Table 2.
Clinical and genetic findings of patients with MAT I/III deficiencies; summary of reported cases
| Subtype | MAT1A mutations | No. of family (number of pts or carriers) | Plasma methionine (μmol/L) | Plasma homocysteine (μmol/L) | Clinical outcome | In vitro expression (% of wild type) | Ref. |
|---|---|---|---|---|---|---|---|
| AR | p.[Leu355Arg];[Leu355Arg] | 1 (1) | 485 | 21 | Normal | NA | (6) |
| AR | p.[Thr288Ala];[Thr288Ala] | 1 (1) | 899 | 23.1 | Normal | NA | (6) |
| Carrier | p.[Thr288Ala] | 1 (1) | 59.2 | NA | Normal | NA | |
| Carrier | p.[Arg199Cys] | 1 (1) | 25 | NA | Normal | 11.1 | (6) |
| AR | p.[Glu57Lys];[Gln245Profs*20] | 1 (1) | 461 | <13.5 | Normal | NA/NA | (7) |
| AR | c.[IVS2-2A>G];p.[Arg292Cys] | 1 (1) | 938 | <13.5 | Normal | NA/18 | (7) |
| AR | p.[Val230Met];[Arg356Pro] | 1 (1) | 328 | <13.5 | Normal | NA/10 | (7) |
| AR | p.[Arg356Gln];[Arg356Gln] | 1 (1) | 592 | <13.5 | Normal | 53.1/53.1 | (7) |
| AR | p.[Glu145Lys];[Arg292Cys] | 1 (1) | 766 | 36 | Myelination delay | NA/∼18 | (7) |
| AR | p.[Arg292Cys];[Arg356Leu] | 1 (1) | 395–1,676 | <13.5 | Transient myelination arrest, epilepsy | ∼18/NA | (7) |
| AR | p.[Arg356Gln];[Gly378Ser] | 1 (1) | 254–400 | NA | Normal | 53.1/0.17 | (11) |
| AR | p.[Ala276Glyfs*76]; [Ala276Glyfs*76] | 1 (1) | 600–1,400 | NA | Dyspraxia, demyelination, calcification of basal ganglia, headache, fine nystagmus,diadokokinesis | NA | (11) |
| AR | p.[splicing];[Arg199Cys] | 1 (1) | 1,544–1,685 | NA | Abnormal | NA/11 | (11) |
| AR | p.[Tyr92His];[Arg356Pro] | 2 (3) | 402–2,250 | <13.5–37.4 | White matter lesion (1 pt), demyelination (3 pt), normal development (3 pt) | 100/10 | (12,24) |
| AR | p.[Ser180Leufs*6];[Trp274Ser] | 1 (1) | 216–1,457 | NA | Normal | NA/NA | (13) |
| AR | p.[Ile322Met];[Ile322Met] | 1 (1) | 100–1,270 | NA | Normal | 45.8/45.8 | (14) |
| AR | p.[leu305pro];[Ile322Met] | 1 (1) | 364–583 | NA | Normal | 26/45.8 | (14) |
| AR | p.[Ala55Asp];[Pro357Leu] | 1 (1) | 315–1,020 | NA | Normal | 17.2/31 | (14) |
| AR | p.[Met64Lys];[Pro197Leufs*26] | 1 (1) | 134–1,567 | 45.5 | Normal | NA | (16) |
| Carrier | p.[Met64Lys] | 1 (1) | 36.3 | NA | Normal | NA | |
| Carrier | p.[Pro197Leufs*26] | 1 (1) | 14.9 | NA | Normal | NA | |
| AR | p.[Arg264Cys];[Pro357Leu] | 1 (1) | 648 | 5.43 | Normal | 0.3/ 31 | (17) |
| AR | p.[Pro357Leu];[Pro357Leu] | 1 (1) | 305 | 9.76 | Normal | 31 | (17) |
| AR | p.[Arg356Pro];[Pro357Leu] | 1 (1) | 622 | 7 | Normal | ∼10/31 | (17) |
| AR | p.[Gly69Ser];[*396Tyr] | 1 (1) | 1560 | 15 | Normal | 100/NA | (17) |
| AR | p.[Ile37Thr];[Gly91Ser] | 1 (1) | 86.5–406 | 13.57 | Normal | NA/NA | (18) |
| AR | p.[Arg299Cys];[Arg299Cys] | 1 (1) | 1,067–1,426 | NA | Hypomyelination, anomalous signals in the gray matter and a heterogeneous hyposignal from the posterior part of the basal ganglia | 18/18 | (19) |
| AR | p.[Gly381Arg];[Gly381Arg] | 1 (1) | 1,378–1,884 | NA | Normal | ∼30/∼30 | (19) |
| AR | p.[Gly279Val];[Ile322Val] | 1 (1) | 596 | NA | Normal | NA/∼1 | (19) |
