Disorders

Metabolic Disorder Screening by the Urease Method

Diagnostic Carbohydrates, Organic or Amino Acids

Disorder and compound
*indicates isotope dilution available
Standard in Library
Standard Curve
Positive Control
Diagnosed
by MSL
DISORDERS OF AROMATIC AMINO ACID METABOLISM
Phenylketonuria

X 1
---Phenylpyruvic acid X X X
---Phenyllactic acid X
X
---2-Hydroxyphenylacetic acid X


Tyrosinemia



a. Transient neonatal, oculocutaneous, and hepatorenal forms

X 2
---4-Hydroxyphenylpyruvic acid X
X
---4-Hydroxyphenyllactic acid X
X
---4-Hydroxyphenylacetic acid X X X
---N-Acetyltyrosine X


b. Hepatorenal form only

X 2
---Succinylacetone X X X
Hawkinsinuria

X
---4-Hydroxycyclohexylacetic acid X
X
---5-Oxoproline X X X
---4-Hydroxyphenylpyruvic acid X
X
---4-Hydroxyphenyllactic acid X
X
Alcaptonuria

X 1
---Homogentisic acid X X X
DISORDERS OF BRANCHED CHAIN AMINO ACID METABOLISM
Maple syrup urine disease

X 4
---2-Oxoisocaproic acid X X X
---*2-Oxo-3-methylvaleric acid X X X
---2-Oxoisovaleric acid X X X
---2-Hydroxyisovaleric acid X X

---2-Hydroxyisocaproic acid X X

---2-Hydroxy-3-methylvaleric acid X
X
Dihydrolipoyl dehydrogenase (E3) deficiency



---*Lactic acid X X

---2-Oxoglutaric acid X


---2-Oxoisocaproic acid X X

---*2-Oxo-3-methylvaleric acid X X

---2-Oxoisovaleric acid X X

---2-Hydroxyisovaleric acid X


---2-Hydroxyisocaproic acid X


---2-Hydroxy-3-methylvaleric acid X


Isovaleric acidemia

X
---Isovalerylglycine X X X
---3-Hydroxyisovaleric acid X X X
---4-Hydroxyisovaleric acid X


3-Methylcrotonyl-CoA carboxylase deficiency

X
---3-Hydroxyisovaleric acid X X X
---3-Methylcrotonylglycine X X X
Biotin-responsive multiple carboxylase deficiency



a. Holocarboxylase synthetase deficiency

X
---3-Hydroxyisovaleric acid X X X
---3-Methylcrotonylglycine X X X
---Methylcitric acid X
X
---3-Hydroxypropionic acid X X X
---*Lactic acid X X X
b. Biotinidase deficiency

X
Same metabolities but generally smaller elevations



3-Methylglutaconic aciduria X
X
a. 3-methylglutaconyl-CoA hydratase deficiency



---3-Methylglutaconic acid X
X
---3-Hydroxyisovaleric acid X X X
---3-Methylglutaric acid X
X
b. Normal hydratase

X 1
---3-Methylglutaconic acid X
X
---3-Methylglutaric acid X
X
3-Hydroxy-3-methylglutaric aciduria

X 2
---3-Hydroxy-3-methylglutaric acid X
X
---3-Methylglutaconic acid X
X
---3-Methylglutaric acid X
X
---3-Hydroxyisovaleric acid X X X
---3-Methylcrotonylglycine X X X
3-Oxothiolase deficiency



a. Mitochondrial branched chain 3-oxothiolase deficiency

X
---2-Methyl-3-hydroxybutyric acid X


---2-Methylacetoacetic acid X


---Tiglylglycine X X

b. Cytosolic 3-oxothiolase deficiency or succinyl-CoA:



3-oxoacid CoA transferase deficiency



---*3-Hydroxybutyric acid X X X
---*Acetoacetic acid X X X
Propionic acidemia

X 3
---Methylcitric acid X
X
---3-Hydroxypropionic acid X X X
---Propionylglycine X X X
---3-Hydroxyvaleric acid X X X
Vitamin B12 deficiency X X X 1
Methylmalonic acidemia X X X 5
---*Methylmalonic acid X X X
---Methylcitric acid X
X
---3-Hydroxypropionic acid X X X
---Propionylglycine X X X
---3-Hydroxyvaleric acid X X X
Malonyl-CoA decarboxylase deficiency



