Congenital muscular dystrophy syndromes distinguished by alkaline and acid phosphatase, merosin, and dystrophin staining.

Congenital muscular dystrophy syndromes are characterized by congenital weakness, contractures, and dystrophic features on muscle biopsy. However, these syndromes are often difficult to diagnose precisely because their clinical and pathologic characteristics are not specific and resemble changes in other myopathies. We examined muscle biopsies from 20 children with a congenital muscular dystrophy syndrome. Disease controls with dystrophies or other myopathies (n=19) and normal individuals (n=15) were studied for comparison. In each biopsy we determined (1) numbers of muscle fibers with alkaline phosphatase (AlkP) staining, (2) numbers of acid phosphatase-(AcP) positive cells, (3) dystrophin levels by immunocytochemistry, and (4) the distribution of merosin and laminin-A staining. A ratio of AcP:AlkP staining was calculated for each biopsy. In nine patients with congenital muscular dystrophy (younger than 4 years of age) with normal dystrophin, the AcP:AlkP ratio was low (0.09 +/- 0.03). In contrast, in Duchenne muscular dystrophy, the AcP:AlkP ratio was 15 times higher (1.6 +/- 0.04, p=0.001). The three children with congetial muscular dystrophy syndromes and reduced dystrophin and one child with facioscapulohumeral dystrophy had AcP:AlkP ratios in the range of Duchenne muscular dystrophy patients (2.4 +/- 1.4). Low Ac:AlkP ratios were related to relative absence of AcP-positive cells. Merosin staining was absent in 5 of the 17 congenital muscular dystrophy biopsies tested. None of the 5 children with merosin-negative but all 12 with merosin-positive stains walked (p=0.0002). We conclude that a pattern of few AcP-positive cells in the setting of numerous AlkP staining muscle fibers has specificity for congenital muscular dystrophy syndromes and provides histopathologic support for the diagnosis. Reduced merosin in muscle predicts more severe weakness and long-term disability.

McArdle's disease with myoadenylate deaminase deficiency: observations in a combined enzyme deficiency.

Exercise and work potential of a patient with coexistent myophosphorylase and myoadenylate deaminase (AMPDA) deficiency was compared with that of three patients with myophosphorylase deficiency alone. The patient with the combined defect failed to produce an abnormal rise in serum ammonia or hypoxanthine as seen in the other patients after forearm exercise. Maximum oxygen consumption and work rates during cycle ergometer testing were similar in all patients, but well below controls. The occurrence of two defects involving short-term energy metabolism in muscle presents an opportunity to define further the metabolic role of AMPDA.

Activity, creatine kinase, and myoglobin in Duchenne muscular dystrophy: a clue to etiology?

Large and seemingly random fluctuations in the serum levels of creatine kinase (CK) and myoglobin (Mb) have been noted in patients with Duchenne muscular dystrophy. We studied seven affected boys, aged 2 to 9 years. Blood was drawn for CK and Mb every 4 hours, and the boys' activity was documented hourly for 4 days. There was a close correlation between serum levels of CK and Mb with physical activity. Fluctuations in serum levels of CK and Mb are not random and may result from an abnormality of fatty acid metabolism.

Fasting as a provocative test in neuromuscular diseases.

A 38-hr fast was used as a provocative test in patients suspected of having defects in muscle substrate utilization. In five controls and nine patients, exercise capacity and respiratory exchange ratio were determined before and at the end of the fast. Blood was collected at intervals during the fast from ten controls and nine patients for creatine kinase (CK), free fatty acids, (FFA) beta-hydroxybutyrate, acetoacetate, free and total carnitine, glucose, and alanine. Two patients with myophosphorylase deficiency had increased exercise capacity, and a marked fall in CK, and one had a lesser fall in blood glucose than normal at the end of the fast. Two patients with known lipid myopathies (carnitine deficiency and carnitine palmityl transferase deficiency) had decreased exercise capacity and apparent increased dependence on carbohydrate metabolism during the fast. Carnitine concentrations became even more abnormal in the patient with carnitine deficiency during fasting. Several patients with less well-defined defects were also significantly different from the controls in several respects, indicating that the fast might be useful for finding new defects.