A classic variant of Fabry disease in a family with the M296I late-onset variant
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CASE REPORT
A classic variant of Fabry disease in a family with the M296I late‑onset variant Shuma Hirashio1 · Reiko Kagawa2 · Go Tajima3 · Takao Masaki1 Received: 13 April 2020 / Accepted: 28 August 2020 © Japanese Society of Nephrology 2020
Abstract 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. Keywords Fabry disease · M296I mutation · Classic variant · Late-onset variant · Genotype · Phenotype
Introduction
* Takao Masaki masakit@hiroshima‑u.ac.jp Shuma Hirashio [email protected] Reiko Kagawa [email protected]‑net.ne.jp Go Tajima tajima‑[email protected] 1
Department of Nephrology, Hiroshima University Hospital, Hiroshima, 1‑2‑3 Kasumi, Hiroshima 734‑8551, Japan
2
Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Hiroshima, 1‑2‑3 Kasumi, 734‑8551, Japan
3
Division of Neonatal Screening, Research Institute, National Center for Child Health and Development, 2‑10‑1 Okura, Setagaya‑ku, Tokyo 157‑8535, Japan
Fabry disease is a disease of glycosphingolipid metabolism with X-linked recessive inheritance caused by deficiency or reduced activity of α-galactosidase A (α-gal A). This disease constitutes a lysosomal storage disorder caused by mutations in the α-gal A-encoding gene on the X chromosome (Xq22.1) [1]. Storage of glycosphingolipids within the lysosomes of various organs results in fatal complications, such as progressive hypertrophic cardiomyopathy, severe heart failure, end-stage
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