1Department of Hematology, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh, India.
2Department of Paediatric Medicine, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh, India.
A 2-year-old male child born of a non-consanguineous marriage with a mixed ethnic background (father is a Punjabi and mother is from Orissa), visited to the pediatric emergency department with a history of spontaneous gum bleeding over the previous 4 days which was not resolved by general remedies. In addition, the patient suffered from episodic ecchymotic patches over the anterior abdominal wall in the previous month. There was no history suggestive of any bleeding disorders in close relatives (maternal/paternal sides). He was the second born child with an asymptomatic elder sister. On physical examination, the child had delayed developmental milestones, mongoloid slant, flat occiput, depressed nasal bridge, short hands, and simian crease, all suggestive of the DS phenotype. However, no abnormality was found in review of systems.
Karyotype analysis confirmed DS (47, XY, +21). Imaging studies confirmed the absence of any renal or cardiac malformations. Thyroid profile showed normal T3, T4, and thyroid stimulating hormone levels of 1.72, 10.57, and 3.5 units, respectively. Complete blood cell count (CBC) revealed hemoglobin level of 13.0 g/dL, white blood cell (WBC) count of 5.6×109/L, and platelet count of 292×109/L. Coagulation test showed normal prothrombin time (PT), 14 sec (reference range, 12–16 sec); prolonged activated partial thromboplastin time (aPTT), 85 sec (reference range, 26–32 sec); and normal fibrinogen level, 1.75 g/L (reference range, 2–4 g/L). Mixing study using normal pooled plasma and patient's plasma was suggestive of factor IX deficiency. Factor IX quantitative assay revealed a concentration of <1%, indicative of severe deficiency (Hemophilia B). Sequence analysis of peripheral blood for the
The hematological abnormalities in DS have been studied in order to understand their pathophysiology. The spectrum of these abnormalities includes benign conditions (neutrophilia, thrombocytopenia, and polycythemia) which usually resolve by 3 weeks of age, as well as malignancies like acute megakaryoblastic leukemia . The likely explanation for all these manifestations may be secondary to the extra copy of chromosome 21 or because of mutations involving the
Hemophilia B results from variants in the
To the best of our knowledge, this is the first report of the coexistence of DS with hemophilia B. On the other hand, there are only two reported cases of DS with hemophilia A . Though some authors argued that transient bone marrow dysfunction in DS causes the imbalance of releasing hematopoietic elements, this hypothesis cannot be applied to this case . The underlying mechanism of
In conclusion, we report here the first case of DS with hemophilia B managed with appropriate therapy. These patients should be followed up closely for preventing the disabilities as well as early detection of other complications in DS.