Among the defects of the amino acid transport in the renal tubule include cystinuria and Crohn Hatnup which are discussed elsewhere. Disorders of the metabolism of amino acids and organic acids include Branched-chain amino acids disorders Methioninstoffwechselstörungen phenylketonuria Tyrosinstoffwechselstörungen urea cycle disorders addition, there are a number of other disorders of the metabolism of amino acid, and of organic acids, including those that beta and gamma amino acids, gamma-glutamyl cycle, glycine, histidine, lysine, proline and hydroxyproline contained and other other amino acid disorders. Beta-amino acid and gamma-amino acid disorders disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks Hyper-?-Alaninemia (237400) ?-alanine-?-Ketoglutarataminotransferase Not determined biochemical profile: Elevated ?-alanine, taurine, ?-amino butyric acid (GABA) and ?-aminoisobutyric acid in the urine Clinical features: seizures, drowsiness, death treatment: Pyridoxine methylmalonate / Malonatsemialdehyd- Dehy drug nose deficiency with 3-amino and 3-Hydroxie-aciduria (236795) methylmalonate / Malonatsemialdehyd- dehydrogenase ALDH6A1 (14q24.3) * biochemical profile: Elevated hydroxyisobutyrate 3-3-aminoisobutyric acid, 3-hydroxypropionate ?-alanine and 2-ethyl -3-hydroxypropionate in urine Clinical features: No light up treatment: Undetermined Methylmalonischer Semialdehyddehydrogenase- deficiency with mild methylmalonic methylmalonic semialdehyde (s. also branched-chain amino acid metabolism, supra) ALDH6A1 (14q24.1) Biochemistry profile: Moderately increased urinary methylmalonate Clinical characteristics: developmental delay, seizures treatment: There is no effective therapy. Hyper-?-aminoisobutyric acid aciduria (210100) D (R) -3-amino isobutyric acid: pyruvate aminotransferase Not determined biochemical profile: Elevated ?-aminoisobutyric acid Clinical features: benign treatment: Not required Pyridoxine dependency with seizures (266100) Not determined Specific gene not determined (5q31.2-q31.3) Biochemistry profile: Elevated glutamate in the cerebrospinal fluid Clinical features: seizures refractory to conventional anti-convulsants, high-pitched crying, hypothermia, tremors, dystonia, hepatomegaly, hypotension, dyspraxia, developmental delay treatment: Pyridoxine GABA transaminase deficiency (137150) of 4-aminobutyric acid ?-ketoglutarate aminotransferase ABAT (16p13.3) * Biochemical profile: Elevated GAB and ?-alanine in blood and cerebrospinal fluid, increased carnosine Clinical features: accelerated linear growth, seizures, cerebellar hypoplasia , psychomotor retardation, leukodystrophy, suppressed discharge patterns in the EEG treatment: No treatment options 4-hydroxybutyrate aciduria (271980) succinic semialdehyde ALDH5A1 (6p22) * Biochemical profile: Increased 4-hydroxybutyrate and glycine in urine Clinical features: psychomotor retardation, speech delay, hypotonia treatment: vigabatrin Carnosinämie, Homocarnosinosis or both (236130, 212200) carnosinase specific gene is not determined (18q21.3) Biochemical profile: In the Carnosinämie phenotype despite Carnosinurie meat ree diet, increased anserine in urine after ingestion of food containing imidazole dipeptides nunauffälliges blood when homocarnosinosis phenotype increased homocarnosine in the cerebrospinal fluid, normal carnosine in serum Clinical features: usually benign; reported symptoms probably due to bias treatment: Not required * The gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Gamma-glutamyl cycle disorders disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks ?-Glutamylzysteinsynthetase deficiency (230450) ?-Glutamylzysteinsynthetase GGLC (6p12) * Biochemical Profile: aminoaciduria, glutathione deficiency Clinical characteristics : hemolysis, spinocerebellar degeneration, peripheral neuropathy, myopathy treatment: No clear treatment, avoid drugs that cause haemolytic crisis in G6PD deficiency Pyroglutamische aciduria (5-Oxoprolinurie; 266130, 231900) glutathione GSS (20q11.2) * Biochemical Profile of 5-oxoproline increases in urine, blood and cerebrospinal fluid; increased ?-glutamyl cysteine, reduced glutathione levels Clinical features: hemolysis, ataxia, seizures, mental retardation, spasticity, metabolic acidosis In the mild form no evidence of neurological damage Treatment: sodium bicarbonate or citrate, vitamins E and C, avoid drugs that in G6PD deficiency can cause haemolytic crisis ?-glutamyl-deficiency (Glutathionurie; 231950) ?-glutamyl-specific gene is not determined (22q11,1-q11,2) Biochemistry profile: increased glutathione in urine and blood Clinical features: Mental retardation treatment No specific treatment. 5-oxoprolinase deficiency (260005) 5-oxoprolinase Not determined biochemical profile: 5-oxoproline in urine increased Clinical features: Probably benign treatment not required * The gene was identified and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Glycine metabolic disorders disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks Nonketotische hyperglycinemia (605,899) glycine cleavage enzyme system biochemical profile: Glycine increases in blood and CSF Clinical Features: The neonatal form – hypotonia , seizures, myoclonus, apnea, death In infantile and episodic forms: seizures, mental retardation, episodic delirium, chorea, vertical gaze palsy In the late onset form: progressive spastic diplegia, optic atrophy But no cognitive impairment or seizures Treatment: No effective treatment; some patients benefit temporarily from sodium benzoate and dextromethorphan P protein GLDC (9p22) * H protein GCSH (16q23) * T-protein ATM (3p21) * L protein Not determined * The gene was identified and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Histidine metabolism disorders disease (OMIM number) Defective proteins or enzymes defective gene or genes (chromosomal location) Comments Histidinaemia (235800) Classic: L-histidine ammonia lyase (liver and skin) Variant: L-histidine ammonia lyase (only liver) HAL (12q22-q23) * Biochemical profile of histidine in the blood increases Clinical features: Common benign; neurological manifestations in some patients treatment: Low protein diet only in symptomatic patients: a controlled intake of histidine urocanic acid aciduria (276880) urocanase Not determined Biochemical Profile of urocanic acid in the urine increases Clinical features: Probably benign treatment: Not required * The gene was identified and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Lysine-metabolic disorders disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks Hyperlysinämie (238700) lysine: ?