Besides purine catabolism disorders purine metabolic disorders include (see also table)
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. Purine and pyrimidine are newly synthesized or recycled by being “recovered” on a specific pathway ( “salvage pathway”) from the normal catabolism. The final product of the complete catabolism of purines is the uric acid. Besides purine catabolism disorders purine metabolic disorders include (see also table) purine nucleotide synthesis disorders purine salvage diseases 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 alkalis, kidney Trans Planta tion 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 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). Myoadenylatdesaminase deficiency (or muscle Adenosinmonophosphatdesaminase deficiency) These enzymes convert AMP to inosine and ammonia. A deficiency may be asymptomatic or cause during exercise myalgias or cramps. The expression appears to be variable, despite the high number of mutant alleles (10-14%) because the frequency of Muskelphänotyps in patients who are homozygous for the mutant allele is low. If symptomatic patients engage in any physical, ammonia or inosine monophosphate not accumulate as nichtaffizierten people. In this way the disease is diagnosed. The treatment of a Myoadenylatedeaminasemangels is, if required from a movement modulation. Adenosine deaminase deficiency Adenosine deaminase converts adenosine and deoxyadenosine to inosine and deoxyinosine in which are further broken down and excreted. An enzyme deficiency (1 of> 60 known mutations) leads to the accumulation of adenosine, which then by cellular kinases in its ribonucleotides and deoxyribonucleotides (dATP) is converted. The increase of dATP leads to inhibition of ribonucleotide reductase and reducing production of other deoxyribonucleotides. As a result, DNA replication is impaired. Especially immune cells are susceptible to this disorder. The adenosine deaminase deficiency leads to a severe form of combined immunodeficiency disease. The diagnosis of Adenosindeaminasemangels is provided by a low erythrocyte and Leukozytenenzymaktivität. A bone marrow or stem cell transplantation and enzyme replacement therapy are necessary for the treatment of adenosine deaminase deficiency. A somatic cell therapy is being tested at the moment. Purine nucleoside phosphorylase deficiency This rare autosomal recessive disorder characterized by immune deficiency with a strong T-cell dysfunction and neurological symptoms. The manifestations are lymphopenia, Thymusstörung repeated infections and a hypouricemia. Many patients have a developmental delay, ataxia or spasticity. A diagnosis of a purine nucleoside phosphorylase deficiency by low enzyme activity of red blood cells. Treatment consists of a bone marrow or stem cell transplantation. Xanthinoxidasemangel xanthine oxidase, the enzyme that catalyzes the production of uric acid from xanthine and hypoxanthine. A deficiency causes the accumulation of xanthine, which precipitates in the urine, causing symptomatic stones with hematuria, Harnwegskoliken and urinary tract infections. The diagnosis of xanthine oxidase deficiency is detected due to a low uric acid, a high excretion in the urine and high serum levels of hypoxanthine and xanthine. Enzyme determination one needs a liver or intestinal Mucosabiopsie, it is rarely indicated. The treatment of a xanthine oxidase deficiency is in a high fluid intake, in order to minimize scale formation, and in some patients in the administration of allopurinol.