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Washington University Experience | METABOLIC | Menkes disease | 2A0 Case 2 History
Case 2 History ---- The patient was an 8 month old boy who had undergone extensive medical testing for a complex seizure disorder and neurodegenerative disease of unknown etiology. At birth he was noted to have microcephaly, scoliosis, and joint contractures. He began to have seizures at two weeks of age which were frequently intractable and occurred many times per hour, were characterized by facial grimacing, right greater than left arm clonic activity, and apnea with desaturation. Seizures were resistant to multiple anticonvulsants. Extensive evaluation for genetic and metabolic causes of his seizures was performed, including karyotyping, genetic studies for mitochondrial mutations, Angelman’s and Prader-Willi syndromes, serum and urine amino and organic acids, ammonia, very long-chain fatty acids, pipecolic acids, urine oligosaccharides and mucopolysaccharides, carnitine levels, acylcarnitine profile, CSF lactate, transferrin electrophoresis, biotinidase, and CSF neurotransmitter metabolites, all of which were unremarkable. Measurement of copper levels and ceruloplasmin were unfortunately not performed. The patient had normal appearing hair but it was not examined microscopically. Mitochondrial stains of a non-diagnostic muscle biopsy failed to show pathology. A conjunctival biopsy performed was normal. A skin biopsy was done at the same time, but the fibroblasts did not grow adequately for further testing. His last physical examination showed a microcephalic male without dysmorphic features. His reflexes were 3+ throughout. The patient was last hospitalized with increased seizure activity and apneic spells associated with periods of cyanosis and lowering of his oxygen saturation. The patient began to have problems with abdominal distention and had difficulty breathing and expired.
The weight of the fixed brain is 310 gm (normal 8 mo old unfixed brain weight is ~700 gm). Coronal sections of the cerebral hemispheres revealed an unremarkable cortical ribbon in most sites; however, both hippocampi were shrunken. The underlying white matter appears atrophic and is firm to palpation. The lateral and third ventricles are mildly dilated with blunting of lateral angles and a thinned (1 mm) corpus callosum consistent with loss of white matter and neurons. Radial sections of the cerebellum show well-formed foliar structures; however, both the vermis and hemispheres were small, white and firm to touch, consistent with extensive gliosis.
