Case Study: 30 Year-Old Female with Pancytopenia and Fatigue
A 30-year-old woman is referred by her primary care physician for evaluation of pancytopenia. In addition to fatigue and easy bruising, the patient reports a history of unexplained lower extremity swelling and recurrent herpes infections. Her family history is significant for a maternal uncle and grandmother who both died from acute myeloid leukemia. Laboratory studies reveal:
| White blood cells | 2.0 K/μL (4.0-11.0 K/μL) |
| Absolute neutrophil count | 0.4 k/μL (1.56-6.13 k/μL) |
| Absolute lymphocyte count | 0.34 k/μL (1.18-3.74 k/μL) |
| Hemoglobin | 7.8 g/dL (13.5-17.5 g/dL) |
| Platelets | 24 k/μL (150-400 k/μL) |
| B cells | 0/μL (0.07-0.7 k/μL) |
| T cells | 0.34/μL (0.67-2.95 k/μL) |
| Natural killer cells | 0.1/μL (0.08-1.15 k/μL) |
Bone marrow biopsy demonstrated 20 percent cellularity with megakaryocytic atypia including micromegakaryocytes and erythroid dysplasia without increased CD34+ blasts. Cytogenetic studies found trisomy eight in three of 20 metaphases examined.
For which inherited mutation is testing warranted?
- RUNX1
- GATA2
- FLT3
- TP53
- NPM1
Answer
- GATA2
Explanation
This patient has myelodysplastic syndrome (MDS) in the background of a germline mutation in the GATA2 gene responsible for GATA2-deficiency syndrome.1 Haploinsuffiency in the GATA2 gene leads to a wide range of hematologic consequences, including aplastic anemia, chronic neutropenia, and an increased risk of developing MDS or acute myeloid leukemia (AML). Patients characteristically will have low or absent B cells, T cells, and natural killer cells. Recurrent herpes infections, lymphedema, and atypical mycobacterial infections are common in GATA2-deficiency syndromes. Identification of familial causes of MDS/AML is critical when screening potential sibling donors for stem cell transplantation as well as identifying additional carriers within a family.2
Case study submitted by James Cooper, MD, of the National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
References- Ganapathi KA, Townsley DM, Hsu AP, et al. GATA2 deficiency–associated bone marrow disorder differs from idiopathic aplastic anemia. Blood. 2015 125:56-70.
- Babushok DV, Bessler M. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?. Best Pract Res Clin Haematol. 2015 28:55-68.
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