Department of Nephrology, Hiroshima University Hospital, Hiroshima, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan.
Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Hiroshima, 1-2-3 Kasumi, 734-8551, Japan.
CEN Case Rep. 2021 Feb;10(1):106-110. doi: 10.1007/s13730-020-00527-0. Epub 2020 Sep 9.
Fabry disease is an X-linked recessive disease of glycosphingolipid metabolism caused by deficiency or reduced activity of α-galactosidase A. Fabry disease phenotypes are known to consist of a classic variant and a late-onset variant. In patients with Fabry disease, the phenotype is generally considered to be defined (at least partially) by the genotype. However, patients with the classic variant have been encountered in families with mutations that are expected to produce the late-onset variant. Here, we describe a 4-year-old boy with a classic variant of Fabry disease in a family with the M296I late-onset variant. The patient's grandfather, mother, and aunt experienced late-onset disease, characteristic of the M296I variant. Conversely, the patient experienced typical disease symptoms in childhood. He had symptoms of hypohidrosis and associated heat accumulation. He cried at night due to the occurrence of severe acroparaesthesia. This symptom became more pronounced in warmer climates. Although the patient's family had a late-onset variant mutation of Fabry disease, we determined that the patient's symptoms were similar to those of classic Fabry disease. Therefore, the patient began enzyme replacement therapy, which alleviated his symptoms. Notably, enzyme replacement therapy led to rapid improvement of the patient's subjective symptoms. Thus, we presumed that the patient's symptoms supported a diagnosis of classic Fabry disease. These findings suggest that childhood symptoms may occur in patients with Fabry disease, even in families with late-onset variant mutations. The genotype-phenotype correlation in Fabry disease remains controversial.
法布里病是一种 X 连锁隐性糖脂代谢疾病，由α-半乳糖苷酶 A 缺乏或活性降低引起。已知法布里病表型由经典变异型和迟发性变异型组成。在法布里病患者中，表型通常被认为至少部分由基因型定义。然而，已经在预期产生迟发性变异型的突变的家族中遇到了具有经典变异型的患者。在这里，我们描述了一个具有经典变异型法布里病的 4 岁男孩，他的家族存在 M296I 迟发性变异型突变。患者的祖父、母亲和阿姨都患有迟发性疾病，这是 M296I 变异型的特征。相反，患者在童年时就出现了典型的疾病症状。他有少汗和相关的热量积聚的症状。由于发生严重的肢端感觉异常，他在夜间哭泣。这种症状在气候较暖时更为明显。尽管患者的家族存在法布里病的迟发性变异型突变，但我们确定患者的症状与经典法布里病相似。因此，患者开始接受酶替代治疗，这缓解了他的症状。值得注意的是，酶替代治疗导致患者的主观症状迅速改善。因此，我们推测患者的症状支持经典法布里病的诊断。这些发现表明，即使在具有迟发性变异型突变的家族中，法布里病也可能在儿童期出现症状。法布里病的基因型-表型相关性仍存在争议。
