Clinical, Biochemical, and Genetic Characterization of Glycogen Storage Type IX in a Child with Asymptomatic Hepatomegaly.
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SUBMITTER: Kim JA
PROVIDER: S-EPMC4493248 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
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Clinical, Biochemical, and Genetic Characterization of Glycogen Storage Type IX in a Child with Asymptomatic Hepatomegaly.
Kim Jung Ah JA Kim Ja Hye JH Lee Beom Hee BH Kim Gu-Hwan GH Shin Yoon S YS Yoo Han-Wook HW Kim Kyung Mo KM
Pediatric gastroenterology, hepatology & nutrition 20150629 2
Glycogen storage disease type IX (GSD IX) is caused by a defect in phosphorylase b kinase (PhK) that results from mutations in the PHKA2, PHKB, and PHKG2 genes. Patients usually manifest recurrent ketotic hypoglycemia with growth delay, but some may present simple hepatomegaly. Although GSD IX is one of the most common causes of GSDs, its biochemical and genetic diagnosis has been problematic due to its rarity, phenotypic overlap with other types of GSDs, and genetic heterogeneities. In our repo ...[more]
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Project description:BackgroundGlycogen storage disease type 1a (GSD1a) is a rare autosomal recessive metabolic disorder characterized by hypoglycaemia, growth retardation, lactic acidosis, hepatomegaly, hyperlipidemia, and nephromegaly. GSD1a is caused by a mutation in the G6PC gene encoding glucose-6-phosphatase (G6Pase); an enzyme that catalyses the hydrolysis of glucose-6-phosphate (G6P) to phosphate and glucose.ObjectiveTo elaborate on the clinical findings, biochemical data, molecular genetic analysis, and short-term prognosis of 13 GSD1a patients in Malaysia.MethodsThe information about 13 clinically classified GSD1a patients was retrospectively studied. The G6PC mutation analysis was performed by PCR-DNA sequencing.ResultsPatients were presented with hepatomegaly (92%), hypoglycaemia (38%), poor weight gain (23%), and short stature (15%). Mutation analysis revealed nine heterozygous mutations; eight previously reported mutations (c.155 A > T, c.209 G > A, c.226 A > T, c.248 G > A, c.648 G > T, c.706 T > A, c.1022 T > A, c.262delG) and a novel mutation (c.325 T > C). The most common mutation found in Malaysian patients was c.648 G > T in ten patients (77%) of mostly Malay ethnicity, followed by c.248 G > A in 4 patients of Chinese ethnicity (30%). A novel missense mutation (c.325 T > C) was predicted to be disease-causing by various in silico software.ConclusionsThe establishment of G6PC molecular genetic testing will enable the detection of presymptomatic patients, assisting in genetic counselling while avoiding the invasive methods of liver biopsy.
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Project description:BACKGROUND:According to the textbooks, the ketotic glycogen storage disease (GSD) types 0, III, VI, IX, and XI are associated with fasting ketotic hypoglycemia and considered milder as gluconeogenesis is intact. METHODS:A retrospective cohort study of biochemical profiles from supervised clinical fasting studies is performed in ketotic GSD patients in our metabolic center. For data analysis, hypoglycemia was defined as plasma glucose concentration <2.6 mmol/L. Total KB was defined as the sum of blood acetoacetate and ?-hydroxybutyrate concentrations. If the product of glucose and KB concentrations was greater than 10, a ketolysis defect was suspected. RESULTS:Data could be collected from 13 fasting studies in 12 patients with GSD III (n?=?4), GSD VI (n?=?3), and GSD IX (n?=?5). Six patients remained normoglycemic with median glucose concentration of 3.9 mmol/L (range, 2.8-4.6 mmol/L) and median total KB concentration of 1.9 mmol/L (range, 0.6-5.1 mmol/L). The normoglycemic patients included type VI (3 out of 3) and type IX (3 out of 5) patients. All type III patients developed ketotic hypoglycemia. Interestingly, in five patients (one GSD III, one GSD VI, and three GSD IX), the biochemical profile suggested a ketolysis defect. CONCLUSION:Normoglycemic ketonemia is a common biochemical presentation in patients with GSD types VI and IX, and ketonemia can precede hypoglycemia in all studied GSD types. Therefore, GSD VI and GSD IX should be added to the differential diagnosis of ketotic normoglycemia, and KB concentrations should be routinely measured in ketotic GSD patients.
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