We report a 2-year-old boy with Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GK) and adrenal hypoplasia congenita (AHC). At three weeks of age, the patient was hospitalized for the first time with symptoms of hypotone dehydration because of AHC. At present, he shows severe muscular hypotonia and developmental delay. The patient and his family were referred to us for prenatal diagnosis and carrier testing in the mother of the patient and the mother's sister, respectively. The patient's DNA was examined by Southern blot and polymerase chain reaction analyses, using cDNA and genomic probes within and around the dystrophin (DYS) locus. A deletion was revealed, spanning DXS28, the whole dystrophin locus, DXS84 and DXS148, whereas DXS67, DXS68 (pter) and OTC (cen) were found to be retained. The cytogenetically visible microdeletion was also seen in the patient's mother, but not in the mother's sister or the patient's maternal grandmother. Our findings support the locus order pter-DXS67-DXS68-DXS28-AHC-GK-DMD-cen.
The localisation of the relevant genes within the Xp21 region of the short arm of the X chromosome has been shown by cytogenetic analysis of individuals with these disorders (Wieringa et al. 1985); the locus order Xpter-AHC-GK-DMD-Xcen has now been established (Davies et al. 1988)
Case report
The patient was first hospitalized at the age of three weeks with symptoms of hypotone dehydration (Na 122 mEq/l, K 5.8 mEq/l). AHC was diagnosed and then treated with corticosteroid hormones. At a later stage, developmental delay, severe muscular hypotonia, an elevated serum creatine kinase (CK) level (5698 mU/ml) and a muscular biopsy specimen showing degenerative changes typical of muscular dystrophy led to the diagnosis of DMD. Finally, the diagnosis GK was confirmed by elevated glycerol levels in serum and urine (Prof. Steinmann, Ztirich). Ocular symptoms have not been assessed.
There is no family history of this microdeletion syndrome. The patients mother shows a mild mental retardation but no other clinical indications; all other family members are clinically normal.