Chemical Pathology

Question 1

Outline the clinical features of Lesch-Nyhan Syndrome

Answer 1

1) At Birth- Normal
2) At 6 months- Developmental delay, Hyperuricaemia
3) At 1 year- Choreiform movements
4) Spasticity and Mental Retardation
5) Self Mutilation present in 85% (eg biting lips very hard)

Question 2

Describe the biochemical basis of Lesch-Nyhan syndrome

Answer 2

1) Absolute deficiency of HPRT(Hypoxanthine phosphoribosyltransferase)
2) So less production of IMP and GMP via the salvage pathway.
3) Less conversion of guanine to GMP so accumulation of PPRP.
4) IMP and GMP are inhibitory on PAT, and PPRP is stimulators on PAT.
5) This massively increases production of IMP from the de novo pathway, which gets shunted through the catabolic pathway.
6) Leading to mass production and accumulation of urate.