Abstract Objectives The coexistence of multiple genetic disorders in a single individual is more frequent in populations with high consanguinity rates. When a single diagnosis does not fully explain the clinical phenotype, the presence of additional genetic conditions should be considered. This approach is essential for accurate genetic counseling and optimal long-term management. Here, we aimed to present two siblings diagnosed with both neonatal diabetes mellitus (NDM) and leukocyte adhesion deficiency type 1 (LAD-1), a combination not previously reported. Case presentation We report two sisters born to consanguineous parents, both diagnosed with permanent neonatal diabetes mellitus and LAD-1. Genetic analysis revealed a homozygous c.-331C>G mutation in the INS promoter region and a homozygous c.388T>C mutation in the ITGB2 gene in both patients.The index case presented with hyperglycemia on the 14th postnatal day and was diagnosed with permanent NDM. She also had additional congenital anomalies, including meningomyelocele and developmental hip dislocation. Due to recurrent infections and decreased CD18 expression on leukocytes, she was subsequently diagnosed with LAD-1.The second sibling developed hyperglycemia on the second postnatal day and was diagnosed with permanent NDM. She also showed delayed umbilical cord separation, leukocytosis, and absent CD18 expression, leading to the diagnosis of LAD-1. Conclusions The coexistence of two distinct rare genetic disorders in the same individual is uncommon, and its occurrence in siblings is exceptionally rare. To our knowledge, the coexistence of LAD-1 and NDM has not been previously reported. These cases emphasize the importance of considering multiple genetic diagnoses in patients with atypical or complex clinical findings, especially in consanguineous populations. Early recognition is critical for appropriate clinical management and genetic counseling.
Türktan et al. (Sat,) studied this question.