A protein metabolism disorder where excess amino acids are present in the urine Primary aminoaciduria Secondary aminoaciduria Primary aminoaciduria is due to the enzyme defect in the metabolism of aminoacids Eg. Phenylketonuria, Tyrosinemia Secondary aminoaciduria is due to the defect in the amino acid transporter in the kidney and intestine Eg. Cystinuria, Hartnup disease
Major categories Forms Amino acids involvedAcidic aminoacids Acidic aminoaciduria Glutamate, AspartateBasic amino acids and Cystinuria Cystine, lysine,cystine arginine, ornithine Lysinuric protein Lysine, arginine, intolerance ornithine Isolated cystinuria Cystine Lysinuria Lysine
Acidic aminoaciduria involves the transport of glutamate and aspartateIt results from a defect in the high-affinity sodium potassium– dependent glutamate transporterIt is a clinically benign disorderCystine actually is a neutral amino acid that shares a common carrier with the dibasic amino acids lysine, arginine, and ornithine.The transport of all four amino acids is disrupted in cystinuriaThe rarer disorder, lysinuric protein intolerance, results fromdefects in the basolateral transport of dibasic amino acids but notcystine
Hartnup disease involves a neutral amino acid transport system in both thekidney and intestineBlue diaper syndrome involves a kidney-specific tryptophan transporterMethioninuria appears to involve a separate methionine transport system inthe proximal tubuleIminoglycinuria and glycinuria are clinically benign disorders
In micromoles per deciliter (micromol/dL)Alanine Carnosine Hydroxyproline Children: 65 to 190 Children: 34 to 220 Children: not measured Adults: 160 to 690 Adults: 16 to 125 Adults: not measuredAlpha-aminoadipic acid Citrulline Isoleucine Children: 25 to 78 Children: 0 to 13 Children: 3 to 15 Adults: 0 to 165 Adults: 0 to 11 Adults: 4 to 23Arginine Cystine Leucine Children: 10 to 25 Children: 11 to 53 Children: 9 to 23 Adults: 13 to 64 Adults: 28 to 115 Adults: 20 to 77Asparagine Glutamic acid Lysine Children: 15 to 40 Children: 13 to 22 Children: 19 to 140 Adults: 34 to 100 Adults: 27 to 105 Adults: 32 to 290Aspartic acid Glutamine Methionine Children: 10 to 26 Children: 150 to 400 Children: 7 to 20 Adults: 14 to 89 Adults: 300 to 1,040 Adults: 5 to 30
Ornithine Proline Threonine Children: 3 to 16 Children: not Children: 25 to 100 Adults: 5 to 70 measured Adults: 80 to 320 Adults: not measuredPhenylalanine Serine Tyrosine Children: 20 to 61 Children: 93 to 210 Children: 30 to 83 Adults: 36 to 90 Adults: 200 to 695 Adults: 38 to 145Beta-alanine Glycine 1-methylhistidine Children: 0 to 42 Children: 195 to 855 Children: 41 to 300 Adults: 68 to 855 Adults: 0 to 93 Adults: 750 to 2,400Beta-amino-isobutyric acid Histidine 3-methylhistidine Children: 25 to 96 Children: 46 to 725 Children: 42 to 135 Adults: 64 to 320 Adults: 10 to 235 Adults: 500 to 1,500Phosphoserine Taurine Valine Children: 16 to 34 Children: 62 to 970 Children: 17 to 37 Adults: 28 to 95 Adults: 267 to 1,290 Adults: 19 to 74
Organic acidurias are a group of inheritable genetic metabolic disorders dueto a defect in protein metabolism where an essential enzyme is absent ormalfunctioningThis defect results in a build up of chemicals, in this case usually acids,on one side of the metabolic blockage and a deficiency of vital chemicals on theotherThis causes an over dosage of one chemical (often toxic) and the shortage ofanother which is essential to normal body functioning. Characteristics of the conditions include general malaise, reluctance to feed, breathing problems, vomiting, hypotonia (floppiness) and/or spasticity
2-Methyl-3-Hydroxybutyrl CoA Dehydrogenase deficiency(MHBD)• 2-Methylbutyrl CoA Dehydrogenase deficiency (2-MBCD)• 3-Hydroxy-3-Methylglutaryl CoA Lyase deficiency (HMG)• 3-Methylcrotonyl CoA Carboxyl deficiency (3-MCC)• 3-Methylglutaconyl CoA Hydratase deficiency (3-MGA)• Glutaric Aciduria Type I (GA-1)• Isobutyryl CoA Dehydrogenase deficiency (ICBD)• Isovaleric Acidemia (IVA)• Malonic Aciduria (MA)• Methylmalonic Acidemia (MMA)• Mitochondrial Acetoacetyl CoA Thiolase – (3-Ketothiolase) (BKT)• Multiple CoA Carboxylase (MCD)• Propionic Acidemia (PA)
Tandem MS Spectrophotometry Ascending and descending chromatography on paper, Thin-layer chromatography (TLC) (Ortho Dianisidine stain for organic acids and Ninhydrin stain for Aminoacids ) High voltage electrophoresis (HVE) on paper Colorimetric methods Gas chromatography (GC) HPLC Enzyme assays
Introduction The porphyrias are caused by deficiencies of enzymes involved in heme biosynthesis which lead to blockade of the porphyrin pathway and subsequent accumulation of porphyrins and their precursors.
Cutaneous features are not seen in acute intermittent porphyria (AIP) or the very rare aminolevulinic acid dehydratase (ALA-D) deficient porphyria. Erythropoieticprotoporphyria and congenital erythropoietic porphyria are characterized by porphyrins produced mainly in the bone marrow. The reminder are primarily hepatic porhyrias.
Excessive concentrations of porhyrins exposed to day-light generate free radicals, leading to cell membrane damage and cell death.
The type of cellular damage depends on the solubility and tissue distribution of the porphyrins. Two main patterns of skin damage are seen in the porphyries: 1. accumulation of water soluble uro- and coproporphyrins leads to blistering. 2. accumulation of the lipophilic protoporphyrins leads to burning sensations in the exposed skin.