Table 1.
Markers of inherited and acquired disorders of propionate, cobalamin, and methionine metabolism, count of cases, and Collaborative Laboratory Integrated Reports (CLIR), tools.
| Disorder | Compl. Group | OMIM # | Gene | 1st Tier Markers | CLIR | 2nd Tier Markers | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| C3 | Met | * No. Cases | MS/MS Tool | Hcy | MMA | MCA | ||||
| Propionic acidemia | n/a | 606054 | PCA, PCB | High | N | 136 | PROP | N | N | High |
| Isolated Methylmalonic acidemia | mut0 mut- |
251000 | MCM | 192 | MUT/Cbl AB | N | High | High | ||
| Cbl A | 251100 | MMAA | ||||||||
| Cbl B | 251100 | MMAB | ||||||||
| Methylmalonic acidemia and Homocystinuria | Cbl C | 277400 | MMACHC | Low | 139 | Cbl CD | High | High | N to High | |
| Cbl D | 277410 | MMACHC | ||||||||
| Cbl F | 277380 | LMBRD1 | 3 | Cbl F | ||||||
| Cbl J | 614857 | ABCD4 | - | - | ||||||
| Cbl X | 309541 | HCFC1 | - | - | ||||||
| Intrinsic factor deficiency | n/a | 261000 | GIF | N | - | - | High | High | N to High | |
| Megaloblastic anemia-1 | 261100 | CUBN, AMN | - | - | ||||||
| Transcobalamin II deficiency | 275350 | TCN2 | - | - | ||||||
| Transcobalamin receptor defect | 613646 | CD320 | 11 | TCblR | ||||||
| Maternal Vitamin B12 deficiency | - | - | Low | 138 | B12 (mat) | |||||
| Homocystinuria (CBS deficiency) | n/a | 236200 | CBS | N | High | 74 | HCY | High | N | N |
| Homocystinuria and megaloblastic anemia | Cbl G | 250940 | MTR | Low | 11 | RMD | ||||
| Cbl E | 236270 | MTRR | ||||||||
| MTHFR deficiency | n/a | 236250 | MTHFR | |||||||
| Methionine adenosyltransferase def. | 250850 | MAT 1A | High | 112 | H-MET | N | N | N | ||
| Adenosine kinase deficiency | 180960 | ADK | ||||||||
| Glycine N-methyltransferase def. | 606664 | GNMT | ||||||||
| S-adenosylhomocysteine hydrolase def. | 613752 | AHCY | ||||||||
| FP C3 | n/a | n/a | High | N | 124 | FP C3 | N | N | N | |
| TPN | n/a | n/a | N | High | 2816 | TPN | N | N | N | |
* Count of CLIR cases as of January 31, 2020. Abbreviations as follows: C3, propionylcarnitine; Cbl, cobalamin; CBS, cystathione β-synthase; CLIR, Collaborative Laboratory Integrated Reports (see text); FP, false positive; Hcy, total homocysteine; High, elevated concentration in dried blood spots in >50% of cases; Low, reduced concentration in dried blood spots in >50% of cases; Met, methionine; MCA, 2-methylcitric acid; MMA, methylmalonic acid; mut, mutase; MTHFR, (N)5,10-methylenetetrahydrofolate reductase; n/a, not applicable; N, normal concentration in dried blood spots; N to High, inconsistent elevation in <50% of cases; RMD, remethylation disorders, OMIM #—Online Mendelian Inheritance in Man symbol indicating a descriptive entry, usually phenotype.