Table 2 Laboratory investigation of mitochondrial fatty acid oxidation disorders (FAOD).
From: Improving diagnosis of mitochondrial fatty-acid oxidation disorders
Laboratory tests | Specimen type | Special conditions for sampling | Expected abnormalities in FAOD |
|---|---|---|---|
Routine tests | |||
Glucose | Plasma or serum | Acute episode | <3 mmol/L |
Ketone bodies | Urine: dipstick Blood: enzymatic measurement or blood metre | Acute episode Blood immediately deproteinised if enzymatic measurement | When glycaemia <3 mmol/L - Urine < ++ - Blood <1 mmol/L |
Ammonia | Plasma | Acute episode Blood brought on ice within 10 min to the laboratory for testing | >100 μmol/L (mainly new-borns and infants) |
Transaminases (ASAT, ALAT) | Plasma or serum | Acute episode | ASAT > ALAT ASAT, ALAT > 200 UI/L |
Lactic acid | Blood | Acute episode | >2 mmol/L |
Creatine kinase (CK) | Plasma or serum | Acute episode | >1000 UI/L |
Complete cell count | Blood (EDTA) | Anaemia (CTD) | |
Insulin C-peptide | Plasma | Acute episode | When glycaemia <3 mmol/L - Insulin ≥2 mUI/L (SCHAD) - C-peptide ≥165 pmol/L) |
When the patient is in non-catabolic clinical conditions, results for routine tests in the range of controls do not exclude a FAOD | |||
Biochemical genetic tests | |||
Acylcarnitine profile | Plasma or dried blood spot (DBS) | Acute episode or fasting state: in adults >14 hours (mandatory), in children depends on age | - CTD: ↓ C0 and all acylcarnitines - CPT IA: ↑ C0 ↓ C16 C18:1 (dried blood spot) - CPT II, CACT (early onset): ↑ C12 C14 C16 C18:1 C16-DC C18:1-DC - CPT II (late onset): ↑ C16 C18:1 (plasma) - LCHAD / MTP: ↑ C14-OH C16 C16-OH C18:1 C18:1-OH C18-OH - VLCAD: ↑ C14:1 C16 C18:1 - MCAD: ↑ C6 C8 C10:1 C10 (C8/C10>2) - MAD, riboflavin disorders (mainly FAD synthase, MFT): ↑ C4 C5 C6 C8 C10 C5-DC C12 C14 C16 C18:1 (possibly not all acylcarnitines) - SCAD: ↑ C4 - SCHAD: ↑ C4-OH |
Free and total carnitine | Plasma Urine if plasma free carnitine <5 μmol/L | - CTD: plasma free and total carnitine <5 μmol/L, urine free and total carnitine >5 mmol/mol of creatinine - Other FAOD except CPT IA: in general, plasma free carnitine <20 μmol/L, total-free carnitine >15 μmol/L - CPT IA: plasma free carnitine >50 μmol/L in DBS (can be normal in plasma) Plasma carnitine levels in the range of controls do not exclude a FAOD | |
Organic acid profile | Urine | Acute episode or fasting state | - All FAOD: saturated and unsaturated dicarboxylic acids +/− 3-hydroxydicarboxylic acids - MCAD: same all FAOD + hexanoylglycine, suberylglycine, phenylpropionylglycine - MAD, riboflavin disorders (mainly FAD synthase, MFT): same MCAD + isobutyrylglycine, 2-methylbutyrylglycine, isovalerylglycine, ethylmalonic acid, 2-hydroxyglutaric acid +/− glutaric acid - SCAD: ethylmalonic acid, methylsuccinic acid +/− butyrylglycine - SCHAD: 3-hydroxyglutaric acid A normal urinary organic acid profile does not exclude a FAOD |
In vitro flux studies | Blood Intact cultured skin fibroblasts | Blood sample must reach the laboratory in less than 48 hours Contact the laboratory for skin biopsy conditions | Abnormal de novo synthesis of 2H-acylcarnitines from 2H-palmitate and L-carnitine or decreased oxidation rate of 3H or 14C labelled fatty acids |
Specific enzyme activity measurement | Limited number of laboratories in the world | Performed if the pathogenicity of the identified variant(s) has not been demonstrated | |
Molecular genetic tests | |||
Single gene (Sanger method) | Blood (EDTA). Eventually frozen tissues (muscle, liver, …) or cultured skin fibroblasts | Detection of pathogenic variants (homozygous or compound heterozygous) | |
Gene panel (Next Generation Sequencing [NGS]) | |||
Whole exome or genome sequencing (ultra-high throughput sequencing) | |||
