From: Treatment with metformin in twelve patients with Lafora disease
Clinical Features | Pre-Treatment Assessment | Metformin Treatment | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Pt | Age (y), Sex | Onset age (y) | Mutationa | Disease duration (y) | Concomitant AEDs | No. GTCS (last 28 days) | Myoclonusb | Disability scalec | Maximal dose (mg), adjusted dose (mg) | Outcome | Duration (months) | Adverse events |
1 | 17d, F | 13 | EPM2A: c.491 T > G (p.Ile164Ser), c.539 T > C (p.Leu180Pro) | 4 | VPA, ZNS, PB | 0e | +++ | 4 | 3000, 1500 | Mild improvement (see text) | 6 | Diarrhoea |
2 | 21, M | 16 | NHRLC1: c.436G > A (p.Asp146Asn), c.1133 T > C (p.Leu378Pro) | 4 | VPA, LEV, PERf, CNZ, CLB | 18 | + | 3 | 2000, 1000 | Seizure-freedom, improved cognition, lasted for 6 months | 9 | Diarrhoea |
3g | 25, F | 13 | EPM2A: c.243_246del (p.Asp82Argfs*7) | 10 | VPA, LEV, ZNS, PB, CNZ | 3 | +++ | 4 | 500, 500 | Disease progression | 12h | None |
4g | 19, F | 10 | NHLRC1: c.205C > G (p.Pro69Ala); c.826_829dup (p.Ala277Aspfs*23) | 7 | VPA, LEV, ZNS, CNZ | 6 | +++ | 4 | 1000, 500 | Disease progression | 24 | Asthenia |
5 | 17,F | 13 | NHLRC1: c.205C > G (p.Pro69Ala) | 3 | VPA, LEV, PER, CNZ | 8 | +++ | 4 | 2000, 2000 | Disease progression | 13 | None |
6 | 23, M | 14 | EPM2A: c.721C > T (p.Arg241*) | 7 | LEV, TPM, ZNS | 7 | +++ | 4 | 2000, 2000 | Disease progression | 9h | Elevated CPK, muscle cramps |
7 | 23, M | 10 | EPM2A: c.721C > T (p.Arg241*) | 11 | VPA, PB, PHT, PER, CNZ | 11 | +++ | 3 | 2000, 2000 | Disease progression | 28 | None |
8 | 18, M | 14 | NHLRC1: c.992del (p.Gly331Glufs*3) | 2 | VPA, LEV, PER | 2 | ++ | 2 | 1700, 500 | Disease progression | 26 | Diarrhoea |
9 | 22, F | 13 | NHLRC1: c.992del (p.Gly331Glufs*3) | 7 | VPA, ZNS, PER | 3 | +++ | 4 | 1700, 500 | Disease progression | 26 | Diarrhoea |
10 | 50, F | 18 | EPM2A: c.721C > T (p.Arg241*), c.835G > A (p.Gly279Ser) | 29 | VPA, LEV, ZNS, CNZ | 1 | +++ | 4 | 1000, 1000 | Mild improvement (see text) | 36 | None |
11 | 19, F | 11 | EPM2A: c.323G > T (p.Arg108Leu) | 7 | VPA, PB, PER, CNZ | 0.5 | +++ | 4 | 1000, 1000 | Disease progression | 12 | None |
12 | 18, M | 13 | NHLRC1: c.436G > A (p.Asp146Asn), c.1133 T > C (p.Leu378Pro) | 4 | VPA, LEV, ZNS, PB | 3 | ++ | 3 | 1500, 1500 | Disease progression | 12 | None |