| α-AASA (a-amino-adipic semialdehyde) |
Neonatal epileptic seizures (usually with suppression-burst), or later pyridoxine-responsive epilepsy |
No need to obtain urine before giving pyridoxine or pyridoxal phosphate. May be only slightly raised. Do pipecolic acid also in plasma |
Pyridoxine-dependent epilepsy (PDE) due to α-AASA-dehydrogenase deficiency (see also Clinical Vignette 2.16.1) |
| Acylcamitines (plasma more useful) |
Acute metabolic encephalopathy (plasma better) |
Excretion ↑↑ by carnitine load (100mg/kg) except when enzyme defect confined to brain. May be difficult to interpret |
Specific acylcarnitines indicate particular disorders, e.g. octanoyl carnitine in MCAD deficiency, glutaryl carnitine in glutaric acidura type 1 (GA1) |
| Amino acids |
Learning disability, acute encephalopathy, intermittent ataxia, various syndromes including Lowe |
24-h sample not necessary. If unusual amino acid being sought (e.g. S-sulphocysteine in sulphite oxidase deficiency) discuss with laboratory |
Relate to dietary input. Significance of minor deviations from 'normal' uncertain. Abnormalities in amino-acidopathy, organic acidaemias, sulphite oxidase deficiency, renal tubular leak (including mitochondrial disorders, Wilson disease). 'False' aminoaciduria in GAMT deficiency |
| Bile acids |
Suspect peroxisomopathy |
Arrange with reference laboratory in advance. Random sample -freeze immediately |
Abnormal bile acids excreted in many peroxisomal disorders (especially single enzyme defects as D-bifunctional protein deficiency). Output declines with age so ± negative after early infancy |
| Copper |
Acquired movement disorder, acquired behaviour disorder ± abnormal liver function |
24-h urine. Meticulous attention to ensure copper-free containers and to prevent copper contamination |
Elevation = Wilson disease (false negative in 5%) |
| Creatine/creatinine ratio |
Boys with learning disability |
False positives possible if diet high in creatine (meat, oily fish) |
↑ in creatine transporter deficiency |
| 6AG (glycosaminoglycans, mucopolysaccharides - see also Oligosaccharides) |
Learning disability ± coarse features, corneal clouding, dysostosis. SpEEGh deterioration. Behavioural difficulties, especially aggression in Sanfilippo disease |
24-h collection for heparan sulphate if Sanfilippo likely and initial test for GAG is negative (and specific gene mutation analysis is not possible) |
Mucopolysaccharidoses will be detected, especially heparan sulphate in Sanfilippo disease. Excess possible in Lowe and Zellweger syndromes and in peroxisomopathies. False increase in GAMT deficiency |
| |
Regression at any age |
Wise to check leukocyte beta-galactosidase |
Keratan sulphate + increased in all forms of GM1 gangliosidosis |
| Guanidinoacetate (GAA) |
Language delay, early epilepsy, movement disorder |
H-MRS for creatine peak desirable |
↑ in GAMT deficiency. ↓1 in AGAT deficiency |
| VMA (HMMA). HVA (catecholamines) |
Acute or subacute cerebellar ataxia/myoc onus/opsoclonus |
Special diet no longer usually indicated; 24-h urine preferred (whole body imaging more reliable) |
Increase is consistent with occult neuroblastoma, but result is commonly normal when opsoclonus/myoclonus or other movement disorder is caused by neural crest tumour |
| VMA (HMMA), HVA (catecholamines) |
Early dystonia with oculogyric crises |
Avoid levodopa beforehand |
↓ in sepiapterin reductase deficiency |
| |
Neonatal hypothermia/failure to thrive |
Hair may be normal |
↑ HVA/VMA ratio in Menkes disease (>4.0) |
| Myoglobin |
Toddler-age encephalopathy with elevatec creatine kinase |
Random sample |
Rhabdomyolysis primary or secondary. Too many causes to list but include carnitine transport defects, fatty acid disorder that will need organic acid analysis and acylcarnitines and possibly muscle biopsy for diagnosis |
