HSCT in AK2-Related Reticular Dysgenesis: 85.7% Survival at 10 Years

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Frontiers in Medicine Published April 24, 2026 Medically reviewed April 24, 2026 Study authors: Bothainah Alaqeel, Faiz Aljohani, Nora Alrumayan, Ali Al-Ahmari, Reem Mohammed, Hawazen Alsaedi, Mou… DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider HSCT for AK2-related reticular dysgenesis, but interpret findings cautiously due to small, observational data.

A retrospective single-center cohort study at King Faisal Specialist Hospital and Research Centre (2005–2025) evaluated 10 patients with genetically confirmed AK2-related reticular dysgenesis from 8 unrelated families in a high-consanguinity population. Seven patients received hematopoietic stem cell transplantation (HSCT) and were compared with the pre-transplant natural history of 3 untreated patients.

Among the 7 transplanted patients, 6 survived (85.7% survival; 6 survivors out of 7 transplanted patients) over a median follow-up of 10 years post-transplant. All 7 achieved full donor myeloid and lymphoid engraftment and robust immune reconstitution. No specific adverse event rates, discontinuations, or tolerability data were reported.

Key limitations include the retrospective single-center design, small sample size, and lack of a randomized comparator. The study’s certainty is low due to these methodological constraints. Causality cannot be inferred; only associations are reported.

Clinical relevance is constrained by the single-center, high-consanguinity setting, which limits generalizability. The authors note that early HSCT appears to enable durable engraftment and favorable long-term outcomes, supporting the importance of early diagnosis and newborn screening in similar populations.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

Reticular dysgenesis (RD), caused by biallelic variants in AK2, represents the most severe and rare form of Severe Combined Immunodeficiency, characterized by profound defects in lymphoid and myeloid lineages; however, data on its clinical spectrum and hematopoietic stem cell transplantation (HSCT) outcomes remain scarce. In this retrospective single-center study, we analyzed genetically confirmed AK2-related RD cases managed at King Faisal Specialist Hospital and Research Centre between 2005 and 2025, reviewing clinical, immunologic, genetic, and transplant-related data. Ten patients from eight unrelated families were included, most with parental consanguinity, all presenting in the neonatal period with severe infections, neutropenia unresponsive to granulocyte colony–stimulating factor, and bilateral sensorineural hearing loss. A recurrent homozygous missense variant (AK2: NM_001625.4: c.524G>C; p. Arg175Pro) was identified in nine patients, while one patient harbored a start-loss variant. Seven patients underwent HSCT at a median age of 4 months using matched sibling, haploidentical, or cord blood donors; six survived, yielding a post-transplant survival of 85.7% with a median follow-up of 10 years, and achieved full donor myeloid and lymphoid engraftment with robust immune reconstitution. These findings demonstrate that AK2-related RD presents with a distinctive neonatal phenotype and carries high pre-transplant mortality, while early HSCT enables durable engraftment and favorable long-term outcomes, supporting the importance of early diagnosis and newborn screening in high-consanguinity populations.