In addition to disorders of purine nucleotide synthesis, purine metabolic disorders (see also Table, including
Purines are key components of cellular energy system (eg. B. ATP, NAD), the signal paths (z. B. GTP, cAMP, cGMP), and the pyrimidines of the RNA and DNA form. Purines are newly synthesized or recycled by ( “salvage pathway”) on a special pathway from the normal catabolism be “safe”. The final product of the complete catabolism of purines is the uric acid. In addition to disorders of purine nucleotide synthesis, purine metabolism disorders (see also table, including purine catabolism disorders purine salvage diseases See also approach in a patient with suspected congenital metabolic disorder and investigation for suspected inherited metabolic disorders. Disorders purine metabolism disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks calcium pyrophosphate arthropathy (chondrocalcinosis, 2 .; 118600) Increased nucleos idtriphosphatpyrophosphohydrolase ANKH (5p15.2-P14.1) * Biochemical Profile of calcium pyrophosphate dihydrate crystals in the joints Clinical features: Repeated episodes of monoarticular or multiarticular Arthritis Treatment: No clear treatment Lesch-Nyhan syndrome (300322) Classic shape variable form of hypoxanthine, guanine phosphoribosyltransferase HPRT (Xq26-q27.2) * Biochemical profile: hyperuricemia, hyperuricosuria Clinical characteristics: Orange sand-like crystals in diapers, growth disorders, uric acid nephropathy and joint diseases, motion delay, hypotension, self-injurious behavior, spasticity, hyperreflexia, extrapyramida le sign with choreoathetosis, dysarthria, dysphagia, developmental disorders, megaloblastic In the variable form, no self-injury Treatment: Supportive care, protection, allopurinol, benzodiazepine, certain experimental approaches Increased activity of Phosphoribosylpyrophosphatamidotransferase synthetase (311850) phosphoribosylpyrophosphate PRPS1 (Xq22-q24) * Biochemical profile of hyperuricemia Clinical features: Megaloblastisches bone marrow, ataxia, hypotension, hypertension, psychomotor retardation, polyneuropathy, cardiomyopathy, heart failure, uric acid nephropathy and joint diseases, diabetes mellitus, intracerebral calcification treatment: allopurinol, anti-inflammatory drugs, colchicine, probenecid, Sulfi npyrazon phosphoribosylpyrophosphate deficiency (311,850) phosphoribosylpyrophosphate PRPS1 (Xq22-q24) PRPS2 (Xp22,3-p22,2) Biochemistry profile: Elevated orotate in urine, Hypouricämie Clinical characteristics: developmental disorders, seizures with hypsarrhythmia, megaloblastic bone marrow treatment: ACTH Hereditary Xanthinuria Biochemistry profile: xanthinuria, Hypouricämie, Hypouricosurie Clinical features: xanthine stones, nephropathy, myopathy treatment: High fluid intake; purine diet type I (278,300) lactate dehydrogenase XDH (2p23-p22) * Type II (603592) xanthine dehydrogenase and aldehyde oxidase – adenine phosphoribosyltransferase deficiency (102600) adenine phosphoribosyltransferase APRT (16q24.3) * Biochemical Profile: 2,8-dihydroxyadenine in urine Clinical characteristics : urolithiasis, nephropathy, round yellow-brown urine crystals treatment: High fluid intake, low purine diet, avoiding dietary bases, Nierentranspla ntation Type I No enzyme activity type II residual enzyme activity Adenosindesaminasemangel (102700) adenosine deaminase ADA (20q13,11) * Biochemical Profile: Increased adenosine and 2′-deoxyadenosine in the serum Clinical features: growth retardation, skeletal changes, recurrent infections, severe combined immunodeficiency, B- cell lymphoma, anemia, idiopathic thrombocytopenia, hepatosplenomegaly, mesangial sclerosis treatment: Supportive care, enzyme supplementation, bone marrow or stem cell transplantation experiments, lle gene therapy Increased adenosine deaminase (102730) adenosine deaminase ADA biochemical profile: Slight hyperuricemia Clinical features: anemia with Anisopoikilocytosis and Stomatocytosis BehandlungDeoxycoformyzin purine nucleoside phosphorylase deficiency (164050) purine nucleoside phosphorylase NP (14q13.1) * Biochemical Profile: hypouricemia; Hypouricosurie, increased inosine and guanine in the blood; increased inosine, 2’Desoxyinosin- and 2′-Deodyguanosin in urine Clinical features: growth disorder, cellular immune deficiency, recurrent infections, hepatosplenomegaly, cerebral vasculitis, spastic diplegia tetra paresis, ataxia, tremor, hypotension, hypertension, developmental disorders, autoimmune hemolytic anemia, idiopathic thrombocytopenia , lymphoma, lymphosarcoma The treatment consists in a bone marrow or stem cell transplantation. Myoadenylatdesaminase deficiency (Adenosinmonophosphatdesaminase deficiency I, 102770) Myoadenylate deaminase AMPD1 (1p21-p13) * Biochemical Profile: No specific change Clinical features: Neonatal weakness and hypotension; Weakness or cramps after exercise; reduced purine distributions and their low increase in serum ammonia (relative to lactate) Treatment: ribose or xylitol adenylate kinase deficiency (103000) adenylate AK 1 (9q34.1) * Biochemical Profile: No specific change Clinical features: Anemia Treatment: Supportive care adenylosuccinate lyase deficiency (103050) type I (severe form) type II (mild form) Adenylosuccinatlyase ADSL (22Q13.1) * biochemical profile: Elevated Succinyladenosine and Succinylaminoimidazol- Carboxamidribotide in body fluids Clinical features: Autism, severe psychomotor retardation, seizures, delayed growth, muscle Treatment: Supportive care, adenine and ribose * The gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Phosphoribosyl synthetase activity This Super X-linked disease causes an overproduction of purine. Excess purine is broken down and leads to hyperuricemia and gout, neurological and developmental pathologies. T he diagnosis of Phosphoribosylpyrophosphate synthetase Super Activity is set to red blood cells or skin fibroblasts due to enzyme assays. A phosphoribosyl synthetase activity Super-treatment is performed with allopurinol and a purine diet. Adenylosuccinase deficiency This autosomal recessive disorder caused a pronounced mental retardation, autistic behavior and seizures. The diagnosis of Adenylosuccinasemangels is delivered in the cerebrospinal fluid and urine due to an increase of Succinylaminoimidazolcarboxamid riboside and Succinyladenosins. There is no effective treatment for a adenylosuccinate deficiency.