Duchenne muscular dystrophy with adrenal insufficiency and glycerol kinase deficiency: high resolution cytogenetic analysis with molecular, biochemical, and clinical studies.

A syndrome of Duchenne muscular dystrophy (DMD), adrenal hypoplasia, glycerol kinase deficiency, and mental retardation has been recognised. We report a further case ascertained from a history of DMD, severe mental retardation, and an Addison-like disorder. Cytogenetic analysis of the proband revealed an interstitial deletion of the short arm of the X chromosome. from Xp21.1 to Xp22.11, comprising about 9% of the length of the normal X chromosome. His mother was heterozygous for the deletion, but his maternal grandmother and sister both had two normal X chromosomes. DNA probe analysis confirmed the existence of a deletion in the affected boy, as probes 754, C7, XJ1-1, and pERT87 consistently failed to hybridize to his DNA. His sister was heterozygous for the RFLP associated with 754, thus confirming that she had two normal X chromosomes. There was no evidence of chronic granulomatous disease, other immunological defect, or retinitis pigmentosa in this case. Biochemical studies revealed gross glyceroluria and hyperglycerolaemia, indicating glycerol kinase deficiency which has been confirmed enzymatically. We have subsequently screened 21 other boys with DMD for glyceroluria and found one other case. Cytogenetic analysis has also been performed in nine other families, where a boy with DMD has been shown to have a deletion of DNA sequences localised to the region Xp21. None of these cases demonstrated any cytogenetic abnormality, nor has their clinical course been unusual.