HGPRTdeficient

HGPRT deficiency denotes reduced or absent activity of the enzyme hypoxanthine-guanine phosphoribosyltransferase, encoded by the HPRT1 gene on the X chromosome. The enzyme is part of the purine salvage pathway, recycling hypoxanthine and guanine to inosine monophosphate and guanine monophosphate.

Inheritance is X-linked recessive. Mutations in HPRT1 lead to complete deficiency (Lesch-Nyhan syndrome) or partial deficiency (Kelley-Seegmiller syndrome). Complete deficiency results in severe neurodevelopmental impairment and self-injurious behavior; partial deficiency yields milder hyperuricemia and motor symptoms.

The lack of HGPRT activity causes increased de novo purine synthesis and uric acid production, with hyperuricemia and urate nephrolithiasis. Neurologic features include dystonia, dystonic posturing, chorea, dysarthria, and cognitive impairment; self-injurious behaviors are characteristic in classic Lesch-Nyhan syndrome. Age of onset is infancy to early childhood.

Confirmation by measuring HGPRT enzymatic activity in leukocytes or cultured cells, or by identifying pathogenic mutations in HPRT1. Plasma and urine urate elevated. Additional testing may include renal ultrasound in stone risk and developmental assessment.

Management is supportive and multidisciplinary. No cure exists. Allopurinol reduces uric acid production; hydration and kidney stone prevention are important. Movement disorders are managed with physical and occupational therapy; behavioral strategies and protective devices help with self-injury; dental guards may be used.

Lesch-Nyhan is rare. Estimates suggest occurrence in about 1 in 380,000 male births for the classic form; partial deficiency is less well defined. Prognosis depends on severity and complications; survival can extend into adulthood with multidisciplinary care, though neurologic impairment typically persists.