Neutropenia/lekopenia is common in childhood and the etiologies include not only acquired causes, such as infection and drugs but also inherited or acquired genetic alterations. Of the genetic causes, most well-known are the congenital neutropenia mutations, Shwachman Diamond Syndrome. On the other hand, there are patiets who have none of these underlying pathologies. Herein we report a series of patients who had mitochodrial deletion as an underlying pathology in neutropenia/lekopenia investigations.
The patients who had persistent neutropenia and/or leukopenia for at least three times were investigated for ELANE2, HAX1, G6PC3, SBDS1 and FISH analyses for myelodysplatic syndrome and were found negative for all were further analyzed with MLPA for mitochondrial deletions. The patients who had Person syndrome were excluded.
A total of 4 patients were found to have mitochondrial deletion of approximately 948 bp with MLPA assay, all in heteroplasmic state. The ages of the patients varied as 13m,16m,11y,13y and the age of onset was 10m,9m,10y,9y, respectively (M/F=1/3). DEB was negative in 2 of the patients and one of the patients were evaluated with WES for nuclear genome and was found only heterozygous for FANCG. WBC were 6300, 8100, 4200, 3300, respectively and ANC 400,300,900 and 1700. All had normal lactate/pyruvate ratio. None had finding in cardiac, auditary, ophtalmological evaluations. Two had erytroid vacuolization in bone marrow examination. None had myeloid stage arrest or dysplasia. One had megaloblastic changes in myeloid/ertrid lineages.
Mitochondrial deletions might be the underlying pathology in unexplained leukopenia/neutropenia. This might cause premature hematopoietic aging.