Inherited pediatric metabolic epilepsies

Abstract

Introduction: Inherited metabolic epilepsies are rare disorders that in aggregate represent significant morbidity. Emphasis is given here to entities in which early recognition and treatment are crucial.

Methodology: Review based on Literature Search (PubMed: Inherited metabolic epilepsies), Clinical Experience, Expert Opinion.

Results: Biopterin synthesis/recycling disorders can be misdiagnosed as atypical phenylketonuria. Cerebral folate deficiency, treatable with folinic acid, is associated with decreased CSF 5-methyltetrahydrofolate. Seizures may be the sole manifestation of biotinidase deficiency. Serine biosynthesis disorders are treatable with serine and glycine but otherwise result in microcephaly and epilepsy. Creatine synthesis disorders are amenable to creatine supplementation and other dietary modalities. A neonate presenting with seizures and diabetes may have a potassium channelopathy, DEND, responsive to oral hypoglycemics. Congenital hyperinsulinism with hyperammonemia (HI/HA) is associated with generalized epilepsy and treated with diazoxide, protein restriction, and antiepileptics. Glucose transporter-1 deficiency has an enlarging phenotype and is treatable with the ketogenic diet. Pyridoxine dependency is associated with antiquitin deficiency and is allelic to folinic acid dependency; PNPO (pyridoxamine 5′-phosphate oxidase) deficiency requires pyridoxal-5′-phosphate therapy. Urea cycle disorders precipitate severe neonatal hyperammonemia and are controlled with dialysis, protein-restriction, and nitrogen-scavenging drugs. Hyperekplexia, an epilepsy mimic involving glycine receptors or transporters, is manageable with benzodiazepine.

Expert opinion: Diagnostic and therapeutic recommendations are presented for these challenging conditions having potential catastrophic consequences but inherent treatability.

Keywords::

• genetic–metabolic
• infantile
• metabolic epilepsy
• neurotransmitter disease
• spasms

Notes

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