Cases of Fabry Disease in Which Pathogenic Variants Are Not Detected in Parent-Child Pairs.

A 15-year-old male has been experiencing fever, limb pain during exercise, and reduced sweating since childhood. During an investigation into his fever, a family history of Fabry disease was discovered, prompting a referral to our department. He was diagnosed with Fabry disease based on decreased alpha-galactosidase A (α-Gal A) activity. Concurrently, his mother was found to have experienced limb pain during fevers since childhood, and she was also diagnosed with Fabry disease based on decreased α-Gal A activity. In the genetic analysis of both individuals, the IVS1+17A>G GLA variant was identified. This variant is considered benign and not classified as a pathogenic variant. Enzyme replacement therapy has been effective in improving clinical symptoms. His sister, who has not been diagnosed with Fabry disease due to normal clinical symptoms and α-GAL A activity, also had the same variant. Among the various GLA variants, many are classified as benign rather than pathogenic. In the present cases, the possibility of other factors that cannot be identified by genetic analysis is suggested, making this case significant and worth reporting.