Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients.
Haematologica
; 103(8): 1278-1287, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-29724903
ABSTRACT
Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Germ-Line Mutation
/
Young Adult
/
GATA2 Deficiency
Type of study:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Infant
/
Middle aged
/
Newborn
Country/Region as subject:
Europa
Language:
En
Journal:
Haematologica
Year:
2018
Document type:
Article
Affiliation country:
France