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Table 5 All IEMs (n = 29, 43%) requiring a specific ‘2 nd -tier’ test for diagnosis

From: Treatable inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review

Biochemical category Disease Diagnostic test
Amino acids PSAT deficiency CSF amino acids (& PAA)
  PSPH deficiency (Serine deficiency) CSF amino acids (& PAA)
  Late onset non-ketotic hyperglycinemia CSF AA (& Plasma AA)
  PHGDH deficiency (Serine deficiency) CSF AA (& Plasma AA)
Cerebral glucose transport Blood brain-barrier glucose-transporter (GLUT1) defect CSF glucose:plasma glucose ratio
Creatine Arginine: glycine amidinotransferase (AGAT) deficiency GATM gene sequencing
  Creatine transporter deficiency SLC6A8 gene sequencing
Lipids Abetalipoproteinemia CBC smear, stool samples, fasting lipid profile, MTTP gene analysis
Lysosomal Krabbe disease WBC enzyme testing
  Metachromatic leucodystrophy (MLD) Arylsulfatase-A enzyme activity
  Niemann-Pick, type C Filipin staining test (fibroblasts) & NPC1/NPC2 gene analyses
Mitochondria Coenzyme Q10 deficiency Coenzyme Q10 (fibroblasts) & gene(s) analysis
  MELAS Mitochondrial DNA mutation testing
  Pyruvate dehydrogenase deficiency Blood & CSF lactate:pyruvate ratio (enzyme activity, gene(s) analysis)
Neurotransmission Aromatic-L-amino-acid decarboxylase deficiency CSF biogenic amines
  DHPR deficiency (biopterin deficiency) CSF neurotransmitters & biopterin loading test
  Dopamine transporter deficiency syndrome CSF neurotransmitters
  GTPCH1-deficient dopa-responsive dystonia CSF neurotransmitters & biopterin/Phe loading test; clinical trial of L-dopamine, GTCPH gene analysis
  PTPS deficiency (biopterin deficiency) CSF neurotransmitters & biopterin loading test
  Sepiapterin reductase deficiency CSF neurotransmitters & biopterin/Phe loading test
  Tyrosine hydroxylase deficiency CSF neurotransmitters & TH gene analysis
  Vesicular monoamine transporter 2 (VMAT2) CSF monoamine metabolites
Urea cycle Carbamoyl phosphate synthetase (CPS) deficiency CPS gene analysis
  N-acetyl-glutamate synthetase deficiency NAGS gene analysis
Vitamins/Co-factors Biotinidase deficiency Biotinidase enzyme activity
  Biotin-thiamine-responsive basal ganglia disease SLC19A3 gene analysis
  Cerebral folate deficiency syndrome CSF tetrahydrofolate
  Hypermanganesemia with dystonia, polycythemia, and cirrhosis Whole-blood manganese concentrations, SLC30A10 gene analysis
  Pyridoxamine 5’-phosphate oxidase deficiency Plasma, CSF
  1. The IEMs are listed per biochemical category, with the specific biochemical/genetic diagnostic test per disease. Abbreviations include: CSF cerebrospinal fluid, PAA plasma amnio acids, Phe phenylalanine.
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172