…But you didn’t order fries and you certainly don’t want the combo meal!
I recently read about Kelly du Plessis, a Mom in South Africa whose 6 year old son has been diagnosed with both Pompe disease (a.k.a Acid maltase deficiency (AMD)), a lysomal storage disease, and Prkage2 Syndrome, a heart condition.
She has been told that there are only 12 other cases in the world in which kids have been diagnosed with both of these genetic issues. She would love to meet one. We can assume that there are actually many more such cases because so many people are undiagnosed, misdiagnosed, or unreported.
Because there has not been a long standing uniform coding system for rare and ultra-rare diseases, many have not been recorded– even if they have been recognized– in a way in which others can easily find them. The ICD 10 coding (and perhaps next year the ICD 11) attempts to capture more rare conditions uniformly.
But why, and how do two or more rare conditions occur in the same individual?
The short answer:
- Sometimes the rare conditions are related to the same string of gene deletions
- One mutation can cause two different conditions
- Other times, it is just bad luck to have two different genes with mutated alleles
There are “contiguous gene syndromes” caused by deletions of a whole string of genes, causing multiple conditions at the same time. Those conditions together become known as the contiguous gene. Contiguous deletions require they be relatively close to each other on the same chromosome. Pompe and Prkage2 Syndrome, are on completely separate chromosomes.
In addition, there are also changes in some genes that cause one condition in an autosomal dominant (AD) manner, meaning only one copy of a mutated allele is sufficient to cause clinical symptoms, thus a child only need inherit one mutated allele from one of his parents. There is another in an autosomal recessive manner, meaning that an individual must inherit a mutated allele from both parents, e.g. BRCA2 causing an increased risk for breast cancer AD inheritance, and Fanconi Anemia in an autosomal recessive pattern. Someone with two mutated alleles not only has an increased risk for breast cancer, they also have an increased risk for fanconi anemia.
Glycogen storage disease of the heart, caused by a mutation in the gene Prkag2, is autosomal dominant. Thus, an individual with only one mutated allele will have symptoms. An affected individual has a 50% chance to pass on their mutated allele to a child, who will have the condition as well. Pompe disease, on the other hand, is autosomal recessive. In order to be affected, a child must inherit one mutated allele from each parent.
For Kelly’s son, it makes no difference. No matter how statistically rare it is to have two rare diseases, for him and his family it is 100%.
