Table 5 All IEMs (n = 29, 43%) requiring a specific ‘2 nd -tier’ test for diagnosis
Biochemical category | Disease | Diagnostic test |
|---|---|---|
Amino acids | PSAT deficiency | CSF amino acids (& PAA) |
| Â | PSPH deficiency (Serine deficiency) | CSF amino acids (& PAA) |
| Â | Late onset non-ketotic hyperglycinemia | CSF AA (& Plasma AA) |
| Â | 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 |
| Â | Creatine transporter deficiency | SLC6A8 gene sequencing |
Lipids | Abetalipoproteinemia | CBC smear, stool samples, fasting lipid profile, MTTP gene analysis |
Lysosomal | Krabbe disease | WBC enzyme testing |
| Â | Metachromatic leucodystrophy (MLD) | Arylsulfatase-A enzyme activity |
| Â | Niemann-Pick, type C | Filipin staining test (fibroblasts) & NPC1/NPC2 gene analyses |
Mitochondria | Coenzyme Q10 deficiency | Coenzyme Q10 (fibroblasts) & gene(s) analysis |
| Â | MELAS | Mitochondrial DNA mutation testing |
| Â | Pyruvate dehydrogenase deficiency | Blood & CSF lactate:pyruvate ratio (enzyme activity, gene(s) analysis) |
Neurotransmission | Aromatic-L-amino-acid decarboxylase deficiency | CSF biogenic amines |
| Â | DHPR deficiency (biopterin deficiency) | CSF neurotransmitters & biopterin loading test |
| Â | Dopamine transporter deficiency syndrome | CSF neurotransmitters |
| Â | GTPCH1-deficient dopa-responsive dystonia | CSF neurotransmitters & biopterin/Phe loading test; clinical trial of L-dopamine, GTCPH gene analysis |
| Â | PTPS deficiency (biopterin deficiency) | CSF neurotransmitters & biopterin loading test |
| Â | Sepiapterin reductase deficiency | CSF neurotransmitters & biopterin/Phe loading test |
| Â | Tyrosine hydroxylase deficiency | CSF neurotransmitters & TH gene analysis |
| Â | Vesicular monoamine transporter 2 (VMAT2) | CSF monoamine metabolites |
Urea cycle | Carbamoyl phosphate synthetase (CPS) deficiency | CPS gene analysis |
| Â | N-acetyl-glutamate synthetase deficiency | NAGS gene analysis |
Vitamins/Co-factors | Biotinidase deficiency | Biotinidase enzyme activity |
| Â | Biotin-thiamine-responsive basal ganglia disease | SLC19A3 gene analysis |
| Â | Cerebral folate deficiency syndrome | CSF tetrahydrofolate |
| Â | Hypermanganesemia with dystonia, polycythemia, and cirrhosis | Whole-blood manganese concentrations, SLC30A10 gene analysis |
|  | Pyridoxamine 5’-phosphate oxidase deficiency | Plasma, CSF |