TABLE 3.
Biochemical presentation of PA and conditions with raised methylmalonic acid
| Organic acids in urine | Acylcarnitines in dried blood or plasma | Plasma | |||||
|---|---|---|---|---|---|---|---|
| Methylmalonic acid | 3‐hydroxy‐propionate | 2‐methylcitrate | Propionylcarnitine | Homocysteine | Vitamin B12 | Holotranscobalamin | |
| Diseases discussed in these guidelines | |||||||
| MMA a | ↑‐↑↑↑ | ↑ | ↑ | ↑↑ | n | n | n |
| PA | n | ↑ | ↑(↑) | ↑↑ (↑) | n | n | n |
| Other defects and deficiencies causing raised methylmalonic acid | |||||||
| MCEE deficiency | ↑ | (↑) | (↑) | (↑) | n | n | n |
| ACSF3 deficiency b | ↑ | n | n | n | n | n | n |
| Adenosyl‐ and methylcobalamin synthesis defects c | ↑ ‐ ↑↑↑ | ↑ | ↑ | ↑‐↑↑ | ↑ ‐ ↑↑↑ | n | n |
| Transcobalamin deficiency | ↑ | n‐↑ | n‐↑ | n‐↑ | ↑ | n‐↓ | ↓ |
| Transcobalamin receptor deficiency | ↑ | n/a | n/a | n/a | n‐↑ | n/a | n/a |
| IF deficiency and Imerslund‐Najman‐Gräsbeck syndrome | ↑ ‐ ↑↑ | n‐↑ | n‐↑ | n‐↑ | ↑ ‐ ↑↑ | ↓↓ | ↓ |
| Nutritional vitamin B12 deficiency | ↑ ‐ ↑↑ | n‐↑ | n‐↑ | n‐↑ | ↑ ‐ ↑↑ | ↓‐↓↓ | ↓‐↓↓ |
Note: Pathognomonic biochemical findings for MMA and PA in urine and blood compared to other related diseases, causing raised methylmalonic acids levels. Isolated defects in the methylcobalamin pathway are not displayed.
Abbreviations: ACSF3, acyl‐CoA synthetase family member 3; IF, intrinsic factor; MCEE, methylmalonyl CoA epimerase; MMA, methylmalonic acidaemia; n, normal; n/a, no data available; PA, propionic acidaemia.
a
Subtypes mut, cblA, cblB, cblD‐MMA.
b
In addition to methylmalonic acid, raised malonic acid can be found in urine; biochemical parameters based on Reference 6.
c
Subtypes cblC, cblD‐MMA/HC, cblF, cblJ.