-Ketoglutaratreduktase AASS (7q31.3) * Biochemical Profile: Hyperlysinemie Clinical features: muscle weakness, seizures, light anemia, mental retardation, joint and muscle instability, ectopia lentis; sometimes benign treatment: Limited lysine use 2-Ketoadipische acidemia (245130) 2-Ketoadipische dehydrogenase Not determined biochemical profile: 2-Ketoadipate, 2-aminoadipate and 2-Hydroxyadipat in urine increased Clinical features: benign treatment: Not required Glutarazidämie type I ( 231670) glutaryl-CoA dehydrogenase (19q13.2) * Biochemical profile of glutaric acid and 2-hydroxyglutaric acid in urine increased Clinical features: dystonia, dyskinesia, degeneration of the caudate and putamen, frontotemporal atrophy, arachnoid cysts treatment: Aggressive treatmen development of the underlying disease, carnitine, reduction of protein, lysine and tryptophan may be helpful Saccharopinurie (268,700) ?-Aminoadipische Semialdehydglutamatreduktase AASS (7q31.3) * Biochemical Profile: lysine, citrulline, histidine and saccharopine in urine increased Clinical features: mental retardation, spastic diplegia, short stature, EEG abnormality treatment: No clear treatment * the gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Proline and hydroxyproline metabolic disorders disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks hyperprolinemia, type I (239500) Prolinoxidase (Prolindehydrogenase) PRODH (22q11.2) * Biochemical Profile: Increased proline in the blood , hydroxyproline and glycine in urine Clinical features: benign typically; hereditary nephritis, deafness treatment: Not required hyperprolinemia, type II (239510) ?1-pyrroline-5-carboxylate dehydrogenase P5CDH (1p36) * Biochemical Profile: Increased proline and pyrroline-5-carboxylate (P5C) in the blood; increased P5C, ?1, pyrroline 5-carboxylate, proline, hydroxyproline and glycine in urine Clinical features: During childhood, seizures, mental retardation in adulthood, benign treatment: Not required ?1-pyrroline-5-carboxylate synthetase deficiency (138250) ?1-pyrroline-5-Carboxylatsynthetase PYCS (10q24.3) * Biochemical profile: Decreased proline, citrulline, arginine and ornithine in blood Clinical features: hyperammonemia, cataracts, mental retardation, joint instability treatment: No fasting Hyperhydroxyprolinämie (237000) 4-Hydroxyprolinoxidase Not certainly Biochemical profile: Hydroxyprolinämie Clinical features: Disease association not proven treatment: Not required prolidase deficiency (170100) Prolidase PEPD (19q12-q13.11) * biochemical profile: amino acid profile normal in hydrolyzed urine, but excessive proline and hydroxyproline in acid hydrolysed urine Clinical Features : ulcers of the skin, frequent infections, facial dysmorphism, immunodeficiency, mental retardation treatment: proline-Supplement, Mn + + and ascorbic acid, essential amino acids, blood transfusion (packed red blood cells), topical proline and Glyzinsalbe * the gene was identified And the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Various disorders of the metabolism of amino acids and organic acids disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks Sarkosinämie (268900) sarcosine dehydrogenase specific gene not determined (9q34) Biochemical Profile of sarcosine in the blood increases Clinical features: Benign; of mental retardation have been reported treatment: Not required D-glyceric acid-aciduria (220120) D-Glykeratkinase Not determined biochemical profile: D-glyceric acid in urine increased Clinical features: Chronic acidosis, hypotension, seizures, mental retardation treatment: bicarbonate or citrate at acidosis Hartnup disorder system B (0) neutral amino acid transporter SLC6A19 (5p15) * Biochemical profile: neutral aminoaciduria Clinical features: Atrophic glossitis, photodermatitis, intermittent ataxia, hypertension, seizures, psychosis treatment: Nicotinamides Zysteinurie Renal dibasic amino acid transporter – Biochemical Profile of cystine, lysine, arginine and ornithine in the urine increases Clinical features: nephrolithiasis, increased risk restricted brain function treatment: conservation of fluid intake, bicarbonate or citrate, penicillamine or Mercaptopropionylglyzin type I (220100) Heavy subunit SLC3A1 (2p16.3) * type II and III (600,918) Light subunit SLC7A9 (19q13.1) * Iminoglyzinurie (242600) Renal transport of proline, hydroxyproline and glycine Not determined Biochemical Profile: proline, hydroxyproline and glycine increased in the urine, but unobtrusive glycine in blood Clinical features: Probably benign treatment: Not required Guanidinoacetatmethyltransferase deficiency (601240) Guanidinoacetatmethyltransferase GAMT (19p13 .3) * Biochemical profile: Increased guanidinoacetate, humiliated creatine and creatine phosphate Clinical features: developmental delay, hypotension, extrapyramidal movements, seizures, autistic behaviors Behan dlung: calcium supplementation p.o. or iv Cystinosis See Table Lysosomal transport defect * The gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (s. The OMIM database on http://www.ncbi.nlm.nih.gov/omim).

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