Dataset Information

Case report: Familial glycogen storage disease type IV caused by novel compound heterozygous mutations in a glycogen branching enzyme 1 gene.

ABSTRACT: Glycogen storage disease type IV (GSD IV), caused by a mutation in the glycogen branching enzyme 1 (GBE1) gene, is a rare metabolic disorder with an autosomal recessive inheritance that involves the liver, neuromuscular, and cardiac systems. Here, we reported a case of familial GSD IV induced by novel compound heterozygous mutations in GBE1. The proband (at age 1) and her younger brother (at age 10 months) manifested hepatosplenomegaly, liver dysfunction, and growth retardation at onset, followed by progressive disease deterioration to liver cirrhosis with liver failure. During the disease course, the proband presented rare intractable asymptomatic hypoglycemia. The liver pathology was in line with GSD IV. Both cases carried pathogenic compound heterozygous mutations in GBE1 mutations, i.e., a missense mutation (c.271T>A, p. W91R) in exon 2 and a deletion mutation in partial exons 3-7. Both mutations are first reported. The internationally pioneered split-liver transplantation was performed during progression to end-stage liver disease, and the patients had normal liver function and blood glucose after. This study broadens the mutation spectrum of the GBE1 gene and the phenotypic spectrum of GSD IV.

SUBMITTER: Li Y

PROVIDER: S-EPMC9679404 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Case report: Familial glycogen storage disease type IV caused by novel compound heterozygous mutations in a glycogen branching enzyme 1 gene.

Li Yiyang Y Tian Chuan C Huang Si S Zhang Weijie W Liutang Qiuyu Q Wang Yajun Y Ma Guoda G Chen Riling R

Frontiers in genetics 20221108

Glycogen storage disease type IV (GSD IV), caused by a mutation in the glycogen branching enzyme 1 (GBE1) gene, is a rare metabolic disorder with an autosomal recessive inheritance that involves the liver, neuromuscular, and cardiac systems. Here, we reported a case of familial GSD IV induced by novel compound heterozygous mutations in GBE1. The proband (at age 1) and her younger brother (at age 10 months) manifested hepatosplenomegaly, liver dysfunction, and growth retardation at onset, followe ...[more]

PMID: 36425069

Similar Datasets

Project description:RationaleGlycogen storage disease (GSD) is a glycogen metabolism disorder caused by congenital enzyme defects, with type I being the most common. Owing to the rarity of glycogen storage disease type Ia (GSD Ia) and the involvement of diverse systems, patients are prone to delayed diagnosis and inappropriate treatment. Additional studies are required to standardize the diagnosis and treatment of GSD Ia.Patient concernsWe report 2 cases of GSD Ia that occurred in 2 sisters. The elder sister also had recurrent pancreatitis, and the pancreatic pseudocyst rupture resulted in sepsis, portal hypertension, and splenic infarction. The younger sister had the same mutation site, but the clinical phenotypes were not identical.DiagnosisAbdominal computed tomography and laboratory examinations revealed regional portal hypertension, splenic infarction, and sepsis in the elder sister; diagnosis was confirmed by whole exome sequencing. Sanger sequencing was used to confirm that the younger sister and their parents also had the mutation site.InterventionsThe elder sister was treated with corn starch therapy, and medication for antiinfection and reducing hypertriglyceridemia, inhibiting trypsin activity, relieving hyperuricemia. The younger sister was treated with raw cornstarch-based nutritional therapy and sodium bicarbonate.OutcomesThe elder sister's infection was controlled and she gradually returned to a normal diet. After discharge, hyperlipidemia was not controlled satisfactorily, but hypoglycemia, hyperuricemia, hyperlactatemia, and anemia improved.LessonsGSD should be considered in childhood patients with hypoglycemia, hypertriglyceridemia, hyperuricemia, and hyperlactatemia. Gene sequencing can enable quick identification of GSD subtypes. This case report highlights the common clinical manifestations can be linked to rare diseases. Clinical work requires careful observation of the correlations between patient history, physical examinations, and laboratory examinations.

Project description:In bacteria, glycogen plays important roles in carbon and energy storage. Its structure has recently been linked with bacterial environmental durability. Among the essential genes for bacterial glycogen metabolism, the glgB-encoded branching enzyme GBE plays an essential role in forming α-1,6-glycosidic branching points, and determines the unique branching patterns in glycogen. Previously, evolutionary analysis of a small sets of GBEs based on their N-terminal domain organization revealed that two types of GBEs might exist: (1) Type 1 GBE with both N1 and N2 (also known as CBM48) domains and (2) Type 2 GBE with only the N2 domain. In this study, we initially analyzed N-terminal domains of 169 manually reviewed bacterial GBEs based on hidden Markov models. A previously unreported group of GBEs (Type 3) with around 100 amino acids ahead of the N1 domains was identified. Phylogenetic analysis found clustered patterns of GBE types in certain bacterial phyla, with the shorter, Type 2 GBEs predominantly found in Gram-positive species, while the longer Type 1 GBEs are found in Gram-negative species. Several in vitro studies have linked N1 domain with transfer of short oligosaccharide chains during glycogen formation, which could lead to small and compact glycogen structures. Compact glycogen degrades more slowly and, as a result, may serve as a durable energy reserve, contributing to the enhanced environmental persistence for bacteria. We were therefore interested in classifying GBEs based on their N-terminal domain via large-scale sequence analysis. In addition, we set to understand the evolutionary patterns of different GBEs through phylogenetic analysis at species and sequence levels. Three-dimensional modeling of GBE N-termini was also performed for structural comparisons. A further study of 9,387 GBE sequences identified 147 GBEs that might belong to a possibly novel group of Type 3 GBE, most of which fall into the phylum of Actinobacteria. We also attempted to correlate glycogen average chain length (ACL) with GBE types. However, no significant conclusions were drawn due to limited data availability. In sum, our study systematically investigated bacterial GBEs in terms of domain organizations from evolutionary point of view, which provides guidance for further experimental study of GBE N-terminal functions in glycogen structure and bacterial physiology.

Dataset Information

Case report: Familial glycogen storage disease type IV caused by novel compound heterozygous mutations in a glycogen branching enzyme 1 gene.

Publications

Case report: Familial glycogen storage disease type IV caused by novel compound heterozygous mutations in a glycogen branching enzyme 1 gene.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets