Clinical Characteristics And Gene Analysis Of 10 Children With Congenital Agammaglobulinemia

Objective: Investigating and analyzing the phenotypes and genotypes of 10 Chinese children with congenital agammaglobulinemia to improve care plans.Methods: From April, 2015 to April, 2016, We collected 10 children with congenital agammaglobulinemia. BTK gene or IGHM gene were directly sequenced respectively based on the possible diagnosis. Clinical data of the children were collected and analyzed. We registered the information of every case in the information management system of care center for PID in china.Results: The mean age of onset of the 10 patients was 1.58±1.55 years old and the mean age at diagnosis was 7.5±3.9 years old. Of the 10 children with congenital agammaglobulinemia showing recurrent infections, low immunoglobulins and profoundly decreased B cells. Respiratory tract infection was the most common(n=9, 9/10), followed by skin infection(n=4, 4/10), otitis media(n=3, 3/10), arthritis(n=3, 3/10), rhinitis or sinusitis(n=2, 2/10), diarrhea(n=2, 2/10), meningocephalitis(n=2, 2/10), septicemia(n=1, 1/10) and osteomyelitis(n=1, 1/10). There were 9 cases performed chest CT, bronchiectasis were seen in 6 cases, pulmonary inflammation were seen in 6 cases, pulmonary atelectasis were seen in 2 cases. No abnormalities were seen in 2 cases. BTK gene mutation were identified in 9 male patients. Of the 9 BTK gene mutations, six novel mutations were identified. Three of night mutations in the BTK gene were located in the TK domain, two in the PH domain, two in the TH domain and one spanned the TH, SH3, SH2 and TK domains. A nonsense mutation in the IGHM gene was identified in one female patient(c.1069 C>T). In 10 cases, 8 cases of accepted regular and enough IVIG replacement therapy per month, and simultaneously take orally compound sulfamethoxazole tablets to prevent infection. 2 cases did not receive IVIG replacement therapy, therefor they still have recurrent infections recently. Most children is stable now with good general condition, significantly decreased frequency of infection and normal immunoglobulin level. The IVIG replacement therapy is costly. It costs more than 50% of the total household income in 9 cases, including more than 80% in 7 cases, and far more than the total household income in 2 cases. Only one in ten cases, the IVIG therapy costs less than 10% of the total household income because of enjoying relevant medical insurance policies. In 10 cases, only one case considered accepting allogeneic hematopoietic stem cell transplantation in the near future.Conclusion: All the ten patients had the characteristic of congenital agammaglobulinemia, incluinding recurrent infections, low immunoglobulins and profoundly decreased B cells.We identified the defected gene of all the ten patient by gene detection and analysis. Six novel mutations of BTK gene and one novel mutation of IGHM gene were identified. Genetic test plays a significant role in definitive and early diagnosis of congenital agammaglobulinemia and may contribute to accurate carrier detection and prenatal diagnosis. It is common to see pulmonary disease in primary antibody defects, therefor physicians should strengthen the monitoring and management of the pulmonary complications. The cost of IVIG replacement treatment therapy is a heavy burden for patients with antibody defects.