A 5-month-old boy is brought to the office due to poor feeding. His mother says that he has difficulty holding his head up while breastfeeding and his suckling seems weaker than usual. Weight is at the 5th percentile. Length and head circumference are tracking along the 25th percentile. Physical examination shows hepatomegaly and hypotonia in all 4 limbs. Cardiac auscultation shows a gallop rhythm, and chest x-ray reveals severe cardiomegaly. Muscle biopsy shows enlarged lysosomes containing periodic acid-Schiff (PAS)-positive material. Which of the following enzymes is most likely deficient in this patient?

Question

A 5-month-old boy is brought to the office due to poor feeding.  His mother says that he has difficulty holding his head up while breastfeeding and his suckling seems weaker than usual.  Weight is at the 5th percentile.  Length and head circumference are tracking along the 25th percentile.  Physical examination shows hepatomegaly and hypotonia in all 4 limbs.  Cardiac auscultation shows a gallop rhythm, and chest x-ray reveals severe cardiomegaly.  Muscle biopsy shows enlarged lysosomes containing periodic acid-Schiff (PAS)-positive material.  Which of the following enzymes is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_36a2_2568_9249_1b67dfe8f6b5_MD0001_00 This patient most likely has glycogen storage disease type II (Pompe disease). This condition is caused by deficiency of acid alpha-glucosidase (alpha-1,4 glucosidase or acid maltase), an enzyme responsible for breaking down glycogen within the acidic environment of lysosomes. Although most glycogen is degraded in the cytoplasm, a small percentage is inadvertently engulfed by lysosomes, especially in cells containing high amounts of glycogen such as hepatocytes and myocytes. Deficiency of acid maltase results in pathologic accumulation of glycogen within liver and muscle lysosomes. Cardiac and skeletal muscle are particularly susceptible because the ballooning lysosomes interfere with contractile function. The classic form of the disease presents in early infancy with marked cardiomegaly, severe generalized hypotonia, macroglossia, and hepatomegaly. Blood glucose levels are normal, unlike with glycogen storage diseases that primarily affect the liver (eg, von Gierke disease). A key distinguishing feature is that muscle biopsy will show accumulation of glycogen in lysosomes. (Choice B) Galactokinase catalyzes the phosphorylation of galactose to galactose-1-phosphate in the first committed step of galactose catabolism. Galactokinase deficiency causes neonatal cataract formation due to accumulation of galactitol in the lens. (Choices C, D, and E) Other glycogen storage diseases are caused by deficiencies of glucose-6-phosphatase, glycogen phosphorylase, and glycogen debrancher enzyme (debranching enzyme). However, glycogen accumulation within lysosomal vacuoles is specific for acid alpha-glucosidase deficiency. (Choice F) Pyruvate kinase deficiency causes chronic hemolytic anemia, splenomegaly, and iron overload as a result of impaired erythrocyte survival. Educational objective: Acid maltase (alpha-glucosidase) deficiency presents in early infancy with cardiomegaly, macroglossia, and profound muscular hypotonia. Abnormal glycogen accumulation within lysosomal vesicles is seen on muscle biopsy. __________ References: Lysosomal dysfunction in muscle with special reference to glycogen storage disease type II. (http://www.ncbi.nlm.nih.gov/pubmed/12633905)

A 5-Month-Old Boy Is Brought to the Office Due to Poor