Phenotypic heterogeneity and management strategies for two brothers with XIAP deficiency syndrome.
10.3760/cma.j.cn511374-20251023-00623
- Author:
Hui HU
1
;
Shengnan WU
;
Kai CHEN
;
Jingbo SHAO
;
Ting ZHANG
;
Yongmei XIAO
Author Information
1. Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China. xiaoym@shchildren.com.cn.
- Publication Type:English Abstract
- MeSH:
Humans;
Male;
X-Linked Inhibitor of Apoptosis Protein/deficiency*;
Child;
Genetic Diseases, X-Linked/therapy*;
Phenotype;
Siblings;
Retrospective Studies;
Hematopoietic Stem Cell Transplantation
- From:
Chinese Journal of Medical Genetics
2026;43(2):123-128
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency.
METHODS:This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01).
RESULTS:Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%.
CONCLUSION:For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
