LESCH-NYHAN SYNDROME – late diagnosis of rare disease: clinical case

Abstract

Background. Lesch-Nyhan syndrome is inherent X-linked recessive genetic disorder with decreased activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). The disease is characterized by presence of the classical triad: hyperuricemia, neurological and behavioral changes. In the article we present a clinical case of Lesch-Nyhan syndrome first diagnosed only at 16 years old despite the fact that the clinical clues were already found at the patient`s early age. Case presentation. An 18-year-old Caucasian man was admitted to the rheumatology department because of gouty arthritis. In neonatal period he was diagnosed with mild intrauterine growth restriction by hypoplastic type. Uric acid crystals were found in our patient`s urine at 6-month-old. In the first year of life, delayed motor development was noted together with permanent neurological changes which were referred to rickets. During school years, severe dysgraphia, dyslexia, dysarthria, logoneurosis warranted observation by a speech therapist. At his 12 he had been diagnosed with nephrocalcinosis, at 14 – with chronic kidney disease and symptomatic arterial hypertension. The family history was remarkable for gout in grandmother and great-grandmother, chronic pyelonephritis – in mother, urate nephropathy – in both brothers. In physical examination hyperemia and edema of the left first metatarsophalangeal joint, left ankle defiguration, funnel chest, gynecomastia, tophi on the ears were noted. On examination, some neurological disorders and mild cognitive impairment were found. In investigations hyperuricemia, arthritis of the first metatarsophalangeal joint, diffuse changes in the renal parenchyma with impaired renal excretory function were detected. Despite the clues in patient`s anamnesis, objective examination and additional investigation, as well as the presence of a family anamnesis suggesting the hereditary nature of hyperuricemia, the diagnosis of HGPRT deficiency was not made until the age of 16 years. Conclusion. The presence of Lesch-Nyhan syndrome can be assumed with the progression of muscle tone impairment and movement disorders in a child after the first six months of life in combination with high plasma uric acid concentration and its increased urinary excretion. Difficulties in the syndrome diagnosis are associated not only with a rare occurrence, but with a slight or moderate degree of central nervous system impairment that is often related by doctors to rickets or delivery trauma, as well as low accessibility of molecular genetic testing.