Patient 1, female, 12.5 y | Patient 2, female, 15.5 y | Patient 3, male, 26 m | Patient 4, male, 30 y | |
PROSC mutation (RefSeq accession NM_007198.3) | c.[119C>T];[722G>A] p.[(Pro40Leu)];[(Arg241Gln)] | c.[249_252del];[614G>A] p.[(Ser84Cysfs*21)];[(Arg205Gln)] | c.[260C>T];[260C>T] p.[(Pro87Leu)];[(Pro87Leu)] | c.[206A>G];[206A>G] p.[(Tyr69Cys)];[(Tyr69Cys)] |
Consanguinity; ethnicity | No; Swiss-Italian | No; German | Yes; Arabic | Yes; Italian |
Anomalies during pregnancy | No | No | No | No |
Gestational age in weeks | 40 | 38 | 37 | 40 |
Birth weight/length/HC | 3620 g/51 cm/35 cm (50–75th PC) | 2940 g/49 cm/35 cm (50–75th PC) | 3325 g/NA/NA | 4350 g/NA/36 cm (50th PC) |
APGAR; pH | 6/7/8; NA | 10/10/10; pH 7.36 | 5/10; NA | 10/10/10; NA |
Perinatal metabolic anomalies | NR | NR | NR | NR |
Anaemia | No | No | NR | NR |
Seizure onset | Day 7 | Day 6 | Day 3 | Day 9 |
Seizure type, semiology | Myoclonia, grimacing, eye deviation | Cloni of arms and legs | Tonic-clonic, bilateral | Tonic head and eye deviation |
EEG at onset | Slightly abnormal background activity | Discontinuity, multifocal SW activity | Right frontotemporal SW activity | Burst suppression pattern |
Antiepileptics before vitamin B6 | Phenobarbitone | Phenobarbitone | Phenobarbitone, Levetiracetam, Valproate, ACTH | Phenobarbitone, Nitrazepam |
Age at first vitamin B6 administration | Day 28 | Day 7 | Day 30 | Day 31 |
Dosage and vitamer at first administration | Pyridoxine 100 mg i.v. | Pyridoxine 100 mg i.v. | Pyridoxine 100 mg i.v. | Pyridoxine 100 mg i.v. |
Vitamin B6 effect | Prompt cessation of seizures | No effect on EEG (seizures controlled on phenobarbitone) | Prompt cessation of seizures | Prompt cessation of seizures |
Side effects of first vitamin B6 administration | Prolonged sleep, muscle hypotonia | None | None | None |
Course of epilepsy | Breakthrough seizures during fever | Single febrile and afebrile seizures, last at age 14 y | Sporadic afebrile tonic-clonic seizures (about 1/ m) | Photosensitive seizures from age 6 y |
Vitamin B6 withdrawal | Yes, age 14 m - encephalopathic | Yes, age 11 y – vertigo, severe headache, numbness of hands | Not performed | Not performed |
Current dose of vitamin B6 p.o. | Pyridoxine 300 mg/day in 2 SD | Pyridoxine 150 mg/day in 2 SD | Pyridoxine 450 mg/day in 4 SD | Pyridoxine 300 mg/day in 3 SD |
Other anticonvulsants | No | No | No | Valproate (15 mg/kg/day) |
Last EEG | Normal at age 12 y | No epileptic discharges, intermittent slowing at age 13 y | Occasional occipital SW at age 25 m | Normal at age 27 y |
Cranial imaging | cMRI at age 12 days normal | cUS normal, cMRI at age 13 y normal | cUS normal, cMRI at age 12 and 24 m normal | cMRI at age 17 y normal |
Developmental milestones | Normal | Slightly delayed | Delayed | Normal |
Independent sitting at | 7 m | 10 m | 20 m | NA |
Independent walking at | 13 m | 15 m | Pending | 12 m |
Speech development | Normal | Normal | Absent | Normal |
School performance or IQ | Sixth class grammar school, excellent | Ninth class grammar school, good | - | Learning difficulties |
Current HC | 55 cm (75–90th PC) | 55 cm (75–90th PC) | 50.5 cm (50–75th PC) | 56 cm (50th PC) |
APGAR Score is a quick test performed at 1, 5, and 10 min after birth to assess vital parameters of the newborn with a maximum score of 10.
ACTH, Adrenocorticotropic hormone; cMRI, cerebral MRI; HC, head circumference; i.v., intravenous; m, months; NA, not available; NR, not recorded; PC, percentile; p.o., peroral; SD, single dosage; SW, spike wave; US, ultrasound; y, years.