Choy F Y
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
J Med Genet. 1988 May;25(5):322-5. doi: 10.1136/jmg.25.5.322.
Glucocerebroside beta-glucosidase (glucocerebrosidase) activity was determined from peripheral blood lymphocytes and cultured skin fibroblasts of eight full sibs in a French-Canadian family at risk for Gaucher disease, an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. The diagnosis of type 1, non-neuronopathic Gaucher disease was made in all of the five affected sibs on the basis of deficient (7.5 to 15.5% of control mean) glucocerebrosidase activity and absence of neurological involvement. Normal levels of enzyme activity were found in two of the three asymptomatic sibs. The third asymptomatic sib had an intermediate level (about 50% of control mean) of fibroblast and lymphocyte glucocerebrosidase activity, indicating that he is a carrier. Considerable clinical heterogeneity was noted among the five affected sibs. One patient is mildly affected and so far has not developed any orthopaedic complications associated with Gaucher disease. His haematological complications were also reversed after splenectomy 24 years ago. In contrast to this mild presentation, the patient's splenectomised sister has been very anaemic and thrombocytopenic. There have been severe orthopaedic complications associated with Gaucher disease, including vertebral compression, avascular necrosis, and pathological fracture of the long bones. The clinical picture of the other three affected sibs appeared to vary between the two extremes. Although the asymptomatic parents of the patients died many years ago, their heterozygous status with respect to Gaucher disease can be deduced by the presence of Gaucher homozygotes, normal homozygotes, and one heterozygote among their eight offspring. Present findings suggest that the clinical variability of type 1 Gaucher disease may be attributed to variable expressions of the same Gaucher mutant alleles, in addition to the presence of multiple mutant alleles that are widely disseminated in the population.
在一个有戈谢病风险的法裔加拿大家庭中，对八名全同胞的外周血淋巴细胞和培养的皮肤成纤维细胞进行了葡糖脑苷脂β - 葡萄糖苷酶（葡糖脑苷酶）活性测定。戈谢病是一种常染色体隐性鞘脂贮积病，由葡糖脑苷酶活性缺乏引起。根据葡糖脑苷酶活性不足（为对照平均值的7.5%至15.5%）且无神经受累情况，对五名受影响的同胞作出了1型非神经病变性戈谢病的诊断。在三名无症状同胞中，有两名酶活性水平正常。第三名无症状同胞的成纤维细胞和淋巴细胞葡糖脑苷酶活性处于中间水平（约为对照平均值的50%），表明他是携带者。在五名受影响的同胞中观察到了相当大的临床异质性。一名患者症状较轻，迄今为止尚未出现与戈谢病相关的任何骨科并发症。他的血液学并发症在24年前脾切除术后也得到了缓解。与这种轻微表现形成对比的是，该患者接受脾切除的姐姐一直严重贫血和血小板减少。出现了与戈谢病相关的严重骨科并发症，包括椎体压缩、缺血性坏死和长骨病理性骨折。其他三名受影响同胞的临床表现似乎介于这两个极端之间。尽管患者无症状的父母多年前已去世，但根据他们的八个后代中有戈谢病纯合子、正常纯合子和一名杂合子，可以推断出他们在戈谢病方面的杂合状态。目前的研究结果表明，1型戈谢病的临床变异性可能归因于相同戈谢突变等位基因的可变表达，此外还存在在人群中广泛传播的多个突变等位基因。
