Full expression of Hunter's disease in a female with an X-chromosome deletion leading to non-random inactivation

Abstract

A 2.5‐year‐old girl who presented with abdominal distension, hepatomegaly, coarse fades, hirsutism and contraction deformities was investigated for mucopolysaccharidoses. Urinary excretion showed increased total glycosaminoglycans (105 mg/mmol creatinine; normal for age 9–20 mg/mmol) with marked increases of dermatan and heparan sulphates. A number of lysosomal enzyme activities were measured on leucocytes, serum and cultured fibroblasts. Normal or high activities were found for a‐iduronidase, N‐acetylgalactosamine‐6‐sulphatase, β‐galactosidase, arylsulphatase B and /J‐glucuronidase. However a marked deficiency ofiduronate sulphate sulphatase activity was observed, consistent with a diagnosis of Hunter's disease. Activities were reduced to less than 2% of mean control values in the patient's leucocytes, serum and cultured fibroblasts. Normal activities were measured in samples from the father and younger sister but a partial deficiency (43% of control serum) was found in the mother. Chromosome studies on the patient revealed a partial deletion of the long arm of one X‐chromosome, most probably of band Xq25, which was not inherited from either parent. Studies using BrdU indicated that the deleted X chromosome was consistently late replicating, and as a result the Hunter gene was fully expressed on the other X chromosome.