Enzyme Replacement in the Lesch-Nyhan Syndrome with Long-Term Erythrocyte Transfusions
The pathogenesis of the neuro-behavioral abnormalities associated with the Lesch-Nyhan syndrome remains obscure despite recent reports of neurotransmitter abnormalities in these patients1. Many attempts to correct the characteristic manifestations of spasticity, mental retardation, choreoathetosis, and compulsive self-mutilation have been reported but none have reported sustained clinical efficacy. Many pathogenic mechanisms have been proposed over the past two decades to explain the relationship between the known aberration in purine metabolism and the observed neurologic dysfunction. One of these proposed mechanisms is that the absence of the purine salvage pathway in the central nervous system (CNS) results in (1) the accumulation of oxypurines in the spinal fluid which then may act as toxic endogenous mediators2 and (2) the depletion of guanine and adenine nucleotides that are important to normal CNS function3–5. Supplementation of purine intermediates with dietary adenine, guanosine, inosine, and GMP have not altered the clinical course of the disease.
KeywordsEnzyme Replacement Therapy Purine Metabolism Transfusion Therapy Characteristic Manifestation Adenine Phosphoribosyltransferase
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