In rare case, woman diagnosed with both Fabry and blood disorder
Study stresses need to consider rare diseases for unexplained symptoms
In what researchers say is the first reported case of its kind, a woman in China in her 60s was diagnosed with two co-occurring rare conditions: Fabry disease and myelodysplastic syndrome, known as MDS, a disorder in which a person’s bone marrow doesn’t make enough healthy blood cells.
The authors noted that several other family members showed signs of both diseases, with relatives — including the woman’s son — carrying the same Fabry-causing genetic mutation alongside low levels of platelets, the cell fragments that help with blood clotting.
“This case highlights the importance of considering rare diseases when faced with unexplained multisystem symptoms, particularly in patients with a family history,” the researchers wrote, also noting that a “mutation identified in this case is a novel … variant that has not been previously reported in the literature.”
While Fabry disease is rare, the researchers highlighted that “recent newborn screening studies suggest a potentially higher incidence of [Fabry], especially in atypical forms,” than may have been previously considered.
The woman’s case was described in a study titled “Fabry Disease Associated With Myelodysplastic Syndrome: Case Report,” which was published in the journal Clinical Case Reports.
In Fabry, mutations in the GLA gene reduce the production of the alpha-galactosidase A enzyme, known as alpha-Gal A, leading to the abnormal accumulation of fatty molecules, primarily globotriaosylceramide (Gb3) in cells. Over time, the accumulation of these substances in multiple organs disrupts normal function, leading to disease symptoms.
MDS is a group of disorders in which immature blood cells in the bone marrow fail to mature into healthy blood cells. Symptoms may include fatigue, shortness of breath, and frequent infections. Bleeding disorders and anemia, or a low red blood cell count, also can occur.
However, Fabry in general has rarely been associated with hematological (blood) disorders, with two reported cases to date of Fabry co-occurring with multiple myeloma, a type of blood cancer.
Researchers say woman’s case is a first
In this report, scientists from The First Hospital of Putian City in Fujian described the case of a 66-year-old woman who was diagnosed with both Fabry and MDS, which they said has never been documented before.
The woman had been living with type 2 diabetes for the previous 15 years, and diligently followed her prescribed diabetes treatment regimen, the team noted.
In the past five years, however, she developed several health problems, including detached retina and cataracts, hearing loss, reduced sweating, and intermittent constipation. The woman also experienced sensory and motor impairment caused by nerve damage in the upper and lower limbs, according to the team.
She underwent blood tests after experiencing dizziness and fatigue, which revealed pancytopenia — a condition marked by reductions in all three types of blood cells. Specifically, she had reductions in her red blood cells, white blood cells, and platelets.
The woman reported that her brother had died of an unknown cause associated with low platelet counts (thrombocytopenia), and her son also had reduced platelet counts.
Still, ‘no direct evidence’ linking 2 co-occurring conditions
To further investigate pancytopenia, the women underwent a blood smear analysis, which involves smearing a drop of blood onto a glass slide, staining it, and examining it under a microscope. The results showed the presence of immature white blood cells, an indication of a disease process, and immature red blood cells, consistent with an active bone marrow response to anemia.
Bone marrow aspiration — when a small amount of marrow fluid is removed for examination — showed markedly reduced cell growth, with signs of abnormal cells and decreased cellular density. A subsequent bone marrow biopsy confirmed reduced cell counts, a mild increase in immature cells, and abnormal cell features, all indicative of MDS.
A genetic analysis confirmed MDS with 5q-syndrome, a specific type of myelodysplastic syndrome characterized by a deletion on the long arm of chromosome 5. This condition primarily affects red blood cell development, leading to anemia characterized by the presence of large, immature red blood cells.
Further blood and urine test results were consistent with kidney impairment and heart failure, accompanied by heart muscle injury. An echocardiogram revealed thickening of the heart walls and valves, calcium deposits on a heart valve, a hole between the heart’s upper chambers, and impaired heart function.
A urine sediment test found mulberry bodies, clumps formed by the accumulation of Gb3 in kidney cells, which are a characteristic of Fabry. Further testing showed reduced alpha-Gal A enzyme activity and a GLA gene mutation, supporting the diagnosis of Fabry disease.
Woman’s son also had low platelet counts alongside same GLA mutation
Although several family members, including the woman’s son, had low platelet counts and shared the same GLA mutation, the team noted that Fabry’s connection to thrombocytopenia remains uncertain. Because thrombocytopenia is uncommon in Fabry disease, other factors are likely responsible, according to the researchers.
“It is important to note that there is no direct evidence linking [Fabry] with hematological abnormalities in the literature, and the coexistence of these two conditions may be incidental,” the researchers wrote. “Potential mechanisms may exist, but further investigation is warranted.”
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