---Malonic acid X X X
---*Methylmalonic acid X X X
DISORDERS OF DIBASIC AMINO ACID METABOLISM
2-Oxoadipic aciduria X


---2-Oxoadipic acid



---2-Hydroxyadipic acid X


---Glutaric aciduria type I X

1
Glutaric acid X X X
3-Hydroxyglutaric acid X
X
---Glutaconic acid

X
Hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome



---*Orotic acid X X X
Lysinuric protein intolerance X X X
---*Orotic acid



DISORDERS OF THE UREA CYCLE
N-Acetylglutamate synthetase: No abnormalities of organic acids



Carbamyl phosphate synthase deficiency



---Hippuric acid (due to treatment with benzoate)



Argininosuccinase deficiency



---*Orotic acid X X X
---Uracil X X X
Argininosuccinate synthase Deficiency


1
---*Orotic Acid



Orotidine Ornithine carbamoyltransferase deficiency

X 7
---*Orotic acid X X X
---Uracil X
X
Argininemia



---*Orotic acid X X

DISORDERS OF PYRIMIDINE METABOLISM
Orotic aciduria



---*Orotic acid X X

Dihydropyrimidine dehydrogenase deficiency



---Uracil X X

---Thymine X


DISORDERS OF FATTY ACID OXIDATION
Long chain acyl-CoA dehydrogenase deficiency


1
---Suberic acid X X X
---*Sebacic acid X X X
---Dodecanedioic and tetradecandioic acids may be present



Medium chain acyl-CoA dehydrogenase deficiency


5
---Octanoic acid X X X
---5-Hydroxyhexanoic acid X X X
---7-Hydroxyoctanoic acid X
X
---*Adipic acid X X X
---Suberic acid X X X
---Octenedioic acid X
X
---*Sebacic acid X X X
---Decenedioic acid X
X
---* Hexanoylglycine X X X
---Phenylpropionylglycine X X X
---Suberylglycine X X X
Short chain acyl-CoA dehydrogenase deficiency


X
---Ethylmalonic acid X X X
---Methylsuccinic acid X X X
---Dicarboxylic acids-variably elevated



Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II)


9
---Glutaric acid X X X
---Ethylmalonic acid X X X
---*Adipic acid X X X
---Suberic acid X X X
---2-Hydroxyglutaric acid X
X
---Isovalerylglycine X X X
---Isobutyrylglycine X
X
---2-Methylbutyrylglycine X
X
Short chain volatile acids may be elevated



Normals fed medium chain triglyceride formulas


Many
---*Adipic acid X X X
---Suberic acid X X X
---*Sebacic acid X X X
---5-Hydroxyhexanoic acid X
X
---7-Hydroxyoctanoic acid X
X
MISCELLANEOUS DISORDERS
Succinic semialdehyde dehydrogenase deficiency       1
4-Hydroxybutyric aciduria X X X 1
---4-Hydroxybutyric acid X X X
---3,4-Dihydroxybutyric acid X X X
Fumaric Aciduria

X 1
---Fumaric acid X X X
Mevalonic aciduria X
X
---Mevalonolactone X
X
---Mevalonic acid X
X
5-Oxoprolinuria X X X 1
---5-Oxoproline X X X
Canavan's disease

X 1
---N-Acetyl aspartic acid X X X
Dehydration



---*inositol X X X Hundreds
---mannitol X X X
Malabsorption Syndromes



---lactose X X X
---sucrose X X X
---*quinolinic acid X X X
Lactose intolerance



---Lactose

X Many
---3,4-dihydroxybutyric acid X X X
D-Glyceric aciduria

X
---D-Glyceric acid X X X
Hyperoxaluria type I

X 2
---*Oxalic acid



---*Glycolic acid



---Glyoxylic acid X X X
Hyperoxaluria type II

X
---*Oxalic acid X X X
---L-Glyceric acid X X X
Glycerol



---Glycerol X X X
Lactic acidoses Pyruvate dehydrogenase

X 1
---*Lactic acid X X X
---*Pyruvic acid X X X
---2-Hydroxybutyric acid X X X
---4-Hydroxyphenyllactic acid X
X
Intestinal bacterial overgrowth


