NITA RADHAKRISHNAN, India
Super Speciality Pediatric Hospital and PG Teaching Institute Department of Pediatric Hematology OncologyPresenter of 1 Presentation
FRAME SHIFT DELETION IN GATA 2 GENE PRESENTING WITH MYELODYSPLASTIC SYNDROME ASSOCIATED ACUTE MYELOID LEUKEMIA AND INFECTIONS
Abstract
Background and Aims
GATA-2 deficiency is a novel clinical entity with protean clinical manifestations. We describe the experience of managing a child with monosomy 7 associated myeloid leukemia who was diagnosed to have a frameshift deletion in GATA2 gene.
Methods
14-year-old boy, born of non-consanguineous couple was diagnosed to have monosomy 7 associated acute myeloid leukemia following evaluation for anemia, macrocytosis and growth failure. He received standard AML chemotherapy without bone marrow transplantation which he tolerated without any life threatening infections. At initial evaluation for AML, he was noted to have black warts along the hairline of forehead which would shed off occasionally. 6 months aftere AML treatment completion, he started developing episodes of severe diarrhea caused by cryptosporidium parvum resulting in hypokalemic periodic paralysis. One episode of quadriparesis improved with potassium supplementation. Progressive weight loss was noted during this period. 14 months after AML treatment he developed bilateral lobar consolidation with fatal pulmonary haemorrhage despite aggressive antimicrobial support.
Results
Lymphocyte subset analysis showed low absolute lymphocyte count associated with absent CD 19 and CD 56 cells. Next generation sequencing for cancer predisposition genes revealed a frameshift deletion (chr3:128205727: TG>T; c.147del) resulting in amino acid change and subsequent termination of the protein, 31 amino acids downstream to codon 49 (p. Phe49LeufsTer31) was detected in the GATA2 gene. This is a loss of function mutation which is not reported in ExAC and 1000 genomes databases.
Conclusions
Looking beyond AML, helps us diagnose primary immune deficiencies that have consquences in clinical decision making and genetic counseling for the family.