Combined Immunodeficiency Due To Orai1 Deficiency
Combined immunodeficiency (CID) due to ORAI1 deficiency is a form of CID due to Calcium release activated Ca2+ (CRAC) channel dysfunction (see this term) characterized by recurrent infections, congenital myopathy, ectodermal dysplasia and anhydrosis.
Epidemiology
To date, it has been reported in 6 patients in 3 families.
Clinical description
The disease is characterized by recurrent viral, bacterial, mycobacterial and fungal infections from birth, chronic diarrhea, pneumonia, meningitis, enteritis, gastrointestinal candidiasis, sepsis and otitis media. In addition, patients present at birth with congenital myopathy (see this term), characterized by non-progressive generalized muscular dysplasia. This presents as poor head control after birth, delayed ambulation and a positive Gower's sign. All patients present with ectodermal dysplasia that is characterized by hypocalcified amelogenesis imperfecta (see this term) and leads to the loss of soft dental enamel. Patients also have anhydrosis, which is characterized by inability to sweat and recurrent fever episodes associated with impaired thermoregulation.
Etiology
The disease is caused by mutations in the ORAI1 gene (12q24.31) which codes for calcium release-activated calcium channel protein 1.
Genetic counseling
Transmission is autosomal recessive.