Researchers at University College and Great Ormond Street Hospital for Children, London, and other centers in the UK and Europe investigated the genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (PDE) by measurement of urinary alpha-aminoadipic semialdehyde (a-AASA) concentration and mutational analysis of the ALDH7A1 gene that encodes antiquitin. Twenty-one new patients with elevated AASA and 37 individuals from 30 families with mutations in ALDH7A1 were identified; 17 of these were novel and all others were published previously. The clinical spectrum of antiquitin deficiency and pyridoxine-dependent epilepsy includes ventriculomegaly, abnormal fetal movements, multisystem neonatal disorder, and seizures and autistic features after the first year of life. Presenting features included metabolic acidosis, respiratory distress, hypotonia, food intolerance, prematurity and fetal distress. Electrolyte derangements sometimes associated may include hypocalcemia and hypomagnesaemia, and endocrine disturbances include hypothyroidism and diabetes insipidus. Neurodevelopmental outcome is impaired in the majority of cases. Diagnosis of pyridoxin dependent epilepsy is sometimes challenging because seizures are responsive to anticonvulsant drugs in 38% cases, response to pyridoxin may not be instant and obvious in 14%, and structural brain abnormalities sufficient to explain the epilepsy may coexist.

Seizure types were clonic (91%), myoclonic jerks (62%) and tonic (44%). EEG abnormalities included burst suppression (21%) and hypsarrythmia (5%). Some movement disorders were dystonic and not associated with EEG changes. MRI abnormalities included cortical dysplasia, corpus callosal agenesis, and hydrocephalus, requiring v-p shunt. Biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine are recommended in infants and children with epilepsy and a variety of clinical features. A clinical trial of pyridoxine should be continued for a minimum of 72 hours, with careful clinical and EEG monitoring. [1]

COMMENT. In neonates and infants with intractable seizures, measurement of urinary alpha-aminoadipic semialdehyde and DNA tests for antiquitin deficiency should be performed to exclude pyridoxin-dependent epilepsy (PDE), regardless of an associated electrolyte disorder or structural abnormality on brain MRI. Diagnosis may be challenging because the seizures are sometimes partially controlled by anticonvulsant drugs, and the response to pyridoxine may be delayed. In classical cases of PDE, seizures occur in the first month, often within hours of birth. They are resistant to antiepileptic drugs and are controlled within an hour by 50-100 mg pyridoxin given intravenously. A maintenance dose of 5-10 mg/kg/day of oral pyridoxin is usually sufficient to control the seizures.