Elevated serum cholestanol is a marker for cerebrotendinous xanthomatosis, a leukodystrophy characterized by lipid accumulation within the tendon sheaths and lungs (xanthomas), cataracts, progressive ataxia and dementia. Treatment with chenodeoxycholic acid can substantially improve dementia and ataxia. Smith-Lemli-Opitz causes microcephaly, dysmorphic features, and global developmental delay, and is caused by mutations in 7-dehydrocholesterol reductase, leading to elevated 7-dehydrocholesterol and low total cholesterol. Treatments under investigation for this disorder include cholesterol supplementation and statins. Zellweger disease is a peroxisomal disorder, with abnormal very long chain fatty acids accumulation, while Niemann-Pick, type C causes progressive extrapyramidal symptoms, vertical supranuclear gaze palsy and psychomotor regression, with biochemical testing showing impaired cholesterol esterification. Farber disease (ceramidase deficiency) is a multisystem disorder due to mutations in acid ceramidase (ASAH1), leading to sphingolipid accumulation in many tissues, including the central nervous system, joints, liver, and vocal cords.
References:
Ropper AH and Samuels MA. “Inherited Metabolic Diseases of the Nervous System.” in Adams and Victor’s Principles of Neurology, 9th Edition. New York: McGraw-Hill Comp., Inc., 2009
