Pyridoxine-Dependent Seizures Associated With Hypophosphatasia in a Newborn

Abstract

Pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. Pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. Pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome.

Hypophosphatasia Presenting with Pyridoxine-Responsive Seizures, Hypercalcemia, and Pseudotumor Cerebri: Case Report

“…Pyridoxine-responsive seizures have been reported in association with HPP, and in fact, they are considered to be an indicator of disease severity (8,9,10,11). Several specific mutations have been suggested to be responsible (8,9,10,11,12).…”

“…Several specific mutations have been suggested to be responsible (8,9,10,11,12). A very similar case has been reported by Baumgartner-Sigl et al previously (8).…”

Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene

“…The mechanism of pyridoxine-responsive seizures in HPP is explained by defective metabolism of pyridoxal 5-phosphate (PLP), which is the phosphorylated form of pyridoxine. PLP, one of the natural substrates of ALP, is the active compound by which pyridoxine mediates essential enzyme activity; PLP deficiency in the central nervous system may reduce seizure threshold by reducing neurotransmitter (GABA) synthesis (11,12,13,14,15,16). …”

TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism

“…Beyond their often more prominently manifesting mineralization phenotype, HPP patients show neurological symptoms, including epileptic seizures, depression, anxiety, and sleeping disorders (in an increased prevalence compared to the general U.S. population) [74]. Epileptic seizures occur in severely affected children but not in adult patients with milder onset [74][75][76]. Those seizures are often pyridoxine-dependent and have been linked to TNAP s biochemical function to indirectly provide the brain with PLP, which is an important co-factor for central enzymes of the neurotransmitter metabolism in the central nervous system, e.g., glutamate decarboxylase (GAD) and aromatic L-amino acid decarboxylase (AADC) [75,77,78].…”