Case summary
Male baby born at 37 weeks gestation following an uneventful pregnancy. Antenatal screening was declined, but at birth there was phenotypic suspicion of DS which was confirmed later by fluorescence-in-situ-hybridization and karyotype. Jaundice within the first 24-hours prompted a septic screen which demonstrated a high WCC of 107x109/l with a blast count of 80% . Flow cytometry was consistent with TAM, and GATA-1 mutations were subsequently identified.
Jaundice responded well to phototherapy and the patient was clinically stable for the first 4 days of life, however on day 5, he developed increased work of breathing requiring oxygen therapy. An echocardiogram ruled out pericardial effusion but identified a large ventricular septal defect (VSD) with moderately raised pulmonary pressures, possibly contributing to the respiratory distress. Over the next 48-hours the WCC rose to 152x109/l with concurrent hepatosplenomegly and worsening respiratory distress despite diuretic therapy. The patient commenced treatment with LDAC 1.5mg/kg once daily. A 7-day course was well tolerated with the WCC falling to 40x109/l, regression of hepatosplenomegaly and resolution of oxygen requirement (Table 1).
Leucocytosis recurred 5 days after completion of LDAC with no infectious cause identified and no improvement with antibiotics. Within 10 days of LDAC, the WCC had risen to 102x109/l with 50% blasts, hepatosplenomegaly had increased and respiratory distress had recurred necessitating reintroduction of oxygen therapy. A second course of LDAC was started but this required termination after 4 doses due to gut toxicity with necrotising enterocolitis successfully managed conservatively. The WCC did fall to 28x109/l but within a week of stopping the second course of LDAC it had risen to 102x109/l, with worsening hepatosplenomegaly and an increase in oxygen requirement, not due to deterioration in cardiac status. A third course of LDAC was started 8 days after the second course was prematurely terminated. This time a full 7-day course of LDAC was well tolerated with the WCC falling to 16x109/l. Seven days after completion of the third course of LDAC WCC had risen to 37x109/l, with increasing hepatosplenomegaly causing further respiratory distress, thus a fourth LDAC course was commenced. The WCC fell to 10x109/l following the fourth course and respiratory support was no longer required a week after completion. He has since been self-ventilating in air.
At age 5 months, three months after completion of the fourth course, the WCC is normal at 8x109/l with normal haemoglobin, platelet and neutrophil count. There is no palpable hepatosplenomegaly and the patient has been able to establish feeding, is gaining weight and developing normally.