See also approach in a patient with suspected congenital metabolic disorder
Purines are newly synthesized or recycled by ( “salvage pathway”) on a special pathway from the normal catabolism be “safe”. The catabolism of purines produced intermediate components of the citric acid cycle. Disorders of purine and pyrimidine (see table). See also approach in a patient suspected of having an inborn error of metabolism disorders of pyrimidine metabolism disorder (OMIM number) Defective proteins or enzymes defective gene or genes (chromosomal location) Comments Hereditary Orotazidurie Biochemical Profile: Increased orotate in urine Clinical features: megaloblastic, recurrent infections, cellular immune deficiencies, developmental disorders treatment: uridine, uridyl and cytidylic acid Type I (258,900) UMP synthase (orotidine decarboxylase and 5’Pyrophosphorylase-) UMPS (3q13) * Type II (258920) orotidine-5′-decarboxylase – dihydropyrimidine dehydrogenase deficiency (274,270) Congenital error Pharmacogenetic form DPYD dihydropyrimidine dehydrogenase ( 1P22) * biochemical profile: Elevated uracil, thymine and 5-hydroxymethyluracil in urine Clinical features: When congenital disorder of growth and developmental delay, convulsions, spasticity, micro zephalie When pharmacogenomics form of side effects of 5-flurouracil, including myelosuppression, neurotoxicity, gastrointestinal symptoms and skin lesions, death Treatment: No specific treatment other than discontinuing the offending drug Dihydropyrimidinurie (222748) Dihydropyrimidinase DPYS (8q22) * Biochemical Profile: Increased dihydrouracil and dihydrothymine in urine Clinical features: variable; Feeding problems, seizures, lethargy, drowsiness, metabolic acidosis Sometimes benign treatment: Not determined ?-ureido-propionase deficiency (210100) ?-ureido-propionase (?Alanin synthase) UPB1 (22q11,2) Biochemistry profile: Elevated Ureidopropionat and Ureidobutyrat in urine Clinical features: microcephaly, developmental delay, dystonia, scoliosis treatment: Not set pyrimidine 5’Nucleotidase deficiency (266120) 5’Monophosphate hydrolase NT5C3 (7p15-p14) * Biochemical profile: No specific profile Clinical features: anemia, basophilic Punktie tion Treatment: Supportive care activation induced Cytidindesaminase- deficiency (Hyper-IgM syndrome type II; 605257) activation-induced cytidine deaminase AICDA (12p13) * Biochemical Profile: High IgM, low to nonexistent IgG and IgA Clinical features: Recurring bacterial infections, poor Ig class switching treatment: infection control * The gene was identified, and the molecular basis is elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Uridinmonophosphatsynthase deficiency (hereditary Oratazidurie) The enzyme catalyzes the uridine monophosphate Orotatphosphoribosyltransferase- and orotidine-5′-Monophosphatdecarboxylasereaktionen. A deficiency, the orotic acid is accumulated and causes clinical manifestations such as megaloblastic anemia, Orotkristallurie and nephropathy, cardiac malformations, strabismus and recurrent infections. The diagnosis of uridine monophosphate synthase deficiency is provided by an enzyme assay in various tissues. (See also check on suspicion of inherited metabolic disorders.) The treatment of uridine monophosphate synthase deficiency by oral supplementation with uridine.