Aminoaciduria
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Transcript of Aminoaciduria
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 involved
Acidic aminoacids
Acidic aminoaciduria
Glutamate, Aspartate
Basic amino acids and cystine
Cystinuria Cystine, lysine, arginine, ornithine
Lysinuric protein intolerance
Lysine, arginine, ornithine
Isolated cystinuria
Cystine
Lysinuria Lysine
Major categories
Forms Amino acids involved
Neutral amino acids
Hartnup disease Alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine
Blue diaper syndrome
Tryptophan
Iminoglycinuria Glycine, proline, hydroxyproline
Glycinuria Glycine
Methioninuria Methionine
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 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 from defects in the basolateral transport of dibasic amino acids but not cystine
Hartnup disease involves a neutral amino acid transport system in both the kidney and intestineBlue diaper syndrome involves a kidney-specific tryptophan transporter Methioninuria appears to involve a separate methionine transport system in the proximal tubuleIminoglycinuria and glycinuria are clinically benign disorders
Alanine
Children: 65 to 190
Adults: 160 to 690
Carnosine
Children: 34 to 220
Adults: 16 to 125
Hydroxyproline
Children: not measured
Adults: not measured
Alpha-aminoadipic acid
Children: 25 to 78
Adults: 0 to 165
Citrulline
Children: 0 to 13
Adults: 0 to 11
Isoleucine
Children: 3 to 15
Adults: 4 to 23
Arginine
Children: 10 to 25
Adults: 13 to 64
Cystine
Children: 11 to 53
Adults: 28 to 115
Leucine
Children: 9 to 23
Adults: 20 to 77
Asparagine
Children: 15 to 40
Adults: 34 to 100
Glutamic acid Children: 13 to 22
Adults: 27 to 105
Lysine
Children: 19 to 140
Adults: 32 to 290
Aspartic acid
Children: 10 to 26
Adults: 14 to 89
Glutamine
Children: 150 to 400
Adults: 300 to 1,040
Methionine Children: 7 to 20
Adults: 5 to 30
In micromoles per deciliter (micromol/dL)
Ornithine
Children: 3 to 16
Adults: 5 to 70
Proline
Children: not measured
Adults: not measured
Threonine
Children: 25 to 100
Adults: 80 to 320
Phenylalanine
Children: 20 to 61
Adults: 36 to 90
Serine
Children: 93 to 210
Adults: 200 to 695
Tyrosine
Children: 30 to 83
Adults: 38 to 145
Beta-alanine
Children: 0 to 42
Adults: 0 to 93
Glycine Children: 195 to 855
Adults: 750 to 2,400
1-methylhistidine Children: 41 to 300 Adults: 68 to 855
Beta-amino-isobutyric acid
Children: 25 to 96
Adults: 10 to 235
Histidine
Children: 46 to 725
Adults: 500 to 1,500
3-methylhistidine Children: 42 to 135 Adults: 64 to 320
Phosphoserine
Children: 16 to 34
Adults: 28 to 95
Taurine
Children: 62 to 970
Adults: 267 to 1,290
Valine
Children: 17 to 37
Adults: 19 to 74
Organic acidurias are a group of inheritable genetic metabolic disorders due to a defect in protein metabolism where an essential enzyme is absent or malfunctioningThis 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 the otherThis causes an over dosage of one chemical (often toxic) and the shortage of another 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)
Selected Organic Acidurias and Associated Organic Acid ElevationsSelected Organic Acidurias and Associated Organic Acid Elevations
Organic AciduriaOrganic Aciduria Elevated Organic AcidElevated Organic Acid
Methylmalonic acidemiaMethylmalonic acidemia Methylmalonic acid, methylcitric acid,Methylmalonic acid, methylcitric acid,3-hydroxypropionic acid, propionylglycine,3-hydroxypropionic acid, propionylglycine,3-hydroxyvaleric acid3-hydroxyvaleric acid
Fatty oxidation defects (medium chain acyl-Fatty oxidation defects (medium chain acyl-CoA dehydrogenase deficiency [MCAD])CoA dehydrogenase deficiency [MCAD])
Adipic acid, suberic acid, sebacic acid, octanoic Adipic acid, suberic acid, sebacic acid, octanoic acid, suberylglycine, hexanoylglycine, acid, suberylglycine, hexanoylglycine, octenedioic acid, phenylpropionylglycine, octenedioic acid, phenylpropionylglycine, 5-hydroxyhexanoic acid5-hydroxyhexanoic acid
Propionic acidemiaPropionic acidemia Propionylglycine, methylcitric acid,Propionylglycine, methylcitric acid,3-hydroxypropionic acid, 3-hydroxyvaleric 3-hydroxypropionic acid, 3-hydroxyvaleric acidacid
Glutaric aciduria, type 1Glutaric aciduria, type 1 Glutaric acid, glutaconic acid, 3-hydroxyglutaric Glutaric acid, glutaconic acid, 3-hydroxyglutaric acidacid
Multiple acyl-CoA dehydrogenase Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria, type II)deficiency (glutaric aciduria, type II)
Glutaric acid, adipic acid, suberic acid,Glutaric acid, adipic acid, suberic acid,2-hydroxyglutaric acid, ethylmalonic acid, 2-hydroxyglutaric acid, ethylmalonic acid, isovalerylglycineisovalerylglycine
Isovaleric acidemiaIsovaleric acidemia Isovalerylglycine, 3-hydroxyisovaleric acidIsovalerylglycine, 3-hydroxyisovaleric acid
