A CASE OF LESCH NYHAN SYNDROME WITH DELAYED ONSET OF SELF MUTILATION: A search for abnormal biochemical, immunological and cell growth characteristics in fibroblasts and neurotransmitters in urine: 194

Surjit Sing, Ingrid Willers, Kurt Ullrich, H Gustmann
1985 Pediatric Research  
A 4-yr old Arab gir1,referred for investigation of hypouricaemia and hypouricosuria discovered during studies for Coombes positive haemolytic anaemia,was found to excrete inosine, guanosine,deoxyinosine and deoxyguanosine in place of uric acid. The patient and a 10-month old brother were homozygous for purine nucleoside phosphorylase (PNP) deficiency. Three of the other four surviving siblings were heterozygotes,as were the parents who were first cousins. Another sibling had died of
more » ... The baby showed head-lag, the girl spastic diplegia. As in our previous case,severe red cell GTP depletionassociated with raised dGTP levels and grossly increased NAD levels, were noted. Red cell PP-ribose-P levels and lysate APRT activity were likewise increased. The clinical findings also accord with previous reports. In addition to immunodeficiency, anaemia and neurological complications (ataxia, spastic tetrasparesis) have been reported in 30-408 of cases. The results suggest that patients with severe PNP deficiency may suffer the consequences of two enzyme defectsimmunodeficiency due to an inability to metabolise toxic deoxynucleosides plus the neurological complications of hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency because of a resultant lack of substrates for the latter. Red cell GTP depletion appears to be a consistent finding in inherited disorders associated with neurodevelopmental retardation.
doi:10.1203/00006450-198507000-00214 fatcat:orx4cwyrirbojotyq2eeha5eri