Had Sir Archibald Garrod discovered (1902) not the relatively benign alkaptonuria but the demonic X-linked uric aciduria (Lesch-Nyhan syndrome), he might have christened inborn disorders of metabolism "terrors" rather than "errors." No more terrifying sight can be imagined than that of a mentally retarded choreoathetotic, spastic, selfmutilated child with bitten-off digits and lips. First described in 1964, and since reported in about 150 cases, the Lesch-Nyhan syndrome still remains a therapeutic challenge, despite its known mode of transmission and its well-defined underlying enzymatic defect. Perpetuated as a sexlinked recessive trait, and characterized by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which results in excessive purine synthesis, the disease leads to early death before the age of puberty. Treatment with adenine and folic acid has failed to cure or improve the severe neurologic symptoms.
In the absence of cure or palliation, the alternative to therapeutic inaction is early termination of pregnancy, if
Inborn Terror of Metabolism. JAMA. 1970;214(12):2186-2187. doi:10.1001/jama.1970.03180120058012