Clinical Characteristics and Genetic Profiles of 44 Patients with Severe Combined Immunodeficiency (SCID): Report from Shanghai, China (2004–2011)

Abstract

Severe combined immunodeficiency (SCID), a rare type of genetic associated immune disorder, is poorly characterized in mainland China. We retrospectively reviewed 44 patients with SCID who received treatment from 2004 to 2011 in Shanghai, China, and herein summarize their clinical manifestations and immunological and preliminary genetic features. The male-to-female ratio was 10:1. Twenty five patients presented with X-SCID symptoms. Only one patient was diagnosed before the onset of symptoms due to positive family history. The mean time of delay in the diagnosis of X-SCID was 2.69 months (range, 0.5-8.67). Thirty-seven of the 44 patients died by the end of 2011 with the mean age of death being 7.87 months (range, 1.33-31). Six patients received hematopoietic stem cell transplantation (HSCT); only one of them survived, who was transplanted twice. The time between onset and death was shorter in the HSCT-treated group compared with the untreated group (2.87 ± 1.28 and 3.34 ± 0.59 months, respectively), probably due to active infections during transplantation. Bacillus Calmette-Guérin (BCG) complications occurred in 14 of the 34 patients who received BCG vaccination. Transfusion-induced graft-versus-host disease occurred in 5 patients. Total 20 mutations in interleukin-2 receptor subunit gamma (IL2RG) were identified in 22 patients, including 11 novel mutations. Most patients were misdiagnosed before referred to our SCID Center. Therefore, establishing more diagnostic centers dedicated to the care of PID and accessible by primary immunodeficiency patients will facilitate early, correct diagnosis and better care of SCID in China.

Disseminated Bacille Calmette‐Guérin infection in a patient with severe combined immunodeficiency caused by JAK3 gene mutation

“…SCID patients have an approximately 400‐fold increase in risk of having localized BCG complication and 33 000‐fold increase in risk of having disseminated complications compared to the general population . However, another study in Shanghai revealed a different result; 58% of the patients with SCID who were inoculated with BCG had BCG‐related manifestations, of which 15% were disseminated BCG vaccine complications, and 85% were local complications . In disseminated BCG infection, involvement of extra‐regional lymph nodes, skin, and lungs is common, whereas involvement of liver, spleen, and bones is unusual .…”

BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

“…However, reports of 1 in 2,500 vaccinees presenting with localized BCG complications and 1 in 100,000 developing disseminated complications represent a fair estimate of the prevalence of such complications 1 9 . When focused exclusively on patients diagnosed with SCID, the prevalence of BCG complications has been estimated to be higher than in the general population 10-12 , although definitive impact has not previously been established.…”

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade's Experience

“…The dominant phenotype of SCID varies according to the country. For example, in China, 25 of 44 SCID patients had X-linked SCID [12], and in Serbia and Montenegro, 12 of 21 patients with SCID and Omenn syndrome belonged to the T -B -NK + SCID phenotype; 11 had mutations in RAG1 or RAG2 and 1 had mutations in the Artemis gene [3]. In Greece, 12 of 30 SCID patients (40%) were T -B -NK + [13].…”