TABLE 2.

Suggested screening for inborn errors of metabolism (IEM) according to clinical suspicion

The clinical similarities between many IEM makes it appropriate to cast a wide net as part of initial screening*.26 The first step should involve a review of newborn dried blood spot results (screened disorders vary among health systems). Thereafter, appropriate tests, depending on clinical suspicion, may include:

Suspected small molecule “intoxication” disorder

Serum ammonia level (may be normal outside of crises, especially in partial deficiency).

Urine organic acid analysis (detection of organic acidemias and some fatty acid oxidation defects)

Plasma and urine amino acids

Serum lactate

Suspected small molecule “energy deficit” disorder

Serum ketones and glucose (often both low during acute FAOD presentations)

Serum free fatty acids (FAOD)

Plasma acylcarnitine profile and serum free and total carnitines (low in disorders of carnitine transport)

Serum lactate:pyruvate ratio taken 1 hour after feeding (mitochondrial respiratory chain defects)27

Cerebrospinal fluid lactate, pyruvate, amino acids and protein27

Serum thymidine (especially in MNGIE)27

mtDNA genetic testing

Tissue analysis may be necessary to seal the diagnosis27

Suspected disorder of “complex molecule” metabolism

Lysosomal enzyme testing (most lysosomal storage disorders)

Plasma oxysterols (Niemann Pick type C)

Serum very long chain fatty acid, pristanic acid and phytanic acid analyses (peroxisomal disorders)

^*Many of these tests are optimally performed after an overnight fast.²⁶ Testing should be interpreted by a metabolic specialist, as it is oftentimes the pattern of abnormality, rather than the absolute individual values, which suggest the diagnosis.²⁸

IEM, Inborn errors of metabolism; FAOD, fatty acid oxidation defects; MNGIE, mitochondrial neurogastrointestinal encephalopathy; mtDNA, mitochondrial DNA.