Glycogen storage disease type IV: Novel mutations and molecular characterization of a heterogeneous disorder

Sing Chung Li, Chiao-Ming Chen, Jennifer L. Goldstein, Jer Yuarn Wu, Emmanuelle Lemyre, Thomas Andrew Burrow, Peter B. Kang, Yuan Tsong Chen, Deeksha S. Bali

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterization of underlying disease-causing mutations is now possible. A variety of disease-causing mutations have been identified in the GBE1 gene in GSD IV patients, many of whom presented with diverse clinical phenotypes. Detailed biochemical and genetic analyses of three unrelated patients suspected to have GSD IV are presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations in GBE1 have been previously reported, including missense and nonsense mutations, nucleotide deletions and insertions, and donor and acceptor splice-site mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV-especially when higher residual GBE enzyme activity levels are seen and enzyme analysis is not definitive-And allows for further determination of potential genotype/phenotype correlations in this disease.

Original languageEnglish
JournalJournal of Inherited Metabolic Disease
Volume33
Issue numberSUPPL. 3
DOIs
Publication statusPublished - 2010

Fingerprint

Glycogen Storage Disease Type IV
Mutation
1,4-alpha-Glucan Branching Enzyme
RNA Splice Sites
Missense Mutation
Glycogen
Amylopectin
Nonsense Codon
Sequence Deletion
Genetic Association Studies
Enzymes
Age of Onset
Liver Cirrhosis
Solubility
Genes
Organism Cloning
Molecular Biology
Nucleotides
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Glycogen storage disease type IV : Novel mutations and molecular characterization of a heterogeneous disorder. / Li, Sing Chung; Chen, Chiao-Ming; Goldstein, Jennifer L.; Wu, Jer Yuarn; Lemyre, Emmanuelle; Burrow, Thomas Andrew; Kang, Peter B.; Chen, Yuan Tsong; Bali, Deeksha S.

In: Journal of Inherited Metabolic Disease, Vol. 33, No. SUPPL. 3, 2010.

Research output: Contribution to journalArticle

Li, Sing Chung ; Chen, Chiao-Ming ; Goldstein, Jennifer L. ; Wu, Jer Yuarn ; Lemyre, Emmanuelle ; Burrow, Thomas Andrew ; Kang, Peter B. ; Chen, Yuan Tsong ; Bali, Deeksha S. / Glycogen storage disease type IV : Novel mutations and molecular characterization of a heterogeneous disorder. In: Journal of Inherited Metabolic Disease. 2010 ; Vol. 33, No. SUPPL. 3.
@article{05f078c8bb44479997a80fd0878a2f2e,
title = "Glycogen storage disease type IV: Novel mutations and molecular characterization of a heterogeneous disorder",
abstract = "Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterization of underlying disease-causing mutations is now possible. A variety of disease-causing mutations have been identified in the GBE1 gene in GSD IV patients, many of whom presented with diverse clinical phenotypes. Detailed biochemical and genetic analyses of three unrelated patients suspected to have GSD IV are presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations in GBE1 have been previously reported, including missense and nonsense mutations, nucleotide deletions and insertions, and donor and acceptor splice-site mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV-especially when higher residual GBE enzyme activity levels are seen and enzyme analysis is not definitive-And allows for further determination of potential genotype/phenotype correlations in this disease.",
author = "Li, {Sing Chung} and Chiao-Ming Chen and Goldstein, {Jennifer L.} and Wu, {Jer Yuarn} and Emmanuelle Lemyre and Burrow, {Thomas Andrew} and Kang, {Peter B.} and Chen, {Yuan Tsong} and Bali, {Deeksha S.}",
year = "2010",
doi = "10.1007/s10545-009-9026-5",
language = "English",
volume = "33",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "SUPPL. 3",

}

TY - JOUR

T1 - Glycogen storage disease type IV

T2 - Novel mutations and molecular characterization of a heterogeneous disorder

AU - Li, Sing Chung

AU - Chen, Chiao-Ming

AU - Goldstein, Jennifer L.

AU - Wu, Jer Yuarn

AU - Lemyre, Emmanuelle

AU - Burrow, Thomas Andrew

AU - Kang, Peter B.

AU - Chen, Yuan Tsong

AU - Bali, Deeksha S.

PY - 2010

Y1 - 2010

N2 - Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterization of underlying disease-causing mutations is now possible. A variety of disease-causing mutations have been identified in the GBE1 gene in GSD IV patients, many of whom presented with diverse clinical phenotypes. Detailed biochemical and genetic analyses of three unrelated patients suspected to have GSD IV are presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations in GBE1 have been previously reported, including missense and nonsense mutations, nucleotide deletions and insertions, and donor and acceptor splice-site mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV-especially when higher residual GBE enzyme activity levels are seen and enzyme analysis is not definitive-And allows for further determination of potential genotype/phenotype correlations in this disease.

AB - Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterization of underlying disease-causing mutations is now possible. A variety of disease-causing mutations have been identified in the GBE1 gene in GSD IV patients, many of whom presented with diverse clinical phenotypes. Detailed biochemical and genetic analyses of three unrelated patients suspected to have GSD IV are presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations in GBE1 have been previously reported, including missense and nonsense mutations, nucleotide deletions and insertions, and donor and acceptor splice-site mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV-especially when higher residual GBE enzyme activity levels are seen and enzyme analysis is not definitive-And allows for further determination of potential genotype/phenotype correlations in this disease.

UR - http://www.scopus.com/inward/record.url?scp=77958157941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958157941&partnerID=8YFLogxK

U2 - 10.1007/s10545-009-9026-5

DO - 10.1007/s10545-009-9026-5

M3 - Article

C2 - 20058079

AN - SCOPUS:77958157941

VL - 33

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - SUPPL. 3

ER -