A 4-month-old girl with a 1-month history of poor head control and progressive muscle weakness is brought to the physician for a follow-up examination. Physical signs show a large tongue, hepatomegaly, and severe generalized hypotonia. A chest x-ray shows cardiomegaly. She dies of cardiac failure at the age of 10 months. Autopsy shows a markedly enlarged globular heart, hepatomegaly, and glycogen in the skeletal muscle, heart, and liver. This patient most likely had a deficiency in which of the following?

Question

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The infant is suffering from glycogen storage disease type III (GSDIII), which is also known as Cori disease, Forbes disease, or limit dextrinosis. This GSD results from defects in the gene encoding glycogen debrancher enzyme, also known as amylo- 1,6-glucosidase. Deficiency in glycogen debranching activity causes hepatomegaly, ketotic hypoglycemia, hyperlipidemia, variable skeletal myopathy, cardiomyopathy, and results in short stature. Patients with both liver and muscle involvement have GSDIIIa and those with only liver involvement (~15% of GSDIII patients) are classified as GSDIIIb. Because heptomegaly, hypoglycemia, hyperlipidemia, and growth retardation are common symptoms in both GSDI and GSDIII, it is difficult to initially determine from which disease an infant is suffering. Definitive diagnosis is only made by examining the structure of the glycogen in patients as well as assaying for the level of activity of the debranching enzyme.

A 4-Month-Old Girl with a 1-Month History of Poor Head