Abstract
<title>Abstract</title> <p> Introduction Chediak–Higashi syndrome (CHS) is a rare autosomal recessive inborn error of immunity caused by biallelic mutations in the <italic>LYST</italic> gene. Population-based data on its clinical and immunological features remain scarce, particularly from Middle Eastern populations. We aimed to characterize the clinical manifestations, immunological findings, and outcomes of patients with CHS registered in the Iranian Primary Immunodeficiency Registry (IPIDR). Methods This retrospective cohort study included all patients with a confirmed diagnosis of CHS registered in the IPIDR between 2011 and 2023. Demographic, clinical, laboratory, and immunological data were extracted from registry records. Diagnosis was established based on cytological and/or molecular criteria. Data are presented using descriptive statistics. Results 23 patients with confirmed CHS were included. The median age at data extraction was 216 months (IQR: 168–363). The median age at symptom onset was 12 months (IQR: 6.5–18) and at diagnosis 24 months (IQR: 12–48), yielding a median diagnostic delay of 5.8 months (IQR: 1.75–23.25). Parental consanguinity was present in 18 patients (78.3%), and 14 patients (60.9%) were male. At final follow-up, 21 patients (91.3%) were alive, one (4.3%) had died from sepsis, and the status of one (4.3%) was unknown. The most common clinical features were recurrent respiratory and skin infections, partial oculocutaneous albinism, silvery hair, nystagmus, hepatosplenomegaly, and pancytopenia. Conclusion CHS in Iran presents early and carries a risk of life-threatening complications, underscoring the need for prompt diagnosis and close follow-up. Registry-based data such as those from the IPIDR are essential for characterizing ultra-rare disorders and informing clinical practice. Early genetic screening in high-risk families and timely HSCT referral before the accelerated phase develops should be prioritized. </p>