Neuromuscular Symptoms of ORAI1-Related Immunodeficiency

Combined immunodeficiency (CID) due to ORAI1 deficiency is an ultrarare autosomal recessive disorder characterized by the coexistence of recurrent infections, ectodermal dysplasia, autoimmunity, and myopathy. Untreated patients die in early childhood due to recurrent severe infections. This report presents a familial case of CID due to ORAI1 deficiency, caused by a homozygous loss-of-function variant c.581T>C in the ORAI1 gene. The oldest of the siblings died because of recurrent severe infections in the third year of life. His brother survived because of hematopoietic cell transplantation (HCT) but developed other symptoms of the disease. The patient achieved the ability to walk unaided at age 18 months, with a waddling gait from the beginning. His neurologic status was stable in early childhood, with mild deterioration after age 6 years. At the age of 11 years, proximal muscle weakness and borderline respiratory sufficiency are observed, with myopathic electromyography, normal level of creatine kinase, and global fatty infiltration in muscle magnetic resonance imaging, most pronounced in gluteus maximus. Additionally, dental dysplasia and heat intolerance are observed. Keywords: ORAI1 deficiency, combined immunodeficiency, ORAI1 gene, neuromuscular symptoms, myopathy.