Filocamo Mirella, Mazzotti Raffaella, Stroppiano Marina, Grossi Serena, Dravet Charlotte, Guerrini Renzo
Laboratorio Diagnosi Pre-Postnatale Malattie Metaboliche, IRCCS G.Gaslini, Genoa, Italy.
Epilepsia. 2004 Sep;45(9):1154-7. doi: 10.1111/j.0013-9580.2004.15904.x.
Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase, is characterized by genotypic and phenotypic heterogeneity. We recently characterized the glucocerebrosidase alleles of a patient with an unusual clinical presentation of type 3 Gaucher disease.
Initial clinical manifestations appeared at age 11 years as visual seizures.
Subsequent progressive myoclonus and generalized seizures were consistent with an adolescent-onset form of progressive myoclonus epilepsy. However, a specific diagnosis was established only at age 16, because of the absence of hematologic abnormalities and a fairly moderate hepatomegaly. Bone marrow aspirate was slightly positive for Gaucher cells. Demonstration of reduced glucocerebrosidase in the fibroblasts confirmed the diagnosis. The child died at age 19 years. Postmortem sequencing of the glucocerebrosidase gene from cultured fibroblasts demonstrated a rare compound heterozygote for N188S/S107L.
This unusual presentation of Gaucher disease indicates that if clinical and neurophysiological findings in adolescents with initial visual seizures and myoclonus suggest a progressive disorder, enzymatic assay is mandatory, even in the absence of the classic neurologic and systemic signs of the disease. Early differential diagnosis from other forms of progressive myoclonus epilepsy with similar clinical presentation may help provide appropriate genetic counseling.
戈谢病是一种由于溶酶体酶葡萄糖脑苷脂酶遗传性缺乏引起的疾病，具有基因型和表型的异质性。我们最近对一名患有3型戈谢病不寻常临床表现患者的葡萄糖脑苷脂酶等位基因进行了特征分析。
最初的临床表现出现在11岁时，表现为视觉性癫痫发作。
随后出现的进行性肌阵挛和全身性癫痫发作与青少年起病型进行性肌阵挛癫痫相符。然而，由于没有血液学异常且肝肿大程度较轻，直到16岁才确诊。骨髓穿刺液中戈谢细胞呈弱阳性。成纤维细胞中葡萄糖脑苷脂酶活性降低证实了诊断。该患儿19岁时死亡。对培养的成纤维细胞中葡萄糖脑苷脂酶基因进行尸检测序，发现了一种罕见的N188S/S107L复合杂合子。
戈谢病的这种不寻常表现表明，如果患有初始视觉性癫痫发作和肌阵挛的青少年的临床和神经生理学检查结果提示为进行性疾病，即使没有该疾病的典型神经和全身体征，也必须进行酶学检测。早期与其他具有相似临床表现的进行性肌阵挛癫痫形式进行鉴别诊断，可能有助于提供适当的遗传咨询。
