Boy with Fabry disease diagnosed with co-occurring blood disorder
Study: Fabry with congenital dyserythropoietic anemia not reported before
A 10-year-old boy diagnosed with Fabry disease was also found to have a rare blood disorder called congenital dyserythropoietic anemia (CDA) in a case researchers said was highly unusual.
In CDA, anemia, that is, a shortage of red blood cells that transport oxygen in the bloodstream, results in symptoms like fatigue, weakness, and pale skin.
“CDA … and [Fabry disease] co-occurring in the same patient is a very rare medical finding [that] has never been reported,” the researchers wrote. “This case … underscores the need for further investigation into potential genetic and [disease-causing] links between these seemingly disparate conditions.”
The case was described in “The unlikely combination: Anderson–Fabry disease and congenital dyserythropoietic anemia type II in a pediatric patient,” in Clinical Case Reports.
The boy was started on treatment with agalsidase alfa, an enzyme replacement therapy for Fabry, but no follow-up data regarding his treatment outcomes was provided.
Fabry disease is caused by mutations in the GLA gene, which provides instructions for producing the alpha-galactosidase A (alpha-Gal A) enzyme. The mutations typically affect the activity of alpha-Gal A and lead to fat molecules — mainly globotriaosylceramide (Gb3) and lyso-Gb3 — accumulating in several tissues and organs. Symptoms include pain, gastrointestinal issues, and skin rash, and may involve the kidneys, heart, and nervous system.
Diagnosed with two rare conditions
The boy was admitted to a pediatric clinic having had a pale appearance and recurrent infections in the previous months. A physical exam showed his vital signs were stable and he had normal growth, but an ultrasound revealed an enlarged spleen.
Laboratory work indicated low hemoglobin, the protein that carries oxygen in red blood cells, and high levels of total bilirubin, although direct bilirubin was in the normal range. Total bilirubin includes indirect bilirubin, the one that results from the breakdown of red blood cells, and direct bilirubin, an indicator of liver function.
The boy had ferritin levels that were just above the lower normal range. Ferritin is a protein that stores iron needed to make healthy red blood cells. The boy was treated with folic acid and iron supplements, which didn’t significantly increase his hemoglobin or reduce the levels of total bilirubin.
Whole genome sequencing, which allows for the sequencing of a person’s complete genetic information, revealed genetic mutations consistent with Fabry disease, which, together with lower than normal alpha-GalA activity confirmed the disease diagnosis.
The boy also had a mutation that led to a CDA type 2 diagnosis. This CDA type is the most common one and is marked by anemia, and liver and spleen enlargement. He was referred to a pediatric neurologist and started treatment with agalsidase alfa every two weeks. Agalsidase alfa is an enzyme replacement therapy, meaning it provides a working version of the alpha-Gal A enzyme to ease Fabry symptoms. The treatment is approved as Replagal in Europe and other countries, but not in the U.S.
No information about the result of treatment was provided by the researchers.
“The combined form of both entities of disorders isn’t widely known. Since both CDA and [Fabry disease] are rare genetic disorders, the likelihood of an individual having both conditions simultaneously is exceedingly low,” the researchers wrote. “To the best of our knowledge, it is the first case of [Fabry disease] and CDA type II, coexisting in a 10-year-old boy.”
About the Author
