Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome
Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome
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DOI：
10.1007/s00431-012-1925-z
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发表时间：
2013-05-01
影响因子：
3.6
通讯作者：
Balogh, Istvan
中科院分区：
文献类型：
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作者：
Olah, Anna V.;Szabo, Gabriella P.;Balogh, Istvan
Smith-Lemli-Opitz 综合征 (SLOS) 是一种伴有严重智力障碍的多发性先天性异常，是由 7-脱氢胆固醇还原酶活性降低引起的。根据临床症状、血清胆固醇、7-脱氢胆固醇和分子遗传学检测，15 名匈牙利患者被诊断为 SLOS。轻度 SLOS（n = 4，临床评分 < 20）诊断时的年龄为 0.5-18 岁，胆固醇为 2.37 +/- 0.8 mmol/L，7DHC 为 0.38 +/- 0.14 mmol/L。在典型SLOS组（n = 7，评分20-50）中，诊断时间较早（0.1-7岁）； t-胆固醇为1.47+/-0.7mmol/L，7DHC为0.53+/-0.20mmol/L。严重SLOS患者（n = 4，临床评分> 50）在新生儿时死亡，其t-胆固醇最低（0.66 +/- 0.27 mmol/L），7DHC为0.47 +/- 0.14 mmol/L。初始 t-胆固醇与临床严重程度的相关系数为 0.74，Cho/7DHC 与临床严重程度的相关系数为 0.669。轻度和重度 SLOS 的初始 t-胆固醇之间以及各组的 Cho/7DHC 比率之间存在统计学显着差异（p = 0.01）（p = 0.004）。在严重 SLOS 中，α-脂蛋白的百分比显着低于典型 (p = 0.003) 和轻度 SLOS (p = 0.004)。虽然补充胆固醇（n = 10）联合他汀类药物治疗（n = 9）期间血清白蛋白、总胆红素和止血参数仍保持在参考范围内，但50%的患者天冬氨酸转氨酶和丙氨酸转氨酶升高可能与肝功能的可逆性改变有关；因此，他汀类药物治疗被暂停。结论：预期寿命从根本上由初始t-胆固醇决定，但脱氢胆固醇和α-脂蛋白具有预后价值。肝毒性 DHC 的积累可能会抑制 α-脂蛋白的合成，从而减少胆固醇的反向转运。在他汀类药物治疗期间，我们建议监测血脂参数和肝功能。
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 alpha-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 alpha-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of alpha-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.