Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism
Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism
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DOI：
10.1002/(sici)1096-8628(19970131)68:3
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发表时间：
1997-01-31
期刊：
影响因子：
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通讯作者：
Kelley, RI
中科院分区：
文献类型：
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作者：
Cunniff, C;Kratz, LE;Kelley, RI
RSH/Smith-Lemli-Opitz(RSH/SLO)综合征是一种常染色体隐性遗传畸形综合征，最近发现与胆固醇生物合成严重不足以及血浆和组织中7-脱氢胆固醇(7-DHC)水平显著升高有关，7-DHC是Kandutsch-Russell生物合成途径中胆固醇的直接前体。由于这些生化异常允许重新评估RSH/SLO的生化标准，而不是较不特异的物理标准，我们在这里回顾了我们的第一批80例7-DHC水平异常升高的患者的临床和生化特征。研究人群包括68名指标性患者和另外12名亲属，通过定量测定血浆、羊水或培养的成纤维细胞、淋巴母细胞或羊水中的7-DHC和胆固醇来确定。在其他临床症状中，当重新定义生化时，我们发现RSH/SLO的临床表达范围比以前认识的更广泛。这些新发现的不典型的RSH/SLO患者包括几个除了脚趾并指外没有其他畸形的患者，另一个极端是死于宫内的坦率的全前脑或多发性内脏异常患者。脚趾2、3并指畸形是最常见的畸形，在80例患者中除1例外，其余均有发生。最能预测临床严重程度的生化指标是血浆胆固醇水平，随着临床严重程度的增加而降低。然而，至少10%的患者，包括一名新生儿，在诊断时胆固醇水平正常，如果没有7-DHC的具体定量，就会被漏掉。不出所料，几名临床诊断为RSH/SLO的患者被发现所有血浆固醇水平正常，培养细胞胆固醇生物合成明显正常。我们的生化鉴定患者的异常频率与以前报告的临床系列相似数据的比较表明，文献中高达25%的RSH/SLO报告可能描述了除RSH/SLO伴7-DHC-血症之外的其他遗传疾病。(C)1997年Wiley-Liss，Inc.
RSH/Smith-Lemli-Opitz (RSH/SLO) syndrome is an autosomal recessive malformation syndrome recently shown to be associated with a severe deficiency of cholesterol biosynthesis and markedly elevated plasma and tissue levels of 7-dehydrocholesterol (7-DHC), the immediate precursor of cholesterol in the Kandutsch-Russell biosynthetic pathway. Because these biochemical abnormalities permit a reassessment of RSH/SLO on biochemical criteria rather than less specific physical criteria, we review here the clinical and biochemical characteristics of our first 80 patients with abnormally increased levels of 7-DHC. The study population included 68 index patients and 12 additional relatives identified by quantification of 7-DHC and cholesterol in plasma, amniotic fluid, or cultured fibroblasts, lymphoblasts, or amniocytes. As demonstrated in other clinical syndromes when redefined biochemically, we have found a wider range of clinical expression of RSH/SLO than previously recognized. These newly recognized atypical RSH/SLO patients included several with no malformations other than syndactyly of the toes and, at the other extreme, patients with frank holoprosencephaly or multiple visceral anomalies who died in utero. Syndactyly of toes 2 and 3 was the most common malformation, occurring in all but one of 80 patients. The best biochemical predictor of clinical severity was the plasma cholesterol level, which decreased with increasing clinical severity. However, at least 10% of patients, including one newborn infant, had normal cholesterol levels at the time of diagnosis and would have been missed without specific quantification of 7-DHC. Not unexpectedly, several patients carrying a clinical diagnosis of RSH/SLO were found to have normal levels of all plasma sterols and apparently normal cholesterol biosynthesis in cultured cells. A comparison of the frequency of anomalies in our biochemically identified patients with similar data from previously reported clinical series suggests that up to 25% of reports of RSH/SLO in the literature may describe genetic conditions other than RSH/SLO with 7-DHC-emia. (C) 1997 Wiley-Liss, Inc.