Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

Abstract

Incidental reports suggest that antenatal treatment of pyridoxine dependent seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two families with PDS are reported, both with two affected siblings. Antenatal treatment with pyridoxine was instituted during the second pregnancy in each family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively). Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12 (Family B) years of age were compared between the untreated and treated child within each family. Meconium-stained amniotic fluid was present in both first pregnancies and abnormal foetal movements were noticed in one. In the treated infants, pregnancy and birth were uncomplicated. In family A, postnatal pyridoxine supplementation prevented neonatal seizures. Both children in family A were hypotonic and started walking after 2 years of age; both had white matter changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in the antenatally untreated and treated child, respectively. The second child in family B developed seizures on the seventh day, because pyridoxine maintenance therapy had not been instituted after birth. Seizures responded rapidly to pyridoxine supplementation. MRI showed large ventricles and a mega cisterna magna. IQ was 80 and 106 in the antenatally untreated and treated child respectively. Both children had normal motor development. These results suggest that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDS.

The genotypic and phenotypic spectrum of pyridoxine‐dependent epilepsy due to mutations in ALDH7A1

“…Analysis of the outcome of patients homozygous for the same common severe mutation E399Q can reflect this impact. Some patients with this mutation can have substantial developmental delay and seizures that are not completely controlled with pyridoxine (group 3; e.g., Bennett et al 2009, patient K3020), whereas two other patients homozygous for this same mutation but treated prenatally with a high dose of pyridoxine had a normal developmental outcome (Bok et al 2010) (group 1). Yet, prenatal treatment with pyridoxine alone does not completely protect against developmental delay (Rankin et al 2007) reflecting additional complexity beyond prenatal treatment alone.…”

“…One possibility could be a deficiency limited to a region or a specific cell type in the brain. Direct toxicity of α-amino adipic semialdehyde binding to proteins or abnormalities in GABA metabolism have been proposed (Bok et al 2010; Gospe 2002). The activity of α-aminoadipic semialdehyde dehydrogenase on other substrates such as betaine aldehyde and trans -2-nonenal opens the possibility of other contributing toxic substances (Brocker et al 2010).…”

A rare case of pyridoxine-dependent seizures in infancy

“…suggested that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDE. [16]…”

Prenatal pharmacotherapy for fetal anomalies: a 2011 update

“…More recently, another disorder of amino acid synthesis was treated prenatally with apparent success in two families affected by pyridoxine-dependent seizures (Bok et al ., 2010). Maternal oral treatment with pyridoxine was given during the second pregnancy in each family and outcomes were compared with the first untreated pregnancy.…”