Plasma carnitines Free, total, and acylated carnitine Primary and secondary carnitine deficiency; abnormal in many organic acid and fatty acid disorders
Urine organic acid profile Organic acids Organic acid, mitochondrial and fatty acid disorders
Urine oligosaccharide chromatography Glycosaminoglycans, Lysosomal storage disorders mucopolysaccharides
MSUD, Maple syrup urine disease; PKU, phenylketonuria.
The urine amino acid profile is helpful in diagnosing primary disorders of renal tubular function, such as Lowe syndrome and cystinuria, as well as secondary disorders of renal tubular function, such as cystinosis and Fanconi syndrome of any cause. The urine amino acid profile is not the test of choice for diagnosing disorders of amino acid or organic acid metabolism.
Markers of disordered fatty acid oxidation are measuredin urine and plasma. Excessive intermediates of fatty acidoxidation and organic acid catabolism are conjugated withglycine and carnitine. The urine acylglycine profile and the plasma acylcarnitine profile reflect this accumulation. In organic acid disorders and fatty acid oxidation disorders,measurement of plasma carnitine may reveal a secondarydeficiency of carnitine and abnormal distribution of free and acylated carnitine. The plasma free fatty acid profileis helpful in diagnosis of disorders of fatty acid oxidation.Excess 3-OH-butyrate suggests a disorder of ketone metabolism; absence of ketones or decreased amounts of 3-OHbutyrate suggests a fatty acid oxidation disorder. Profiling offatty acid intermediates in cultured skin fibroblasts may beinformative.
Disorders of organic acid metabolism, such as propionic acidemia and methylmalonic acidemia, have typical urine organic acid profiles. Although analysis of blood and urine usually suggest the specific diagnosis, more targeted testing is typically needed by measuring enzymatic activity in the pathway or establishing DNA changes in the gene.
Disorders of creatine biosynthesis are reflected by a reduction in creatine in cerebrospinal fluid (CSF) and, in one form, an increase in guanidinoacetic acid in blood and urine. Disorders of purine and pyrimidine metabolism are suggested bythe presence of an abnormal urinary profile of purines, suchas xanthine, hypoxanthine, inosine, guanosine, adenosine, adenine, or succinyladenosine. Similarly, disorders of pyrimidinemetabolism are identified by an abnormal profile of pyrimidines, including uracil, uridine, thymine, thymidine, orotic acid, orotidine, dihydrouracil, dihydrothymine, pseudouridine,N-carbamoyl-β-alanine, or N-carbamoyl-β-aminoisobutyrate, in the urine.
Storage disorders show abnormalities in urine mucopolysaccharides (glycosaminoglycans, glycoproteins), sialic acid, heparan sulfate, dermatan sulfate, or chondroitin sulfate. Specific enzymology depends on the disorder; tissue can be either white blood cells or cultured skin fibroblasts, depending on assay. In several disorders, CSF is the most helpful specimen, including glycine encephalopathy (CSF amino acid profile when compared to concurrent plasma amino acids), disorders of neurotransmitter synthesis (biogenic amine profile), glucose transporter (GLUT1) deficiency (plasma-to–cerebrospinal fluid glucose ratio), and serine synthesis defect (amino acid profile).
In many disorders, an abnormal metabolic profile is consistently present during illness and when the child is well. In some cases, it is only diagnostic during an episode of illness.