Metabolic and genetic disorders are a major diagnostic consideration whenever the physician is confronted with cognitive impairment, developmental disabilities, and epilepsy. At the onset of the disorder, rarely are the clinical signs so specific that the diagnosis is obvious. Even after some months and progression of the disease, the diagnosis often is still in doubt. A biochemical, molecular DNA, or chromosomal anomaly or cerebral malformation can remain hidden, to be discovered only after the appropriate tests are carried out.

The occurrence of seizures in a child with developmental delay can be an important clue to the presence of an inherited metabolic disease or other genetically determined disorder of the nervous system. As the actual cause may be occult, a systemic approach is needed in the investigation of these youngsters. Biochemical screening, electroencephalography, and brain magnetic resonance imaging (MRI) are essential. Additional studies are determined by the family history, age of onset, the presence or absence of any distinguishing physical features, and the nature of the neurologic findings.

In the management of any child with a developmental disability, the guiding principle should always be to uncover the primary etiology, which will determine available treatment options, prognosis, and opportunities for preventing a recurrence of the disease in future family members.

Treatment should be tailored to correcting metabolic error whenever possible. In many of the neurodegenerative disorders involving seizures, however, judicious use of anticonvulsants is the primary treatment modality. If a biochemical or DNA marker is available and the condition is serious enough to warrant prenatal diagnosis, the family should be informed about the availability of this option.

As hundreds of metabolic and genetic diseases can be associated with developmental disabilities and epilepsy,1,2 how can a clinician keep track of this field and know which tests are indicated in a particular case? The aim of these pages is to describe a useful approach to meet this challenge.