| Oligosaccharides |
Learning disability ± coarse features, corneal clouding, dysostosis. May be dysmorphic neonate, hydrops. Myoclonus epilepsy |
Random sample adequate |
Mucclipidoses detected in particular |
| Organic acids (easily recognizable organic acidaemias are not discussed) |
Developmental delay, learning disability, "cerebral palsy', macrocephaly, dystonia, chorea, encephalopathy (± epileptic seizures), regression, myelopathy. Rarely of value in 'pure' epilepsy |
Freeze urine immediately. Test during acute illness in a condition with episodes of encephalopathy (such as GA1). False positive with medium-chain triglyceride oil. False 1 in GAMT deficiency |
Specific patterns of acids may suggest diagroses: glutaric (GA1); glutaric, ethylmalonic, adipic (GA2); L-2-hydroxyglutaric(L-2-hydroxyglutaric aciduria); N-acetylaspartic (Canavan disease); 4-hydroxybutyric (SSADH deficiency); methylmalonic (cobalamin disorders) |
| Orotic acid |
III neonate.. Vomiting-headache-impaired consciousness complex. 'Stroke'. ↓ ammonia |
Random sample. Interpretation should be by metabolic expert |
If ↑= ornithine transearbamylase deficiency, hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome, and other rare pyrimidine synthesis defects. If in doubt, repeat after protein load under expert supervision |
| Oxalic acid |
Dysmorphism, developmental delay, hypotonia |
Add HCI as preservative |
Peroxisomopathies |
| Phosphate |
5uspected mitochondrial disorder |
Plasma phosphate necessary for formula |
Reduced phosphate reabsorption = tubular dysfunction |
| Porphyrins |
Acquired motor neuropathy ± convulsive seizures ± abdominal colic (at puberty) |
Random sample, then 24-h urine |
Excess excretion leads to specific tests for acute intermittent porphyria |
| Pteridines |
Delay, seizures, dystonia ± fluctuation |
Phenylalanine may be only mildly ↑ in plasma |
Biopterin % of pterins: ↓ biopterin synthesis defects (most commonly PTPS deficiency). ↑ DHPR deficiency |
| Sialic acid (free) |
Features of infantile free sialic acid storage disease (see literature for further details) |
Single urine. Screen for oligosaccharides will not detect free sialic acid |
All patients show vacuolated lymphocytes. 10- to 20-fold increase in sialic acid storage disease. 100-fold increase in sialuria |
| Succinyl purines (Bratton-Marshall trst) |
Neonatal seizures, delay, autism, Angelman-like, + dysmorphism |
Freeze random morning urine; purine reference laboratory will confirm |
↑ in adenylosuccinate lyase deficiency. ↓ in AICA (5-amino-4-imidazolecarboxamide) ribosiduria |
| Sulphatides |
Suspect metachromatic leukodystropy (MLD) |
Urinary sediment. Important to test if arylsulphatase A (ARSA) low in case pseudodeficiency |
↑ in all cases of MLD including those with normal ARSA but activator protein (saposin-B) deficiency |
| Sulphite |
Neonatal encephalopathy |
Stix test must be done immediately on freshly passed urine. Bag urine not suitable. Repeat as often as necessary if diagnosis strongly suspected (but may be true negatives) |
May be positive in molybdenum cofactor deficiency or sulphite oxidase deficiency. Quantatitive determination of sulphite by anion column chromatography is necessary |
| Uracil |
Childhood encephalopathy |
Blood ammonia ± urine orotic acid may be normal |
↑ in late-onset ornithine transcarbamylase (OTC) deficiency |
| Urate |
Early seizures ± opisthotonus. Early acquired movement disorder with motor delay and high or high-normal plasma urate. Ataxic cerebral palsy ('dysequilibrium-diplegia') |
24h urine preferable. Urine urate is more sensitive than plasma urate estimation |
↑ output = Lesch-Nyhan syndrome or similar disorder. ↓ excretion = deficiency of molybdenum cofactor or purine nucleoside phosphorylase |
