TY - JOUR
T1 - Glycogen storage disease type I
T2 - Diagnosis and phenotype/genotype correlation
AU - Matern, Dietrich
AU - Seydewitz, Hans Hermann
AU - Bali, Deeksha
AU - Lang, Christine
AU - Chen, Yuan Tsong
PY - 2002
Y1 - 2002
N2 - Glycogen storage disease type Ia (GSD Ia) is caused by mutations in the G6PC gene encoding the phosphatase of the microsomal glucose-6-phosphatase system. GSD Ia is characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia and short stature. Other forms of GSD I (GSD I non-a) are characterized by the additional symptom of frequent infections caused by neutropenia and neutrophil dysfunction. GSD I non-a is caused by mutations in a gene encoding glucose-6-phosphatase translocase (G6PT1). We report on the molecular genetic analyses of G6PC and G6PT1 in 130 GSD Ia patients and 15 GSD I non-a patients, respectively, and provide an overview of the current literature pertaining to the molecular genetics of GSD I. Among the GSD Ia patients, 34 different mutations were identified, two of which have not been described before (A65P; F177C). Seventeen different mutations were detected in the GSD I non-a patients. True common mutations were identified neither in GSD Ia nor in GSD I non-a patients. Conclusion: Glycogen storage disease type Ia and and type I non-a are genetically heterogenous disorders. For the diagnosis of the various forms of glycogen storage disease type I, molecular genetic analyses are reliable and convenient alternatives to the enzyme assays in liver biopsy specimens. Some genotype-phenotype correlations exist, for example, homozygosity for one G6PC mutation, G188R, seems to be associated with a glycogen storage disease type I non-a phenotype and homozygosity for the 727G > T mutation may be associated with a milder phenotype but an increased risk for hepatocellular carcinoma.
AB - Glycogen storage disease type Ia (GSD Ia) is caused by mutations in the G6PC gene encoding the phosphatase of the microsomal glucose-6-phosphatase system. GSD Ia is characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia and short stature. Other forms of GSD I (GSD I non-a) are characterized by the additional symptom of frequent infections caused by neutropenia and neutrophil dysfunction. GSD I non-a is caused by mutations in a gene encoding glucose-6-phosphatase translocase (G6PT1). We report on the molecular genetic analyses of G6PC and G6PT1 in 130 GSD Ia patients and 15 GSD I non-a patients, respectively, and provide an overview of the current literature pertaining to the molecular genetics of GSD I. Among the GSD Ia patients, 34 different mutations were identified, two of which have not been described before (A65P; F177C). Seventeen different mutations were detected in the GSD I non-a patients. True common mutations were identified neither in GSD Ia nor in GSD I non-a patients. Conclusion: Glycogen storage disease type Ia and and type I non-a are genetically heterogenous disorders. For the diagnosis of the various forms of glycogen storage disease type I, molecular genetic analyses are reliable and convenient alternatives to the enzyme assays in liver biopsy specimens. Some genotype-phenotype correlations exist, for example, homozygosity for one G6PC mutation, G188R, seems to be associated with a glycogen storage disease type I non-a phenotype and homozygosity for the 727G > T mutation may be associated with a milder phenotype but an increased risk for hepatocellular carcinoma.
KW - Diagnosis
KW - Glucose-6-phosphatase
KW - Glucose-6-phosphate translocase
KW - Glycogen storage disease type I
KW - Molecular genetics
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U2 - 10.1007/bf02679989
DO - 10.1007/bf02679989
M3 - Article
C2 - 12373566
AN - SCOPUS:0036392426
SN - 0943-9676
VL - 161
SP - S10-S19
JO - European Journal of Pediatrics, Supplement
JF - European Journal of Pediatrics, Supplement
IS - 1
ER -