Cerebrotendinous xanthomatosis, sitosterolemia, Smith-Lemli-Opitz syndrome and the seminal contributions of Gerald Salen, MD (1935-2020).

Cerebrotendinous xanthomatosis (CTX), sitosterolemia, and Smith-Lemli Opitz syndrome (SLOS) are rare inborn errors of metabolism. The diagnoses of CTX and sitosterolemia are often delayed for many years because of lack of physician awareness, often resulting in significant and unnecessary progression of disease. CTX may present with chronic diarrhea, juvenile onset cataracts, strikingly large xanthomas, and neurologic disease in the setting of a normal serum cholesterol, but markedly elevated serum or plasma cholestanol levels. These patients have a defect in producing the bile acid chenodoxycholate, and oral chenodeoxycholate therapy is essential for these patients in order to prevent neurologic complications. Sitosterolemia can present with xanthomas, anemia, thrombocytopenia, splenomegaly, very premature heart disease, and serum cholesterol levels that may be normal or elevated, along with marked elevations of plasma β-sitosterol. These patients have a defect causing overabsorption of β-sitosterol, and the treatment of choice is oral ezetimibe. SLOS presents with growth delay, intellectual disability, multiple structural anomalies, and low serum cholesterol levels, and the defect is reduced cholesterol production. Treatment consists of dietary cholesterol supplementation and oral bile acid therapy which raises serum cholesterol levels and may improve symptoms. The metabolic and genetic defects in these disorders have been defined. There is no one in our field that has contributed more to the diagnosis and treatment of these disorders than Gerald Salen, MD, who died in late 2020 at 85 years of age. He will be greatly missed by his family, friends, and colleagues from around the world.
Competing Interests: Declarations of Competing Interest None of the authors has any conflicts of interest at the present. Drs. Schaefer, Duell and Steiner have served as consultants for Retrophin, now known as Travere Therapeutics, San Diego, CA, in the past, but not in the last 12 months. Dr. Duell has institutional grants and support from Travere Therapeutics. This company manufactures and distributes chenodeoxycholic acid. Dr. Schaefer is an employee of Boston Heart Diagnostics, a clinical diagnostic laboratory that provides sterol testing. Dr. Steiner is an employee of PreventionGenetics, a laboratory that offers commercial genetic testing for these and other other disocorders; he received an honorarium for development and presentation of educational content for Medscape.
(Copyright © 2021. Published by Elsevier Inc.)