Treatment of Smith–Lemli–Opitz syndrome and other sterol disorders

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic condition with a broad phenotype that results from deficiency of the final enzyme of the cholesterol synthesis pathway. This defect causes low or low-normal plasma cholesterol levels and increased 7- and 8-dehydrocholesterol (DHC) levels. Many therapies for SLOS and other disorders of sterol metabolism have been proposed, and a few of them have been undertaken in selected patients, but robust prospective clinical trials with validated outcome measures are lacking. We review the current literature and expert opinion on treatments for SLOS and other selected sterol disorders, including dietary cholesterol therapy, statin treatment, bile acid supplementation, medical therapies and surgical interventions, as well as directions for future therapies and treatment research.

Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

“…Because the defect in DHCR7 leads to low plasma cholesterol levels and elevated 7-and 8-dehydrocholesterol levels, current treatment standards include dietary cholesterol supplementation with statin therapy [123]. There are also currently studies examining the benefits of antioxidants in the treatment of SLOS (E. Elias, personal communication).…”

A koleszterin-bioszintézis veleszületett zavara: a Smith–Lemli–Opitz-szindróma

“…Ugyan a vér-agy gát integritásá-nak sérüléséhez vezethet SLO-szindrómában a Sonic hedgehog útvonal nem megfelelő működése, azonban a már kialakult központi idegrendszeri eltéréseket a bejutott koleszterin nem tudja befolyásolni [40].…”

“…A kezelés klinikai hatékonyságával számos tanulmány foglalkozott, amelyek nem objektív, standardizált mérő-számok alapján határozták meg a klinikai hatékonyságot [40].…”

“…Ismeretes a statinok szisztémás antioxidáns hatása is. Jelenleg kutatási célú vizsgálatokon kívül a statinok rutinszerű alkalmazása SLO-szindrómában nem ajánlott [40].…”

Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome

“…To date, routine therapy has been cholesterol supplementation in SLOS; while combined cholesterol-simvastatin therapy (9,10) or cholesterol-antioxidant treatment might also be effective in SLOS patients (11). However, as it was recently reviewed, simvastatin is not recommended for SLOS treatment due to its potential side effects (12). High oxidizability of 7DHC has been reported to enhance endogenous oxidative stress in cell and animal models of SLOS (13) and in several human studies (14).…”