title: Treatment of mitochondrial encephalomyopathies with a xanthine oxidase inhibitor.
abstract: Five females with mitochondrial encephalomyopathies were treated for 3 to 7 years with a xanthine oxidase inhibitor (allopurinol, oral route, 20 mg/kg/day, in 2 or 3 doses daily). Clinical course was monitored in all patients. In addition, various metabolic variables, namely blood lactic acid, blood adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate were monitored, as well as energy charge. Data obtained were compared with data for an age-matched control group of 10 healthy children. Four of the five patients manifested clinical improvement, and the remaining patient exhibited slower disease progression. Three of the four patients who exhibited clinical improvement also had normalization of blood lactic acid level. All five patients had an increase in blood adenosine triphosphate levels and a decline in blood adenosine monophosphate; four of the five manifested a decline in blood adenosine diphosphate and increased energy charge. Mean blood adenosine triphosphate was significantly increased with respect to pretreatment levels and with respect to the control group; mean energy charge displayed an increase, though this was not statistically significant. In one patient, reduction of the allopurinol dose to 10 mg/kg/day was followed by a decline in both blood adenosine triphosphate level and energy charge, and by clinical worsening. In conclusion, the xanthine oxidase inhibitor allopurinol appears to have had beneficial effects in these patients in terms of both energy metabolism and clinical course.
authors.affiliation: Departamento de Pediatría, Servicio de Neuropediatría, Hospital Clínico Universitario, Santiago de Compostela, Spain. pdcastro@usc.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Castro-Gago
authors.forename: Manuel Oscar
authors.initials: MO
authors.lastname: Blanco-Barca
authors.forename: María Inés
authors.initials: MI
authors.lastname: Novo-Rodríguez
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Lado
authors.forename: Félix
authors.initials: F
authors.lastname: Camiña
authors.forename: Jesús
authors.initials: J
authors.lastname: Eirís-Puñal
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez-Segade
mesh_terms: D000227:Adenine Nucleotides / Q000097:blood; D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood; D017237:Mitochondrial Encephalomyopathies / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D000227:Adenine Nucleotides; D019344:Lactic Acid; D000493:Allopurinol; D014969:Xanthine Oxidase