Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome.
OBJECTIVE
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).


METHODS
Treatment with dietary cholesterol in patients with SLOS in a case series study.


METHODS
All biochemical analyses were performed in one laboratory. The clinical follow-up was carried out by one of the authors (LS), a paediatric neurologist.


METHODS
Seven patients with biochemically verified SLOS have been diagnosed in Sweden and all of them are included in the study.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000627:therapeutic use; D002784:Cholesterol / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood / Q000627:therapeutic use; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003684:Dehydrocholesterols / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D010787:Photosensitivity Disorders / Q000517:prevention & control; D011115:Polyneuropathies / Q000517:prevention & control; D012737:Sex Factors; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D015854:Up-Regulation
D002756:Cholagogues and Choleretics; D002791:Cholesterol, Dietary; D003684:Dehydrocholesterols; D013656:Taurocholic Acid; C001521:lathosterol; D002784:Cholesterol