The Clinical, Immunohematological, and Molecular Study of Iranian Patients with Severe Congenital Neutropenia

Abstract

Severe congenital neutropenia (SCN) is a rareE primary immunodeficiency disorder characterized by early onset recurrent infections in association with persistent severe agranulocytosis. To identify the clinical, immunohematological, and molecular characteristics of patients with SCN, 18 Iranian patients with the mean age of 8.8 +/- 5.8 years were investigated in this study. All of these patients experienced severe neutropenia; the mean of absolute neutrophil count was 281.4 +/- 137.7 cells/mm3. Bone marrow findings were typified by a myeloid maturation arrest at the promyelocyte-myelocyte stage in these patients. Molecular analysis revealed different mutations in the ELA-2 gene of one patient and in the HAX-1 gene of another three patients. The most common presenting complaints in these patients were superficial abscesses, oral ulcers, cutaneous infections, omphalitis, and pneumonia. During the course of illness, all patients developed mucocutaneous manifestations, and 16 cases had respiratory infections. The most commonly manifestations were abscesses, oral ulcers, pneumonia, periodontitis, otitis media, cutaneous infections, mucocutaneous candidiasis, and acute diarrhea. Three patients died because of a severe infection. Although SCN is a rare disorder, early onset of severe and recurrent infections should always raise a suspicion, which deserves further evaluation for detecting such disorder.

Severe Congenital Neutropenia or Hyper-IgM Syndrome? A Novel Mutation of CD40 Ligand in a Patient with Severe Neutropenia

“…In this report, we present a case with consistent neutropenia who was clinically diagnosed as SCN, but where molecular studies indicated a diagnosis of CD40LD. While hematological abnormalities usually occur in association with neutropenia in SCN patients [1, 2], eosinophilia and monocytosis were not documented in this case, which is similar to other SCN patients in Iran [5]. Although the patient did not have a decreased serum level of IgA, and his serum IgM level was also within the normal range, the diagnosis of CD40LD was confirmed by mutational analysis.…”

“…Early diagnosis and appropriate management remain the keys to prevent such complications [5]. Due to advances in immunological and molecular diagnostic techniques, a definitive diagnosis of most primary immunodeficiency diseases can now be easily obtained.…”

“…Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease characterized by recurrent severe infections and persistent severe neutropenia [1,2,3,4,5,6]. CD40 ligand deficiency (CD40LD), previously known as a subgroup of Hyper-IgM syndromes, is a rare combined T and B cell immunodeficiency, characterized by recurrent severe infections, markedly decreased serum levels of IgG and IgA and normal or elevated concentrations of serum IgM [6,7,8,9,10].…”

Clinical, Laboratory and Molecular Approach to Ten Children with Congenital Neutropenia

“…Sık ve ağır enfeksiyon varlığında hastaların laboratuvar değerlendirilmesinde algoritmada hemogramın ilk basamak inceleme olduğu ve total beyaz kan hücresi sayısı yanısıra dağılıma da dikkat edilmesi gerektiği unutulmamalıdır. Periferik yaymada nötropeninin yanı sıra kompansatris monosit ve eozinofil sayısında artış ile birlikte tekrarlayan enfeksiyon atakları nedeniyle serum immunoglobulin düzeylerinde yükseklik AKN olgularında görülebilmektedir (1,5,11). Olgu 7'de de belirgin eosinofili ve tüm immünoglobulin izotiplerinde artış gözlenmiştir.…”

A novel HAX1 gene mutation in severe congenital neutropenia (SCN) associated with neurological manifestations

“…SCN3 patients, who carry homozygous nonsense mutations that are common to both transcript variants 1 and 2 of the HAX1 gene, show neurological manifestations in addition to neutropenia [5,8]. So far, the nonsense mutations in the HAX1 gene have been described in SCN3 patients of German [11], Japanese [10], Turkish [8,11], Iranian [8,13], Swedish [4,5], Kurdish [5], Ashkenazi Jewish [14], and British [14] ethnicity. We have recently reported the only missense mutation, encoding for Phe141-Leu, in SCN3 patients from two unrelated Arab families [7].…”