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Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol‐synthesis defect Smith–Lemli–Opitz syndrome
Author(s) -
Starck L.,
LövgrenSandblom A.,
Björkhem I.
Publication year - 2002
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1046/j.1365-2796.2002.01037.x
Subject(s) - smith–lemli–opitz syndrome , lathosterol , cholesterol , medicine , hypocholesterolemia , sterol , endocrinology , reductase , bile acid , gastroenterology , enzyme , biochemistry , biology , 7 dehydrocholesterol reductase , campesterol
Objectives. To investigate if exogenous cholesterol affects sterol turnover in the cholesterol‐synthesis defect Smith–Lemli–Opitz syndrome (SLOS) and if clinical effects justify long‐time supplementation. The SLOS is caused by a deficiency of the enzyme 7‐dehydrocholesterol‐7‐reductase with markedly reduced cholesterol levels and greatly increased levels of 7‐dehydrocholesterol (7‐DHC). Design. Treatment with dietary cholesterol in patients with SLOS in a case series study. Setting. All biochemical analyses were performed in one laboratory. The clinical follow‐up was carried out by one of the authors (LS), a paediatric neurologist. Subjects. Seven patients with biochemically verified SLOS have been diagnosed in Sweden and all of them are included in the study. Interventions. Six patients were treated for 0.5–6 years orally with cholesterol and the bile acid taurocholate and one patient was supplemented with cholesterol only. Main outcome measures. In addition to cholesterol, 7‐ and 8‐DHC, lathosterol was used as a marker of endogenous cholesterol synthesis and the patients were followed clinically. Nerve conduction velocities (NCV) were measured before treatment in all patients and a UVA‐light test was performed in one of them. Results. Lathosterol was initially increased by cholesterol supply in subjects with very low cholesterol levels with subsequent rise of 7‐ and 8‐DHC. Photosensitivity clinically improved in all, verified by UVA‐light testing in one. Progressive polyneuropathy improved, whilst stationary forms did not. Conclusion. Dietary cholesterol can up‐regulate sterol turnover in severely affected patients. Although some specific features are treatable and verifiable by objective methods, data supporting life‐long treatment dietary cholesterol in all SLO patients are still lacking.