The fraternal twin sisters are presenting with episodes of fasting hypoglycemia, hypoketonemia, and muscle weakness occurring only during periods of calorific deprivation. One twin dies at 5 months of age. The surviving twin develops a cardiomyopathy, which is diagnosed at 3 years of age. Carnitine esters are elevated in muscle tissue and in serum. Which of the following is the most likely diagnosis?

Each of the genetic deficiencies listed may present with cardiomyopathy in childhood. LCAD affects the first step in b-oxidation of fatty acids in the mitochondria. Cardiac muscle and resting skeletal muscle use fatty acids and ketones as a primary energy source, thus in LCAD deficiency, muscle weakness and eventually cardiomyopathy develop. Fasting hypoglycemia and hypoketosis occurring together are strongly suggestive of a block in fatty acid oxidation. Only a carnitine uptake deficiency (choice : Carnitine uptake deficiency) or LCAD deficiency (choice : LCAD) are related to fatty acid oxidation. Since carnitine esters (long chain acyl carnitines) are accumulating in serum and in muscle tissue, a carnitine uptake deficiency is ruled out. a-L-Iduronidase deficiency, or Hurler disease (choice : a-L-Iduronidase deficiency) is another of the lysosomal storage diseases. Cardiomyopathy, valvular defects, and potential occlusion of coronary aeries, are results of specific glycosaminoglycan (heparan sulfate and dermatan sulfate) accumulation. Similar substrate accumulation in other tissues results in corneal clouding, mental retardation, and skeletal abnormalities. Hypoglycemia, hypoketosis, and muscle weakness are not prominent features of Hurler disease. There would be no accumulation of carnitine derivatives. Acid maltase is a lysosomal enzyme, and its deficiency produces one of a host of lysosomal storage diseases. Acid maltase deficiency (a 1,4-glucosidase deficiency; choice : Acid maltase deficiency) or Pompe disease is also associated with cardiomyopathy. In this case glycogen fragments accumulate in the lysosomes, primarily affecting tissues that store glycogen (muscle, liver, kidney). Hypoglycemia and hypoketosis are not features of this deficiency, nor would acyl carnitines accumulate.