SCN is a very rare condition that is diagnosed when ANC is less than 0.5 × 109/L for at least three months. Patients with SCN exhibited recurrent life-threatening infections, and a maturation arrest of bone marrow myeloid precursors at the promyelocyte-myelocyte stage of differentiation [4,5]. The boy we herein report showed typical manifestations of SCN including severe neutropenia and recurrent bacterial infections. However, the diagnosis was missed and delayed until six years of age. This issue can be explained by some reasons: Vietnam is a tropical country where infectious diseases are very popular and there is an insufficient awareness of this rare disease on the background of frequent infections even in immunocompetent pediatric population . Moreover, some infections can cause neutropenia such as tuberculosis, Dengue, measles, EV71, HIV, EBV, CMV… Therefore, neutropenia in children really is a clinical challenge for Vietnamese pediatricians especially during the first visit. Because of high prevalence of tuberculosis in Vietnam  and non-recovery by routine antibiotics, tuberculosis was suspected in our patient, reflecting an impasse in treatment of infectious diseases without adequate attention to patient’s immune disorders. Differentiating SCN from autoimmune neutropenia (AIN) requires more time for observing the clinical course, but it is important due to specific treatment [8-10]. We were confused because absolute neutrophil count of the patient was sometime elevated. Moreover, AIN is the most common type of chronic neutropenia, the patient was suspected to AIN. However, the more solumedrol he received, the more his neutrophil counts reduced. After treatment with solumedrol, the patient was overwhelming infections, and his ANC was extremely decreased (Table 1). To confirm AIN, detecting anti-neutrophil antibodies is very important but not available in Vietnam now. Carefully analyzing clinical courses of chronic neutropenia patients could contribute to critical clues for different diagnosis. In contract to SCN patients, AIN patients often have mild phenotypes with minor intercurrent infections despite severe neutropenia; their neutrophil counts could vary considerably from day to day and often rise during acute infection without corticosteroid, epinephrine, or G-CSF treatment. Since it is difficult to diagnosis AIN based only on peripheral neutrophil counts and past history, a bone marrow aspiration test is necessary for differential diagnosis [8,10]. Because the patient had severe phenotypes with life-threatening infections, chronic severe neutropenia, and reduced granulocyte cell line on bone marrow aspirate, we suspected SCN. After receiving G-CSF (6 mg/kg/24 h) his neutrophil counts were increased dramatically, excluding mutations of the patient’s G-CSF receptor gene.
To confirm SCN diagnosis, we analyzed the ELANE gene mutation firstly because it is the most common gene alteration in SCN (about 50% of SCN and nearly all of CN) [1,5,11]. There have been about 100 reported ELANE variants in SCN and CN worldwide. In exon3, we found a heterozygous missense mutation (R81P) (Figure 2). This mutation has been reported to cause severe congenital neutropenia. Because ELANE gene has a leader sequence of 29 amino acids, the codon number of the mutation may be also shown as “R52P” . SCN due to ELANE mutations causes persistent neutropenia, but surprisingly, ANC of the patient was occasionally elevated. It is difficult to explain, but exceptions may be attributable to infection at the time of blood sampling, which may transiently increase neutrophil production in the patient. Moreover, the disease phenotype is not determined by mutation alone; it can be influenced by genetic, epigenetic, environmental factors in specific time [6,12,13]. To date, this is the first SCN case confirmed by genetic analysis in Vietnam. As the estimated incidence of SCN is 1/200 000 , it is suggested that many SCN cases in Vietnam may be undiagnosed. Because G-CSF therapy is available and stem cell transplantation from HLA-identical sibling is the optimal therapeutic modality, early diagnosis is of great importance. National networks and diagnostic guideline for SCN may be helpful for us to improve these issues. Because our patient has an older sibling, we closely follow him with the idea of stem cell transplantation.
In summary, we describe a Vietnamese boy with typical phenotype of SCN but missed and delayed diagnosis. This is the first report of SCN definitively diagnosed by genetic analysis from Vietnam. The missed and delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam.