterns in Europe. The analysis of the prevalence of HFI showed that the inclusion of rare alleles predicted as pathogenic is a more informative approach for populations with few patients. The data show that HFI has a wide distribution and an estimated prevalence of ~1:10,000.
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Affiliation(s)
- Franciele C Pinheiro
- Post-Graduate Program in Genetics and Molecular Biology, Federal University of do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,BRAIN Laboratory, Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.,Federal University of Pampa, Itaqui, Rio Grande do Sul, Brazil
| | - Fernanda Sperb-Ludwig
- Post-Graduate Program in Genetics and Molecular Biology, Federal University of do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,BRAIN Laboratory, Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Ida V D Schwartz
- Post-Graduate Program in Genetics and Molecular Biology, Federal University of do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,BRAIN Laboratory, Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.,Department of Genetics, Bioscience Institute, Federal University of do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.,Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
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9
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Fructose and Mannose in Inborn Errors of Metabolism and Cancer. Metabolites 2021; 11:metabo11080479. [PMID: 34436420 PMCID: PMC8397987 DOI: 10.3390/metabo11080479] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 07/21/2021] [Accepted: 07/21/2021] [Indexed: 12/19/2022] Open
Abstract
History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.
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Lee J, Arenth J, Kasi N. Neonatal Hereditary Fructose Intolerance: Diagnostic Misconceptions and the Role of Genomic Sequencing. JPGN REPORTS 2021; 2:e076. [PMID: 37207065 PMCID: PMC10191584 DOI: 10.1097/pg9.0000000000000076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 02/24/2021] [Indexed: 05/21/2023]
Abstract
Hereditary fructose intolerance (HFI) is a rare inborn error of metabolism due to deficiency of the enzyme aldolase B, preventing metabolism of fructose. Patients remain asymptomatic until exposed to fructose, sucrose, or sorbitol. HFI presenting as acute liver failure in the neonatal period is rare due to lack of exposure as breast milk and infant formulas are considered to be fructose free. Diagnosis can be delayed due to vague symptoms and lack of specific biomarkers. Recent advances in genetic testing have led to rapid diagnosis and favorable outcomes. We present the case of a formula-fed neonate who presented with acute liver failure where definitive diagnosis of HFI was made using expedited whole exome sequencing. Through this communication, we aim to bring attention to neonatal presentations of HFI from exposure to fructose in infant formulas and also highlight advances in rapid turnaround genomic testing in diagnosis.
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Affiliation(s)
- Jeffrey Lee
- From the Division of Pediatric Gastroenterology and Hepatology, Medical University of South Carolina, Shawn Jenkins Children’s Hospital, Charleston, SC
| | - Joshua Arenth
- Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Shawn Jenkins Children’s Hospital, Charleston, SC
| | - Nagraj Kasi
- From the Division of Pediatric Gastroenterology and Hepatology, Medical University of South Carolina, Shawn Jenkins Children’s Hospital, Charleston, SC
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