| AR | p.[Ala297Asp];[Ser180Leufs*6] | 1 (2) | 1,549–1,614 | NA | Developmental delays, especially of speech | 20/NA | (19,24) |
| AR | p.[Arg356Trp];[Arg356Trp] | 1 (1) | 1,846 | NA | Severely retarded | ∼3/∼3 | (19,24) |
| AR | p.[Arg299his];[Arg299His] | 3(5) | 641–1,634 | NA | Developmental delay and myoclonic epilepsy (1 pt), prolonged relaxation time in MR and normal development (1 pt) dysdiadochokinesis (1 pt) | ∼17/∼17 | (19,24) |
| AR | p.[Ser22Leu];[Ser22Leu] | 1 (1) | 850–1,100 | 30–45 | Normal | 52/52 | (19,27) |
| AR | p.[Leu42Pro];[Leu42Pro] | 1 (1) | 390–2,070 | 59 | Normal | ∼10/10 | (19,27) |
| AR | p.[Gly378Ser];[Trp387*] | 1 (2) | 1,089–1,243 | 19.7–28.6 | Normal | 0.2/75 | (22) |
| Carrier | p.[Gly378Ser] | 1 (1) | 11 | NA | Normal | 0.2 | |
| AR | p.[Trp387*];[Trp387*] | 1 (1) | 16–23 | NA | Normal | 75/75 | |
| AR | p.[Val230Gly];[Val230Gly] | 1 (2) | 518–525(838) | NA | Normal | NA | (24) |
| AR | p.[Leu176Gln];[Leu176Gln] | 1 (1) | 57–200 | NA | Normal | NA | (24) |
| AR | p.[Asp286Asn];exons 6-8 del | 1 (1) | 106–1,570 | NA | Normal | NA/NA | (24) |
| AR | p.[Arg177Trp]; [Arg177Trp] | 1 (1) | 97–641 | NA | Normal | NA | (24) |
| AR | c.[169 + 1G>A];[169 + 1G>A] | 1 (1) | 860–1,130 | NA | Normal | NA | (24) |
| AR | p.[Arg199His];[Arg199His] | 1 (1) | 118–208 | NA | Normal | NA | (24) |
| AR | p.MAT1Adel;MAT1Adel | 1 (1) | 192–1,608 | NA | White matter lesions | NA | (24) |
| AR | p.[Ile203del];[Ile203del] | 1 (1) | 148–1,490 | NA | White matter change, speech delay | NA | (24) |
| AR | p.[Arg312Trp;[Arg312Trp] | 1 (1) | 460–1,437 | NA | White matter lesions, delayed myelination, IQ78 | NA | (24) |
| AR | p.[Gly98Arg];[Gly98Arg] | 1 (1) | 507–1,012 | NA | White matter change, delayed myelination | NA | (24) |
| AR | p.[Lys351*];[Lys351*] | 1 (1) | unknown | NA | Delayed myelination | NA | (24) |
| AR | p.[Gln246Profs*20];[Arg264Cys] | 1 (1) | 938–1,271 | NA | White matter lesions, delayed myelination | NA/0.3 | (24) |
| AR | p.[Ser180Leufs*6]; [Ser180Leufs*6] | 2 (2) | 686–2,541 | 5–24.9 | Normal | NA | (25) |
| AR | p.[Ser180Leufs*6]; p.[Arg199Cys] | 1 (1) | 759–1,467 | 19.3 | Normal | NA/11.1 | (25) |
| AR | p.[Val348Glyfs*3];[Val348Glyfs*3] | 1 (1) | 1,114–1,629 | NA | MR, dystonia, demyelination | NA | (25) |
| AR | p.[IVS3-1G>A];[IVS3-1G>A] | 1 (1) | 1,226–1,664 | 47.5 | Delay of early gross motor, diffusely abnormal white matter and patchy basal ganglia bilaterally, demyeliniation, Deterioration by pyridoxine treatment | NA | (3,25) |
| AR | p.[Arg264Cys];[Gly336Arg] | 1 (1) | 1,721–1,870 | 15.1 | Borderline mentality | 0.3/22.9 | (25) |
| Carrier | p.[Arg264Cys] | 1 (1) | 30 | NA | Normal | 0.3 | |
| AR | p.[Ser38Asn];[Thr86Hisfs*8] | 1 (1) | 770–1,240 | NA | Demyelination | 0/NA | (25) |
| AR | p.[Arg199Cys];[Arg199Cys] | 2 (3) | 374–902 | 7.7–8.6 | Normal | 11.1/11.1 | (25) |
| AR | p.[Ile322Met];[Glu344Ala] | 1 (1) | 185–467 | NA | Normal | 45.8/12.1 | (25) |
| AD | p.[Arg264His] | 53 (131) | 32–666 | 7.3–22.8 | Myelination abnormality (1 pt ), normal (130 pts) | 0.1 | (4–9,11, 14,17,18) |
NA, not available; MR, mental retardation.