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A protein metabolism disorder where excess amino acids are present in the urine         Primary aminoaciduria         Seco...
Major categories Forms                         Amino acids                                               involvedAcidic am...
Major           Forms                  Amino acids involvedcategoriesNeutral amino   Hartnup disease        Alanine, aspar...
Acidic aminoaciduria involves the transport of glutamate and aspartateIt results from a defect in the high-affinity sodi...
Hartnup disease involves a neutral amino acid transport system in both thekidney and intestineBlue diaper syndrome invol...
In micromoles per deciliter (micromol/dL)Alanine                       Carnosine                   Hydroxyproline     Chil...
Ornithine                    Proline                      Threonine     Children: 3 to 16             Children: not       ...
Organic acidurias are a group of inheritable genetic metabolic disorders dueto a defect in protein metabolism where an es...
2-Methyl-3-Hydroxybutyrl CoA Dehydrogenase deficiency(MHBD)• 2-Methylbutyrl CoA Dehydrogenase deficiency (2-MBCD)• 3-Hydro...
Selected Organic Acidurias and Associated Organic Acid ElevationsOrganic Aciduria                              Elevated Or...
Urea cycle defects                 Orotic acidMaple syrup urine disease (MSUD)   2-Oxoisocaproic acid, 2-hydroxyisocaproic...
3-Hydroxy-3-methylglutaric aciduria      3-Hydroxy-3-methylglutaric acid, 3-                                         hydro...
 Tandem MS Spectrophotometry Ascending and descending chromatography on paper, Thin-layer chromatography (TLC) (Ortho D...
Porphyrias
Introduction The porphyrias are caused by deficiencies of enzymes involved in heme biosynthesis which lead to blockade of...
Classification of porphyrias
 Cutaneous   features are not seen in acute intermittent porphyria (AIP) or the very rare aminolevulinic acid dehydratase...
 Excessive  concentrations of porhyrins exposed to day-light generate free radicals, leading to cell membrane damage and ...
   The type of cellular damage depends on    the solubility and tissue distribution of the    porphyrins. Two main patter...
Investigation
Aminoaciduria
Aminoaciduria
Aminoaciduria
Aminoaciduria
Aminoaciduria
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Aminoaciduria

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Transcript of "Aminoaciduria"

  1. 1. 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
  2. 2. 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
  3. 3. Major Forms Amino acids involvedcategoriesNeutral amino Hartnup disease Alanine, asparagine, glutamine,acids histidine, isoleucine, leucine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine Blue diaper syndrome Tryptophan Iminoglycinuria Glycine, proline, hydroxyproline Glycinuria Glycine Methioninuria Methionine
  4. 4. Acidic aminoaciduria involves the transport of glutamate and aspartateIt results from a defect in the high-affinity sodium potassium– dependent glutamate transporterIt is a clinically benign disorderCystine 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 cystinuriaThe rarer disorder, lysinuric protein intolerance, results fromdefects in the basolateral transport of dibasic amino acids but notcystine
  5. 5. Hartnup disease involves a neutral amino acid transport system in both thekidney and intestineBlue diaper syndrome involves a kidney-specific tryptophan transporterMethioninuria appears to involve a separate methionine transport system inthe proximal tubuleIminoglycinuria and glycinuria are clinically benign disorders
  6. 6. 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
  7. 7. 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
  8. 8. Organic acidurias are a group of inheritable genetic metabolic disorders dueto a defect in protein metabolism where an essential enzyme is absent ormalfunctioningThis 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 theotherThis 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
  9. 9. 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)
  10. 10. Selected Organic Acidurias and Associated Organic Acid ElevationsOrganic Aciduria Elevated Organic AcidMethylmalonic acidemia Methylmalonic acid, methylcitric acid, 3-hydroxypropionic acid, propionylglycine, 3-hydroxyvaleric acidFatty oxidation defects (medium chain acyl- Adipic acid, suberic acid, sebacic acid, octanoic CoA dehydrogenase deficiency [MCAD]) acid, suberylglycine, hexanoylglycine, octenedioic acid, phenylpropionylglycine, 5- hydroxyhexanoic acidPropionic acidemia Propionylglycine, methylcitric acid, 3-hydroxypropionic acid, 3-hydroxyvaleric acidGlutaric aciduria, type 1 Glutaric acid, glutaconic acid, 3-hydroxyglutaric acidMultiple acyl-CoA dehydrogenase deficiency Glutaric acid, adipic acid, suberic acid, (glutaric aciduria, type II) 2-hydroxyglutaric acid, ethylmalonic acid, isovalerylglycineIsovaleric acidemia Isovalerylglycine, 3-hydroxyisovaleric acidMultiple carboxylase deficiency 3-Methylcrotonylglycine, methylcitric acid, lactic acid, 3-hydroxyisovaleric acid, tiglylglycine, 3-hydroxypropionic acid
  11. 11. Urea cycle defects Orotic acidMaple syrup urine disease (MSUD) 2-Oxoisocaproic acid, 2-hydroxyisocaproic acid, 2-hydroxyisovaleric acid, 2-oxoisovaleric acid, 2-hydroxy-3-methylvaleric acid, 2-oxo-3-methylvaleric acidLactic acidosis Lactic acid, pyruvic acid, 2-hydroxybutyric acid, 4-hydroxyphenyllactic acidTyrosinemia 4-Hydroxyphenyllactic acid, 4- hydroxyphenylacetic acid, 4- hydroxyphenylpyruvic acid, N- acetyltyrosine, succinylacetone (type I only)Canavan disease N-acetylaspartic acidKetosis Acetoacetic acid, 3-hydroxybutyric acid, adipic acid, suberic acid, 3-hydroxyisobutyric acid, 3-hydroxyisovaleric acid, 3-hydroxy-2- methylbutyric acidPhenylketonuria (PKU) Phenyllactic acid, phenylpyruvic acid, 2-hydroxyphenylacetic acid2-Oxoadipic aciduria 2-Oxoadipic acid, 2-hydroxyadipic acid
  12. 12. 3-Hydroxy-3-methylglutaric aciduria 3-Hydroxy-3-methylglutaric acid, 3- hydroxyisovaleric acid, 3-methylcrotonylglycine, 3-methylglutaconic acid, 3-methylglutaric acid3-Methylcrotonyl-CoA carboxylase 3-Hydroxyisovaleric acid, 3-deficiency methylcrotonylglycine3-Methylglutaconic aciduria 3-Methylglutaconic acid, 3-hydroxyisovaleric acid, 3-methylglutaric acid3-Oxothiolase deficiency 3-Hydroxy-2-methylbutyric acid, tiglylglycine, 2-methylacetoacetic acid, acetoacetic acid, 3-hydroxybutyric acid5-Oxoprolinuria 5-OxoprolineDihydrolipoyl dehydrogenase deficiency Lactic acid, 2-hydroxyisocaproic acid,(lipoamide dehydrogenase, E3) 2-hydroxyisovaleric acid, 2-hydroxy-3- methylvaleric acid, 2-oxoglutaric acid, 2- oxoisocaproic acid, 2-oxoisovaleric acid, 2-oxo-3-methylvaleric acid
  13. 13.  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
  14. 14. Porphyrias
  15. 15. 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.
  16. 16. Classification of porphyrias
  17. 17.  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.
  18. 18.  Excessive concentrations of porhyrins exposed to day-light generate free radicals, leading to cell membrane damage and cell death.
  19. 19.  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.
  20. 20. Investigation
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