The physiopathology of neurological signs in hypoxanthine-guanine phosphoribosyltransferase deficiency
Objective. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is characterized by an increase in renal uric acid excretion, usually with hyperuricemia and may be associated with more or less important neurological symptoms. Based on a series of 20 patients from 16 Spanish families we propose that HPRT deficiency could be clinically classified in four different groups. In the more severe form (classic Lesch-Nyhan syndrome) HPRT deficiency is characterized by choreoathetosis, spasticity, mental retardation and compulsive self-mutilation behavior. The pathophysiology of the neurological symptoms remains unclear and there is no effective therapy. This review is intended to provide a research strategy for a better knowledge of the neurological pathophysiology of HPRT deficiency. Development. We have analyzed the knowledge on the neurological symptoms of HPRT deficiency. This knowledge comes from histopathological studies of the brains from Lesch-Nyhan patients, chemical studies of the cerebrospinal fluid, experimental animal models (pharmacologic and lesioning and genetic approaches), and human in vivo studies with positron-emission tomography. Conclusions. The observed findings suggest that the neurological symptoms of Lesch-Nyhan syndrome could be related with the neonatal neuronal and/or dopaminergic terminations damage. This damage could be due to lost or reorganization of dopaminergic system, and is associated with a reduced dopamine levels and with hypersensitivity of the D1 subclass dopamine receptors
Desarrollo El conocimiento de la afectación neurológica asociado a la deficiencia de HPRT se ha generado mediante estudios anatomopatológicos en cerebros de pacientes con síndrome de Lesch-Nyhan, estudios de los constituyentes bioquímicos del líquido cefalorraquídeo, modelos animales experimentales (farmacológicos lesionales y genéticos) y estudios realizados en humanos in vivo gracias a la tomografía de emisión de positrones.
Conclusiones Los datos obtenidos indican que las alteraciones neurológicas del síndrome de Lesch-Nyhan podrían estar relacionadas con el daño neuronal neonatal y/o de las terminaciones dopaminérgicas. Este daño podría consistir en una pérdida y/o reorganización del sistema dopaminérgico y se acompaña de una disminución de los niveles de dopamina y de una hipersensibilidad a los receptores de dopamina subclase D1
