Rossi Massimiliano, D'Armiento Maria, Parisi Ida, Ferrari Paola, Hall Christine M, Cervasio Mariarosaria, Rivasi Francesco, Balli Fiorella, Vecchione Raffaella, Corso Gaetano, Andria Generoso, Parenti Giancarlo
Dipartimento di Pediatria, Federico II University, Naples, Italy, and Department of Radiology, Great Ormond Street Hospital for Children, London, UK.
Am J Med Genet A. 2007 Oct 15;143A(20):2371-81. doi: 10.1002/ajmg.a.31929.
Lathosterolosis (LS) is a defect of cholesterol biosynthesis due to the deficiency of the enzyme sterol-C5-desaturase. Only two patients have been described to date, both presenting with multiple malformations, mental retardation, and liver involvement. In addition in one of them pathological examination revealed mucolipidosis-like inclusions on optic microscopy analysis, and peculiar lysosomal lamellar bodies on electron microscopy analysis. This study is focused on a better characterization of the clinical phenotype of LS. We describe a further case in a fetus, sibling of the first patient reported, presenting with neural tube defect, craniofacial and limb anomalies, and prenatal liver involvement. The fetal phenotype suggests the possible occurrence of significant intrafamilial variability in LS, and expands the phenotypic spectrum of the disease. Histological examination of autopsy samples from the fetus and skin fibroblasts from the living sibling suggested that the mucolipidosis-like picture previously reported is not a constant feature of LS, being possibly associated with the most severe biochemical defects, but confirmed the ultrastructural finding of lamellar inclusions. The LS phenotype appears to be characterized by the distinctive association of a recognizable pattern of congenital anomalies, involving axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage. This condition partially overlaps with other defects of sterol metabolism, suggesting intriguing pathogenic links among these conditions.
羊毛甾醇病（LS）是一种由于甾醇-C5-去饱和酶缺乏导致的胆固醇生物合成缺陷。迄今为止仅报道了两例患者，均表现出多种畸形、智力发育迟缓以及肝脏受累。此外，其中一例患者的病理检查在光学显微镜分析中显示出类黏脂贮积症样包涵体，在电子显微镜分析中显示出特殊的溶酶体层状小体。本研究聚焦于对羊毛甾醇病临床表型的更好特征描述。我们报道了首例患者的同胞胎儿中的另一病例，该胎儿表现出神经管缺陷、颅面和肢体异常以及产前肝脏受累。胎儿的表型提示羊毛甾醇病可能存在显著的家族内变异性，并扩展了该疾病表型谱。对该胎儿尸检样本和存活同胞的皮肤成纤维细胞进行组织学检查表明，先前报道的类黏脂贮积症样表现并非羊毛甾醇病的恒定特征，可能与最严重的生化缺陷相关，但证实了层状包涵体的超微结构发现。羊毛甾醇病的表型似乎具有以下特征：涉及中轴和附属骨骼、肝脏、中枢神经和泌尿生殖系统的可识别先天性异常模式与溶酶体贮积症独特相关。这种情况与其他甾醇代谢缺陷部分重叠，提示这些病症之间存在有趣的致病联系。
