TABLE 2.
Identified biomarkers in samples of patients with a confirmed neurometabolic diagnosis
| Diagnosis (OMIM) | n | Biomarker(s) | CSF | Plasma | Age‐dependent in CSF? a |
|---|---|---|---|---|---|
| Isovaleric acidemia (243500) | 1 | Isovalerylcarnitine | ↑↑ | ↑↑ | No (q = 0.52) |
| Isovalerylglycine | ↑ b | ↑↑↑ | ND d | ||
| 3‐Hydroxyisovaleric acid | ↓↓ c | ↓ c | No (q = 0.89) | ||
| Succinic semialdehyde dehydrogenase deficiency (271980) | 2 | 4‐Hydroxybutyric acid | ↑↑↑/↑↑↑ | ↑↑↑/NA | Yes (q = 1.7E−04) |
| N‐acetylneuraminate synthase deficiency (610442) | 1 | N‐acetylmannosamine | ↑↑ | ↑ | Yes (q = 7.1E−03) |
| Dihydropyrimidinase deficiency (222748) | 1 | Dihydrothymine | ↑↑ | ↑↑ | Yes (q = 0.017) |
| Dihydrouracil | ↑ | ↑ | Yes (q = 0.039) | ||
| Thymine | ↑↑↑ | ↑↑↑ | ND d | ||
| Uracil | ↑ b | ↑ | ND d | ||
| Aromatic l‐amino acid decarboxylase deficiency (608643) | 2 | 3‐Methoxytyrosine | ↑↑/↑ c | NA/NA | Yes (q = 6.3E−09) |
| 5‐Hydroxytryptophan | ↑ c /↑ | NA/NA | Yes (q = 6.7E−05) | ||
| 5‐Hydroxyindoleacetic acid | ↓ c /↓ c | NA/NA | Yes (q = 2.5E−10) | ||
| Homovanillic acid | ↓ c /↓↓ c | NA/NA | Yes (q = 1.5E−07) |
Note: Arrows indicate increased (↑) or decreased (↓) intensity of the indicated feature in the patient sample compared with controls. One arrow: fold change 1‐10, two arrows: fold change 10‐100, three arrows: fold change >100.
Abbreviations: n, number of patients; NA, not analyzed; ND, not determined.
a
Based on q‐values (=FDR‐adjusted P‐values) from the 30 IEM metabolite subanalysis.
b
Observed and abnormal in raw data but not observed in aligned data.
c
Not selected by standard statistical testing, corrected P‐value >.05.
d
Intensity in controls is too low for semiquantitative analysis.