The age of onset of seizures is another important element in arriving at a diagnosis.

Frequent seizures as early as the neonatal period may result from:

• cerebral malformations such as lissencephaly
• hypoglycemia
• hypocalcemia
• intracranial hemorrhage or infection
• drug withdrawal
• hereditary metabolic diseases (Table: Age of Onset)

Intractable seizures in the period of early infancy can result from:

• Alpers’ disease
• glucose transporter protein deficiency5
• Haltia-Santavuori variant of neuronal ceroid-lipofuscinosis (CLN1)
• Krabbe’s disease (by age 6 months)
• classic Tay-Sachs disease (by age 1 year)

Biotinidase deficiency and, occasionally, vitamin B6 dependency may present at this time and not in the neonatal period.

The progressive myoclonic epilepsies are associated with clinical onset in later childhood and adolescence:

• Unverricht-Lundborg disease (Baltic myoclonus) is an autosomal recessive neurodegeneration in which myoclonic jerks and generalized tonic-clonic seizures are associated with progressive mental deterioration and ataxia. This disease has been identified with alterations in the cystatin B (Stefin B) gene.



• Lafora’s disease, another autosomal recessive condition exhibiting myoclonus and dementia, is distinguished by periodic acid–Schiff–positive intracellular inclusion bodies in neurons and other tissues. The majority of patients have mutations in the EPM2 gene on chromosome 6q23-q25.6



• Other familial forms of juvenile myoclonic epilepsy have been linked to chromosomes 6p21.2-p11 and 15q14.



• juvenile neuronal ceroid-lipofuscinosis (CLN3)



• type 3 Gaucher’s disease



• sialidosis type I

Later, in young adults, one may encounter seizures as a sign of mitochondrial disease such as MERRF (myoclonic epilepsy with ragged red fibers). MERRF is a maternally inherited encephalomyopathy, in most cases due to an A8344G transition in the tRNA Lys gene of mitochondrial DNA.

Adapted from: Kolodny, EH. Metabolic and genetic disorders. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;17–22.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.