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.

Molecular analysis of iduronate -2- sulfatase gene in Tunisian patients with mucopolysaccharidosis type II

“…Furthermore, MPS II is expected to be found only in males, but some females have been reported [25,26]. …”

Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease

“…They are typically heterozygous for this X-linked disorder and most are asymptomatic 'carriers' with normal or slightly reduced I2S activity [3]. Some heterozygous females have been found to develop signs and symptoms because of structural abnormalities of the × chromosome or skewed inactivation of the paternal × chromosome [7,8,21-25]. There has also been one report of a female patient who was homozygous for a disease-causing point mutation [9].…”

Clinical and biochemical studies in mucopolysaccharidosis type II carriers

“…Full expression of MPS II in females is very rare (to our knowledge, about 10 cases have been reported to date) and is secondary to the presence of either pathogenic mutations in both alleles of the IDS gene (Cudry et al 2000) or non-random inactivation of the X chromosome in heterozygotes or in carriers of structural X-chromosome abnormality (Broadhead et al 1986;Clarke et al 1990;Cudry et al 2000;Mossman et al 1983;Neufeld et al 1977;Sukegawa et al 1997Sukegawa et al , 1998Tuschl et al 2005;Winchester et al 1992).…”