A 6-month-old girl is brought to the office by her mother for a checkup appointment. The mother states, "My baby doesn't seem to be growing much despite feeding as often as my previous children. I am worried that something is wrong with her." Physical examination shows hepatomegaly, hypotonia, and height and weight below the 10th percentile. Laboratory studies show hypoglycemia and ketoacidosis. A liver biopsy shows hepatic fibrosis without fat accumulation. Further analysis reveals abundant quantities of a multibranched polysaccharide with abnormally short outer chains within the cytosol of the hepatocytes. Which of the following enzymes is most likely deficient in this patient?

Question

A 6-month-old girl is brought to the office by her mother for a checkup appointment.  The mother states, "My baby doesn't seem to be growing much despite feeding as often as my previous children.  I am worried that something is wrong with her."  Physical examination shows hepatomegaly, hypotonia, and height and weight below the 10th percentile.  Laboratory studies show hypoglycemia and ketoacidosis.  A liver biopsy shows hepatic fibrosis without fat accumulation.  Further analysis reveals abundant quantities of a multibranched polysaccharide with abnormally short outer chains within the cytosol of the hepatocytes.  Which of the following enzymes is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_36a2_9a99_9249_3351366ac3dd_MD0001_00 Debranching enzyme deficiency (Cori disease) usually presents in infancy or childhood with both liver and muscle involvement. Symptoms include hypoglycemia, hepatomegaly, and ketoacidosis. Muscle weakness and hypotonia help to distinguish the condition from other glycogen storage diseases with hepatic involvement (eg, von Gierke, Hers). Hepatic fibrosis is common, but fatty infiltration is not usually seen. A key distinguishing feature is cytosolic accumulation of glycogen with abnormally short outer chains (limit dextrins). During glycogenolysis, glycogen phosphorylase shortens glycogen chains by cleaving α-1,4-glycosidic linkages between glucose residues, liberating glucose-1-phosphate in the process. This occurs until 4 residues remain before a branch point (the limit dextrin). At this point, debranching enzyme performs 2 enzymatic functions: (Choice A) Small amounts of glycogen are broken down by the lysosomal enzyme acid maltase (has both α-1,4- and α-1,6-glucosidase activity). Acid maltase deficiency (Pompe disease) is characterized by cardiomegaly, severe generalized hypotonia, and lysosomal glycogen accumulation (hypoglycemia is not seen). (Choice C) Glucose-6-phosphatase deficiency (von Gierke disease) affects mainly the liver and kidney, as the enzyme is not expressed in significant quantities in muscle tissue. Major symptoms include hypoglycemia, lactic acidosis, hyperlipidemia, and hyperuricemia. Hepatic steatosis is a cardinal manifestation of the disorder. (Choice D) Liver glycogen phosphorylase deficiency (Hers disease) presents in early childhood with mild hypoglycemia, ketosis, and hepatomegaly. However, it does not affect skeletal muscles and would show an excess of normally structured glycogen (not limit dextrins) on liver biopsy. (Choice E) Muscle glycogen phosphorylase deficiency causes McArdle disease, a condition that presents with decreased exercise tolerance, muscle pain and cramping during strenuous activity, and myoglobinuria. Blood lactate is often very low after exercise, and muscle biopsy shows an excess of normally structured glycogen. (Choice F) Pyruvate kinase converts phosphoenolpyruvate to pyruvate during glycolysis. Pyruvate kinase deficiency causes chronic hemolytic anemia as glycolysis is the main source of energy for erythrocytes. Educational objective: Debranching enzyme deficiency (Cori disease) leads to accumulation of glycogen with abnormally short outer chains (limit dextrins) due to the inability to degrade α-1,6-glycosidic branch points. Patients present with hypoglycemia, ketoacidosis, hepatomegaly, and muscle weakness and hypotonia.

A 6-Month-Old Girl Is Brought to the Office by Her