In addition to purine salvage disease, purine metabolism 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 purine salvage disease, purine metabolism disorders (see also Table) including purine catabolism disorders purine nucleotide synthesis disorders See also approach in a patient with suspected congenital metabolic disorder and investigation for suspected inherited metabolic disorders. Disorders of purine metabolism disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks calcium pyrophosphate arthropathy (chondrocalcinosis, 2 .; 118600) Increased Nukleosidtriphosphatpyrophosphohydrolase ANKH (5p15.2-P14.1) * Biochemical Profile : 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 form of variable shape hypoxanthine guanine phosphoribosyl HPRT (Xq26-q27.2) * Biochemical Profile: hyperuricemia, hyperuricosuria Clinical Characteristics: Orange sand-like crystals in diapers, growth disorders, uric acid nephropathy and joint diseases, delay in movement, hypotension, self-injury, spasticity, hyperreflexia, extrapyramidal signs 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 Sy nthetase (311,850) phosphoribosylpyrophosphate PRPS1 (Xq22-q24) * Biochemical Profile: 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, sulfinpyrazone phosphoribosylpyrophosphate deficiency (311850) phosphoribosylpyrophosphate PRPS1 (Xq22-q24) PRPS2 (Xp22,3-p22,2) Biochemical profile: increased orotate in urine, Hypouricämie Clinical features: En twicklungsstörungen, seizures with hypsarrhythmia, megaloblastic bone marrow treatment: ACTH Hereditary Xanthinuria biochemical 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 features: urolithiasis, nephropathy, round yellow-brown urine crystals treatment: High fluid intake, low purine diet, avoiding dietary bases, kidney transplant ion 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, experimental Increased adenosine deaminase gene therapy (102730) adenosine deaminase ADA biochemical profile: Slight hyperuricemia Clinical features: anemia with Anisopoikilocytosis and Stomatocytosis treatment: deoxycoformycin 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). Lesch-Nyhan syndrome This rare X-linked recessive disease is caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HPRT). The extent of the defect (and hence the symptoms) varies depending on the specific mutations. A HPRT deficiency leads to hypoxanthine and guanine can not be provided on the “salvage pathway”. Instead, the purines are converted to uric acid. In addition, the reduction of the Inositolmonophosphats and Guanosylmonophosphats leads to an increased conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-Phosphoribosylamin, which additionally enhances the uric acid overproduction. Hyperuricemia makes them susceptible to gout and its complications. Patients have a number of cognitive disorders and behavioral changes. The etiology is unclear, she does not seem to be associated with uric acid. The disease usually manifests between 3 and 12 months with orange colored, sandy failure in the urine (xanthine). It proceeds with CNS involvement with mental retardation, spastic cerebral seizures, involuntary movements and selbstverstümmelndem behavior (especially biting). Later, a chronic hyperuricemia can symptoms of gout (z. B. urolithiasis, nephropathy, gouty arthritis, tophi) cause. The diagnosis of Lesch-Nyhan syndrome is suspected in a combination of dystonia, retardation and self-mutilation. The serum uric acid are increased, but to confirm HPRT enzyme assay is initiated. For CNS disorders, no treatment is known, it is treated only symptomatically. For this, a number of medications available. The self-mutilation can sometimes make a physical fixation, tooth extractions and drug treatment required. The hyperuricemia is a purinarmen diet (z. B. avoid organ meats, beans, sardines) and allopurinol, a xanthine oxidase inhibitor treated (the last enzyme in the purine metabolism). Allopurinol prevents the conversion of the accumulated hypoxanthine to uric acid. Because hypoxanthine is very soluble, it is then excreted. Adenine deficiency In this rare autosomal recessive disease can not be provided from the adenine metabolic pathway for the synthesis of purine. The accumulated adenine is oxidized to 2,8-Dihyroxyadenin which precipitates in the urinary tract and causes similar problems as with a uric acid nephropathy (z. B. renal colic, frequent infections and if diagnosed too late, renal failure). The onset of the disease can occur in any age. T he normal uric acid levels. The diagnosis of adenine phosphoribosyltransferase deficiency is provided due to increased 2.8-Dihydroxyadenin-, 8-Hydroxyadenin- and Adeninspiegel in urine and confirmed by enzyme assay. T he treatment of adenine phosphoribosyltransferase deficiency consists in a restriction of oral Purinzufuhr, high fluid intake and avoidance of Urinalkalisierung. A kidney transplant may be necessary in renal failure. Allopurinol can prevent the oxidation of adenine.

Health Life Media Team

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