Heterozygous expression of Lesch-Nyhan syndrome clinical and ultrastructural studies

The study comprised two cases (male & female sibs) from one family, with Lesch-Nyhan Syndrome. They were subjected to clinical evaluation, pedigree construction, uric acid estimation in blood, urates in urine, metabolic screening of blood and urine for amino acids, examination of oral cavity, histological studies of the gingiva by light and electron microscopy as well as buccal smear for Barr & Y bodies (for the female). The proband, a six years old female presented with self-mutilation, mental retardation, hyperactivity and aggression. She had bitten her index finger causing amputation of its distal phalanx. On family study her younger brother (9 months) was found to have increased uric acid and less severe neurologic involvement. The serum uric acid level of the affected female was higher. Her Barr body showed normal pattern. Oral cavity examination showed no abnormalities. Histological examination of the gingiva showed macrophages around the blood vessels. Ultrastructural studies showed more or less normal epithelium. There was collection of macrophages around the blood vessels in the sub-epithelial layer, the cytoplasm of these macrophages contained stippled cytoplasmic inclusions. The surrounding connective tissue showed thin collagen fibers with sharp delineation between the epithelial and connective tissue layers indicating poor quality of collagen. There was no histological difference between the hemizygous male and the heterozygous female. The present study indicates heterozygous expression of Lesch-Nyhan Syndrome at both the clinical and the ultrastructural levels in favour of extreme lyonization or X-chromosome deletion in the affected female. Our findings also indicate that ultrastructural studies could be sensitive indicators of abnormal uric acid metabolism. Further studies are needed to compare the phenotypic expression of hemizygotes and heterozygotes with Lesch-Nyhan Syndrome at both the clinical and ultrastructural levels.