Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome.

UNLABELLED

Smith-Lemli-Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n = 4, clinical score <20) was 0.5-18 years, cholesterol was 2.37 ± 0.8 mmol/L, and 7DHC was 0.38 ± 0.14 mmol/L. In the group of typical SLOS (n = 7, score 20-50), the diagnosis was set up earlier (age of 0.1-7 years); t-cholesterol was 1.47 ± 0.7 mmol/L, and 7DHC was 0.53 ± 0.20 mmol/L. Patients with severe SLOS (n = 4, clinical score > 50) died as newborns and had the lowest t-cholesterol (0.66 ± 0.27 mmol/L), and 7DHC was 0.47 ± 0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p = 0.01), and between the Cho/7DHC ratios of groups (p = 0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p = 0.003) and mild SLOS (p = 0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n = 10) combined with statin therapy (n = 9), increase of aspartate aminotransferase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended.

CONCLUSION

life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.