Late-onset generalized disorder of peroxisomes

Peroxisomes are single-membrane-bound subcellular organelles found in almost all eukaryotic cells. There are more than 60 identified enzymes in peroxisomes. Functional peroxisomes are necessary for normal development, and deficiencies of peroxisome number, structure, or function produce severe disease. Peroxisomal disorders are usually diagnosed on the basis of clinical features and increased concentration of very-long-chain fatty acids (VLCFAs).

Peroxisomal disorders are classified into three groups based on biochemical and histologic criteria. ^[1] Group 1 disorders (e.g., Zellweger syndrome are particularly severe, characterized by defective peroxisome assembly and lacking all peroxisomal functions. Group 2 disorders (e.g., X-linked adrenoleukodystrophy [X-ALD]) have deficiencies of single peroxisomal enzymes and are usually less clinically severe than group 1 disorders. In group 3 disorders, multiple peroxisomal enzymes are defective, but peroxisomes are present as in group 2. We present an unusual case of a 32-year-old man having an atypical clinical course, plasma studies suggestive of a group 2 disorder, and the peroxisomal enzyme profile of group 1 or 3 disorders.

Case report.

This patient presented to the University of Michigan Neurology Clinic as a 32-year-old man with profound dementia and medically refractory epilepsy. His parents were first cousins. Of four siblings, one sister died at age 8 years with a neurologic disorder that included seizures from infancy and severe developmental delay. She never walked, talked, or sat unsupported. Our patient sat at 8 months, walked at 14 months, and talked in sentences at 2 years of age. The age at which cognitive delay became apparent is unknown. At 8 years, he developed generalized tonic-clonic seizures that became medically refractory. Also at age 8 years, he underwent developmental assessment for mental retardation. At that time, he ambulated well, played with his brothers, and performed activities of daily living. Severe hearing impairment …