Lesch-Nyhan syndrome in a girl

Lesch-Nyhan syndrome (McKusick 308000) is characterized by hyperuricaemia, choreoathetosis, spasticity, mental retardation, and self-mutilation. This disorder results from a complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), an enzyme encoded by a single gene on the X chromosome (Xq26-q27) (Stout and Caskey 1989), and has already been identified in a female patient (Ogasawara et al 1989). We report a second case of a female Lesch-Nyhan patient. This girt was born from healthy non-consanguineous parents and had a healthy brother and sister. The circumstances of her birth were normal (weight 2720 g after 37 weeks of gestation; APGAR score at 10 after 1 min), but a transient hypoglycaemic episode was noticed on her first day of life. Hypotonia and developmental retardation appeared in her first months of life. Three febrile convulsive episodes occurred between 18 and 36 months of life. Self-mutilation of her fingers occurred when she was 4 years old and still persisted when we saw her at 7 years of age. Weight and height were three standard deviations below the normal range, but cranial circumference was in the normal range. There were severe biting lesions of her finger extremities. On neurological examination, the girl had excellent social contact but her language was dysarthic and poor for age. Examination of the cranial nerves was normal. A spastic quadriparesis was present, making the sitting position impossible without support. Prehension of objects was acquired but was dystonic and clumsy. There were no sensory disturbances. Electroencephalogram and cranial computed tomographic scan were unremarkabte. Hyperuricaemia (467 #tool/L) and elevated 24-h urinary uric acid to creatinine ratio (1.1) were consistent with HPRT deficiency, which was confirmed by measurement of enzyme activity in erythrocytes (0.11 nmol min-1 (mg haemoglobin)-1) for the patient, the normal value for our laboratory being 2.09 _+ 0.37). The karyotype was 46 XX and no morphological abnormalities could be identified by a high-resolution analysis of the chromosomes. In the case described by Ogasawara et al (1989), a Southern analysis of DNA identified a deletion that involved the entire HPRT gene and was not found in the parents. Furthermore, these authors showed that this de novo mutation occurred on the maternal X-chromosome; so it was concluded that there had been non-random inactivation of the cytologically normal paternal X-chromosome. We tried to determine the carrier status of our patient's mother by using cultured fibroblasts, since it has been demonstrated that obligate heterozygotes are mosaics