Familial lipodystrophy associated with neurodegeneration and congenital cataracts

The lipodystrophies are characterized by loss of body fat and metabolic disturbances, but the CNS is seldom affected.

An investigation of a family with partial lipodystrophy and neurologic abnormalities included lipid analysis, dual-energy x-ray absorbtiometry (DEXA) for adiposity, insulin resistance, karyotype and other genetic analyses, peroxisomal function, glycosylation pattern of transferrin and thyroglobulin, and muscle biopsy.

The propositus, a 28-year-old woman with congenital partial lipodystrophy and cataracts, presented with a spastic-ataxic gait and lower extremity paresthesiae at age 18. Laboratory investigation revealed a type V hyperlipidemia pattern, insulin resistance, and high alpha-tocopherol levels. A similar syndrome in other family members suggested an autosomal dominant pattern of inheritance.

The progressive neurologic degenerative condition associated with this autosomal dominant, partial lipodystrophy may be misdiagnosed as MS or spinocerebellar degeneration. Search for a few relevant candidate genes was unrevealing. A genome-wide search to determine the molecular etiology can be undertaken if other similar cases are identified.