Novel ELANE gene mutation in a Korean girl with severe congenital neutropenia

Abstract

Severe congenital neutropenia is a heterozygous group of bone marrow failure syndromes that cause lifelong infections. Mutation of the ELANE gene encoding human neutrophil elastase is the most common genetic alteration. A Korean female pediatric patient was admitted because of recurrent cervical lymphadenitis without abscess formation. She had a past history of omphalitis and isolated neutropenia at birth. The peripheral blood showed a markedly decreased absolute neutrophil count, and the bone marrow findings revealed maturation arrest of myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA sequencing analysis demonstrated an ELANE gene mutation (c.607G > C; p.Gly203Arg), but her parents were negative for it. She showed only transient response after subcutaneous 15 µg/kg/day of granulocyte colony stimulating factor administration for six consecutive days. During the follow-up observation period, she suffered from subsequent seven febrile illnesses including urinary tract infection, septicemia, and cellulitis.

Keywords: Neutrophil Elastase; Severe Congenital Neutropenia.

Fig. 1

Contrast enhanced computed tomography of neck revealed conglomerated prominent enlarged lymph nodes in the internal jugular and posterior cervical chain (arrow). There was no drainable pus at the infection site.

Fig. 2

Microscopic examination of the bone marrow aspirate smear. (A) It revealed markedly decreased granulocytic precursors (Wright/Giemsa stain, × 400). (B) Myeloblasts and promyelocytes with prominent vacuolations are present, while mature neutrophils are absent (Wright/Giemsa stain, × 1,000).

Fig. 3

Direct DNA sequencing analysis demonstrated a novel ELANE gene mutation (c.607G>C; p.Gly203Arg) (arrow) (A). In the case of her parents, no mutation was detected (B, C).

Fig. 4

Change in the peripheral blood count after daily subcutaneous injections of 15 µg/kg of G-CSF (arrows). ANC, absolute neutrophil count; WBC, white blood cells.