Many
---D-Lactic acid X X X
---3-Hydroxypropionic acid X X X
---4-Hydroxyphenylacetic acid X X X
Hepatic failure

X Many
---phenylalanine X X X
---tryptophan X X X
---methionine X X X
---tyrosine X X X
---histidine X X X
Renal dysfunction

X Many
---threonine X X X
---serine X X X
---proline X X X
---glutamine X X X
---hydroxyproline X X X
Chronic hypoxia

X
---lactate, branch chain ketoacids X X X Many
Acidosis, gluconeogenesis

X
----ketoglutarate X X X Many
---malate X X X
---aspartate X X X
---glutamate X X X
AMINO ACID DISORDERS
Hyperlysinemia



---*lysine X X X
Arginosuccinase deficiency



---*Orotic acid X X X  
Citrullinemia



---*Orotic acid X X X
Hartnup disorder


1
Renal Fanconi's X X X 2
Histidinemia



---*Histidine X X X
Pyruvate carboxylase deficiency



---Alanine X X

Hyper- ß-alaninemia



---ß-alanine X X

Aminoadipic aciduria



Aminoadipic acid X


Ketoadipic acidura



----Ketoadipic acid X
X
ß-Aminoisobutyric aciduria


Hundreds
----ß-Aminoisobutyric acid X X X
Hyperornithinemia



---Ornithine X X

Cystinuria X X X 3
---*Lysine X X X
---Cystine X X X
Hyperdibasicaminoaciduria


Many (transient)
---*Lysine X X X
---Ornithine X X X
---Cystine X X X
Lysinuric protein intolerance


X
---Arginine X X X
---Glutamine X X X
---Lysine X X X
---Ornithine X X X
---*Orotic acid X X X
Dicarboxylic aminoaciduria



---N( ß-Aspartyl)lysinuria X


---Saccharopinuria X


---Cystathioninuria X X X 2-neonatal
---*Homocystinuria X X X
Ethanolaminosis X


---Ethanolamine X X X
Hyperglycinuria

X 1
---Glycine X X X
Hyperprolinemia type I, Prolidase deficiency X X X
---Proline X X X 1
Hydroxyprolinemia X X X
---Hydroxyproline

X
Tryptophanuria

X
---*Tryptophan X X

Lysine malabsorption

X
---*Lysine X X

Mercaptolactate-cysteine disulfiduria -



*Formiminoglutamic aciduria X X X 1
---Formiminoglutamic acid X X X
Hypermethioninemia X X X
Hypophosphatasia

X 1
---phosphoethanolamine X X X
Molybdenum cofactor deficiency/Sulfite oxidase deficiency

X 2
---Xanthine X X X
Glutathione synthase deficiency X X X
---pyroglutamic acid X X X 1
CARBOHYDRATES
Aspartylglucosaminura

X
---Aspartylglucosamine X
X
Galactosemia X X X 3
---Glucitol X X X
---Galactitol X X X
---Galactonic acid X X X
Renal glycosuria

X
---Glucose X X X 2
Hereditary fructose intolerance



---Fructose X X X
Sialic Acid Storage Disease

X
---N-acetyl neuraminic acid X X X
Pentosuria

X
---xylulose X


NEUROTRANSMITTERS
Pheochromocytoma/Neuroblastoma

X
---Vanilmandelic acid X X X
---Homovanillic acid X X X
---Purines & Pyrimidines



---2-deoxyadenosine X


TOXICOLOGIC
Aspirin Poisoning


1
---Salicylic acid X


---ß-hydroxybutyric acid X


---Salicylate glycine conjugate X


---Glutamic acid X


Tegretol Poisoning


1
---Adipic acid X


Carbamazepine diol



Valproate toxicity X     1
---Valproate glucuronide X


---Adipic acid X


---Alpha-ketoglutaric acid X