Adenine and Folic Acid in the Lesch-Nyhan Syndrome
| Autor: | Paul J. Benke, Carolyn R. Aradine, Norma Herrick, Ronald H. Laessig, Lizabeth Smitten, George J Wolcott |
|---|---|
| Rok vydání: | 1973 |
| Předmět: |
Male
Purine medicine.medical_specialty Erythrocytes Lesch-Nyhan Syndrome Monosodium glutamate Hamster In Vitro Techniques Central nervous system disease chemistry.chemical_compound Folic Acid Glutamates Central Nervous System Diseases In vivo Cricetinae Internal medicine Diseases in Twins medicine Animals Humans Carbon Radioisotopes Pentosyltransferases business.industry Adenine Infant Newborn Glutamate receptor medicine.disease Stimulation Chemical Jejunum Endocrinology chemistry Biochemistry Depression Chemical Pediatrics Perinatology and Child Health Uric acid Lesch–Nyhan syndrome business |
| Zdroj: | Pediatric Research. 7:729-738 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-197309000-00001 |
| Popis: | Extract: Therapy of identical twin males with the enzyme defect of the Lesch-Nyhan (L-N) syndrome was instituted at 12 hr of age with adenine, 10 mg/kg/24 hr, administered to one twin and folic acid, 15 mg/24 hr, to both. At 4 years of age both twins demonstrate delayed neurologic development and spasticity but are less severely affected than most other patients with this disorder. Administered in subsequent studies to two maternal cousins of the twins who had clinical features of the L-N syndrome and absence of erythrocyte hypoxanthine-guanine phosphoribosyltransferase activity were adenine, 10 mg/kg/24 hr, adenine, 40 mg/kg/24 hr, folic acid, and mono-sodium glutamate. Low dose adenine had a slight suppressive effect on glycine-l-14C incorporation into uric acid; high dose adenine had a strong suppressive effect in the second patient. We conclude that the adenine dose chosen for therapy was too low. 2,8-Dihydroxyadenine, a toxic breakdown product of adenine, was detected in the urine at both adenine dose levels. Folic acid and monosodium glutamate in these patients further stimulate accelerated glycine-l-14C incorporation into uric acid. In vitro transport studies, performed with inverted hamster jejunal preparations, suggest that adenine is largely converted to adenine monophosphate when exposed to the mucosal surface. This may limit the passage of orally administered adenine to the central nervous system in patients. Adenine and purine precursors affect the biochemical pathology of the L-N syndrome, in vivo and in vitro, but therapeutic use of adenine, 10 mg/kg/24 hr, and folic acid started on the 1st day of life did not prevent central nervous system dysfunction. Speculation: Variation in clinical presentation occurs in the Lesch-Nyhan syndrome. Although small therapeutic benefit may be ascribed to folic acid therapy in our patients, this is not established with certainty. A different approach may be required to prevent central nervous system disease in patients treated from birth. |
| Databáze: | OpenAIRE |
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