title: Congenital muscular dystrophy syndromes distinguished by alkaline and acid phosphatase, merosin, and dystrophin staining.
abstract: 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.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Connolly
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: G J
authors.initials: GJ
authors.lastname: Planer
authors.forename: J
authors.initials: J
authors.lastname: Yue
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: R
authors.initials: R
authors.lastname: Choksi
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism*; D000293:Adolescent; D000469:Alkaline Phosphatase / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016189:Dystrophin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007797:Laminin / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000378:metabolism; D009136:Muscular Dystrophies / Q000151:congenital* / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D013194:Staining and Labeling; D013577:Syndrome
chemical_list: D016189:Dystrophin; D007797:Laminin; C084098:laminin A; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase