A protein metabolism disorder where excess amino acids are present in the urine can be either primary or secondary aminoaciduria, with primary due to enzyme defects in amino acid metabolism and secondary due to defects in amino acid transporters in the kidney and intestine. Major categories include acidic, basic, cystine, neutral and branched chain amino acids. Diagnosis involves measuring urine amino acid levels using techniques like thin layer chromatography, high voltage electrophoresis, and tandem mass spectrometry.

2. 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

3. Major categories Forms Amino acids
involved
Acidic aminoacids Acidic aminoaciduria Glutamate, Aspartate
Basic amino acids and Cystinuria Cystine, lysine,
cystine arginine, ornithine
Lysinuric protein Lysine, arginine,
intolerance ornithine
Isolated cystinuria Cystine
Lysinuria Lysine

4. Major Forms Amino acids involved
categories
Neutral 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

5. 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 from
defects in the basolateral transport of dibasic amino acids but not
cystine

6. Hartnup disease involves a neutral amino acid transport system in both the
kidney and intestine
Blue diaper syndrome involves a kidney-specific tryptophan transporter
Methioninuria appears to involve a separate methionine transport system in
the proximal tubule
Iminoglycinuria and glycinuria are clinically benign disorders

7. 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 measured
Alpha-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 23
Arginine 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 77
Asparagine 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 290
Aspartic 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

8. Ornithine Proline Threonine
Children: 3 to 16 Children: not Children: 25 to 100
Adults: 5 to 70 measured Adults: 80 to 320
Adults: not measured
Phenylalanine 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 145
Beta-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 2,400
Beta-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 1,500
Phosphoserine 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

9. Organic acidurias are a group of inheritable genetic metabolic disorders due
to a defect in protein metabolism where an essential enzyme is absent or
malfunctioning
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 the
other
This 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

11. 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)

12. Selected Organic Acidurias and Associated Organic Acid Elevations
Organic Aciduria Elevated Organic Acid
Methylmalonic acidemia Methylmalonic acid, methylcitric acid,
3-hydroxypropionic acid, propionylglycine,
3-hydroxyvaleric acid
Fatty oxidation defects (medium chain acyl- Adipic acid, suberic acid, sebacic acid, octanoic
CoA dehydrogenase deficiency [MCAD]) acid, suberylglycine, hexanoylglycine,
octenedioic acid, phenylpropionylglycine, 5-
hydroxyhexanoic acid
Propionic acidemia Propionylglycine, methylcitric acid,
3-hydroxypropionic acid, 3-hydroxyvaleric
acid
Glutaric aciduria, type 1 Glutaric acid, glutaconic acid, 3-hydroxyglutaric
acid
Multiple acyl-CoA dehydrogenase deficiency Glutaric acid, adipic acid, suberic acid,
(glutaric aciduria, type II) 2-hydroxyglutaric acid, ethylmalonic acid,
isovalerylglycine
Isovaleric acidemia Isovalerylglycine, 3-hydroxyisovaleric acid
Multiple carboxylase deficiency 3-Methylcrotonylglycine, methylcitric acid, lactic
acid, 3-hydroxyisovaleric acid, tiglylglycine,
3-hydroxypropionic acid

13. Urea cycle defects Orotic acid
Maple 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 acid
Lactic acidosis Lactic acid, pyruvic acid, 2-hydroxybutyric acid,
4-hydroxyphenyllactic acid
Tyrosinemia 4-Hydroxyphenyllactic acid, 4-
hydroxyphenylacetic acid, 4-
hydroxyphenylpyruvic acid, N-
acetyltyrosine, succinylacetone (type I only)
Canavan disease N-acetylaspartic acid
Ketosis Acetoacetic acid, 3-hydroxybutyric acid, adipic
acid, suberic acid, 3-hydroxyisobutyric acid,
3-hydroxyisovaleric acid, 3-hydroxy-2-
methylbutyric acid
Phenylketonuria (PKU) Phenyllactic acid, phenylpyruvic acid,
2-hydroxyphenylacetic acid
2-Oxoadipic aciduria 2-Oxoadipic acid, 2-hydroxyadipic acid

14. 3-Hydroxy-3-methylglutaric aciduria 3-Hydroxy-3-methylglutaric acid, 3-
hydroxyisovaleric acid, 3-methylcrotonylglycine,
3-methylglutaconic
acid, 3-methylglutaric acid
3-Methylcrotonyl-CoA carboxylase 3-Hydroxyisovaleric acid, 3-
deficiency 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 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

15.  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

16. Porphyrias

17. 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.

19. Classification of porphyrias

20.  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.

21.  Excessive concentrations of porhyrins
exposed to day-light generate free
radicals, leading to cell membrane
damage and cell death.

22.  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.

24. Investigation