How we discovered a rare case of my rare disease

I’m not sure which surprised me more — that my 75-year-old mother was open to the obnoxious process of spitting into a saliva sample for a second time, or that my dad might have the Fabry mutation that three of my children and I share.

We recently learned about this disease’s genetics at our initial visit with Dr. Raphael Schiffmann. While diagnosing my boys’ Fabry disease, he asked about my parents and made the argument that my mother was most likely the carrier of the mutation, which is on the X chromosome. Thus, she likely passed it on, unless it developed de novo in me. That was logical because if my dad, 76, had lived with Fabry disease, he wouldn’t have enjoyed the health he’s had.

Dr. Schiffmann, a fabulously informed physician, was tracking our family’s genetic testing. We messaged back and forth about the mutation my sons shared, which was identified for the first time and registered in the Fabry database. After the same mutation showed up in my genes (and in my daughter’s), testing my parents became necessary to determine whether I’d inherited it. If so, that would necessitate further tests of my family of origin.

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I come from a family of seven children, and I cringed knowing that if my mom tested positive for the mutation, then each of my siblings would have a 50% chance of having the disease. The number of affected loved ones could be disturbingly high since my mother has 29 grandchildren! So I begged God that everyone would be spared and that the mutation would’ve started with me.

My mom’s first results were negative for Fabry. Still, she volunteered to do a second genetic test through a different company. The second result was also negative.

After that, we tested my dad. When his results came in, I got a phone call from Dr. Schiffmann, who wanted to tell me himself because the news was unexpected. My dad had the mutation, but his was a germline mosaic pattern, which meant his body still produced alpha-galactosidase A, which is deficient in Fabry. That’s why he lived without any symptoms of the disease.

Even Dr. Schiffmann, an authority on the history and causes of Fabry disease, was baffled. He told me he knew of only one other case of a man with a similar mosaicism where that man’s daughters inherited his mutation.

My heart sank. I have two sisters whom I love dearly, and each has a big family. It broke my heart to think that Sarah, Mary, and their kids were now facing the storm that was raging in my own home. Thankfully, my four brothers were off the hook (because men with Fabry do not pass the mutation to male offspring), but now we waited with bated breath for the genetic test results for Sarah and Mary.

Those results were nothing short of miraculous. Neither of my sisters has a Fabry mutation. There was no need for further testing because not a single person in my family of origin was affected by it but me.

Our Fabry inheritance diagram is quite rare. In every case I’ve read about, a man with a Fabry mutation automatically passes it on to each and every female offspring. The anomaly, that my dad only passed his mutation to me, was an answer to the cry of my heart, though I would never have imagined it possible. After months of waiting, hoping, and praying with folded hands and twisted stomach, finally the crooked lines had brought us straight to a huge relief.

So even within the rare disease world, sometimes the impossible happens and we find results that are completely unexpected. I guess the unwritten rule of this rare journey is that anything can happen, so here’s hoping for the best.

Note: Fabry Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Fabry Disease News or its parent company, Bionews, and are intended to spark discussion about issues pertaining to Fabry disease.