TABLE 3.
Biomarkers with possible utility as surrogate endpoints for PA or MMA
| Biomarker | Disorder | Matrix | Clinical relevance | References |
|---|---|---|---|---|
| MCA | PA/MMA | Plasma | MCA predicts disease burden, long‐term complications, and impact of organ transplantation | 13 |
| MCA:citric acid | PA/MMA | Plasma | Indicator for disease course and/or severity | 18 |
| C3 | PA/MMA | Plasma | C3 (measured as C3/C2) increases by up to ~20‐fold in patients with PA/MMA | 16 |
| Methylmalonic acid | MMA | Plasma | Elevation associated with risk for kidney disease and metabolic stroke | 20 |
| Ammonium | PA/MMA | Plasma | Repeated and frequent episodes of hyperammonemia can result in impaired growth and intellectual disability | 46 |
| FGF21/GDF15 | PA/MMA | Plasma | Elevation predicts long‐term complications | 13, 55 |
| Higher in patients with severe vs mild PA; lower in patients with PA after liver transplant | 17 | |||
| Concentration correlates with disease subtype, growth indices, and markers of mitochondrial dysfunction and is not affected by kidney disease | 58 | |||
| 13C‐propionate oxidation | PA/MMA | Breath | Decreased in MMA or PA; larger decreases correlate with more severe disease | 43 |
| Significantly higher in transplanted than non‐transplanted patients with PA, MMA | 43 |
Abbreviations: C2, acetylcarnitine; C3, propionylcarnitine; FGF21, fibroblast growth factor 21; GDF15, growth differentiation factor 15; MCA, methylcitric acid; MMA, methylmalonic acidemia; PA, propionic acidemia.