Multiple carboxylase deficiencyMultiple carboxylase deficiency 3-Methylcrotonylglycine, methylcitric acid, 3-Methylcrotonylglycine, methylcitric acid, lacticlacticacid, 3-hydroxyisovaleric acid, tiglylglycine,acid, 3-hydroxyisovaleric acid, tiglylglycine,3-hydroxypropionic acid3-hydroxypropionic acid
Urea cycle defectsUrea cycle defects Orotic acidOrotic acid
Maple syrup urine disease (MSUD)Maple syrup urine disease (MSUD) 2-Oxoisocaproic acid, 2-hydroxyisocaproic 2-Oxoisocaproic acid, 2-hydroxyisocaproic acid,acid,2-hydroxyisovaleric acid, 2-oxoisovaleric 2-hydroxyisovaleric acid, 2-oxoisovaleric acid,acid,2-hydroxy-3-methylvaleric acid,2-hydroxy-3-methylvaleric acid,2-oxo-3-methylvaleric acid2-oxo-3-methylvaleric acid
Lactic acidosisLactic acidosis Lactic acid, pyruvic acid, 2-hydroxybutyric acid,Lactic acid, pyruvic acid, 2-hydroxybutyric acid,4-hydroxyphenyllactic acid4-hydroxyphenyllactic acid
TyrosinemiaTyrosinemia 4-Hydroxyphenyllactic acid, 4-4-Hydroxyphenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenylpyruvic acid, N-hydroxyphenylpyruvic acid, N-acetyltyrosine, succinylacetone (type I only)acetyltyrosine, succinylacetone (type I only)
Canavan diseaseCanavan disease N-acetylaspartic acidN-acetylaspartic acid
KetosisKetosis Acetoacetic acid, 3-hydroxybutyric acid, adipic Acetoacetic acid, 3-hydroxybutyric acid, adipic acid, suberic acid, 3-hydroxyisobutyric acid, suberic acid, 3-hydroxyisobutyric acid,acid,3-hydroxyisovaleric acid, 3-hydroxy-2-3-hydroxyisovaleric acid, 3-hydroxy-2-methylbutyric acidmethylbutyric acid
Phenylketonuria (PKU)Phenylketonuria (PKU) Phenyllactic acid, phenylpyruvic acid,Phenyllactic acid, phenylpyruvic acid,2-hydroxyphenylacetic acid2-hydroxyphenylacetic acid
2-Oxoadipic aciduria2-Oxoadipic aciduria 2-Oxoadipic acid, 2-hydroxyadipic acid2-Oxoadipic acid, 2-hydroxyadipic acid
3-Hydroxy-3-methylglutaric aciduria 3-Hydroxy-3-methylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine, 3-methylglutaconicacid, 3-methylglutaric acid
3-Methylcrotonyl-CoA carboxylase deficiency
3-Hydroxyisovaleric acid, 3-methylcrotonylglycine
3-Methylglutaconic aciduria 3-Methylglutaconic acid, 3-hydroxyisovaleric acid,3-methylglutaric acid
3-Oxothiolase deficiency 3-Hydroxy-2-methylbutyric acid, tiglylglycine,
2-methylacetoacetic acid, acetoacetic acid,
3-hydroxybutyric acid
5-Oxoprolinuria 5-Oxoproline
Dihydrolipoyl dehydrogenase deficiency (lipoamide dehydrogenase, E3)
Lactic acid, 2-hydroxyisocaproic acid,2-hydroxyisovaleric acid, 2-hydroxy-3-methylvaleric acid, 2-oxoglutaric acid, 2-oxoisocaproic acid,2-oxoisovaleric acid, 2-oxo-3-methylvaleric acid
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
PorphyriasPorphyrias
IntroductionIntroduction
The porphyrias are caused by deficiencies The porphyrias are caused by deficiencies of enzymes involved in heme biosynthesis of enzymes involved in heme biosynthesis which lead to blockade of the porphyrin which lead to blockade of the porphyrin pathway and subsequent accumulation of pathway and subsequent accumulation of porphyrins and their precursors.porphyrins and their precursors.
Classification of porphyriasClassification of porphyrias
Cutaneous features are not seen in acute Cutaneous features are not seen in acute intermittent porphyria (AIP) or the very rare intermittent porphyria (AIP) or the very rare aminolevulinic acid dehydratase (ALA-D) aminolevulinic acid dehydratase (ALA-D) deficient porphyria. deficient porphyria.
Erythropoietic protoporphyria and congenital Erythropoietic protoporphyria and congenital erythropoietic porphyria are characterized erythropoietic porphyria are characterized by porphyrins produced mainly in the bone by porphyrins produced mainly in the bone marrow. The reminder are primarily marrow. The reminder are primarily hepatic porhyrias. hepatic porhyrias.
Excessive concentrations of porhyrins Excessive concentrations of porhyrins exposed to day-light generate free exposed to day-light generate free radicals, leading to cell membrane radicals, leading to cell membrane damage and cell death. damage and cell death.
The type of cellular damage depends on The type of cellular damage depends on the solubility and tissue distribution of the the solubility and tissue distribution of the porphyrins. Two main patterns of skin porphyrins. Two main patterns of skin damage are seen in the porphyries:damage are seen in the porphyries:
1.1. accumulation of water soluble uro- and accumulation of water soluble uro- and coproporphyrins leads to blistering.coproporphyrins leads to blistering.
2.2. accumulation of the lipophilic protoporphyrins accumulation of the lipophilic protoporphyrins leads to burning sensations in the exposed leads to burning sensations in the exposed skin. skin.
InvestigationInvestigation