Infants with Down syndrome are more prone to transient abnormal myelopoiesis. A small percentage of this condition can be fatal, yet they are more prone to develop acute myeloid leukemia if harboring GATA1 mutation.
Aim of the Work was to screen infants with Down syndrome for peripheral GATA1 mutation by sequencing of exon2 and to correlate it with clinical and laboratory parameters.
The study included 79 patients with Down syndrome aged 1–90 days from the outpatient Genetics Clinic, Children's Hospital, Ain Shams University. Complete blood count with manual differential leukocytes count and blast cells count was assessed to all patients.By peripheral blast count patients were divided into three groups, Group A with peripheral blast count more than 10%, group B with blast count >0–10% and group C with no detected blasts in peripheral blood. Mutation analysis of exon2 of GATA1 gene was performed by Sanger sequencing to 15 cases based on results of blast cells count.
The median age of patients was 23.5 days. Prematurity was detected in only 6.3% of patients. Eighteen percent of DS patients (15 of 78) had blasts on blood smears (range 1%>60%). %). Group A included 4 patients, group B 11 patients and Group C 63 patients. The patients in group A were younger in age than patients in group B and C. Those 15 patients were divided into two groups: Mutation positive group: 4 patients, all of them had blast cells count >10% and Mutation negative group: 11 patients. The peripheral blast cells% was significantly higher in the mutation positive than mutation negative group. The only patient presented with splenomegaly was positive for the mutation of exon 2 of GATA-1 gene.There was higher leucocytic count in patients with positive mutations compared to negative ones.One patient with positive GATA1 mutation developed AMKL and died of disease, he had initial blast count more than 10% in peripheral blood.
All patients with positive GATA1 mutations had blasts>10% in their peripheral blood. One of the mutation positive patients developed acute myeloid leukemia. We conclude that blast cells count in peripheral blood combined with peripheral GATA1 mutation analysis can be used for close follow up of patients for early detection of acute megakaryocytic leukemia in infants with Down syndrome.