Clinical and Genetic Characteristics of Patients with Corticosterone Methyloxidase Deficiency Type 2: Novel Mutations in CYP11B2

Özet

Corticosterone methyloxidase deficiency type 2 is an autosomal recessive disorder presenting with salt loss and failure to thrive inearly childhood and is caused by inactivating mutations of the CYP11B2 gene. Herein, we describe four Turkish patients from twofamilies who had clinical and hormonal features compatible with corticosterone methyloxidase deficiency and all had inherited novelCYP11B2 variants. All of the patients presented with vomiting, failure to thrive and severe dehydration, except one patient with onlyfailure to thrive. Biochemical studies showed hyponatremia, hyperkalemia and acidosis. All patients had normal cortisol response toadrenocorticotropic hormone stimulation test and had elevated plasma renin activity with low aldosterone levels. Three patients from thesame family were found to harbor a novel homozygous variant c.1175T>C (p.Leu392Pro) and a known homozygous variant c.788T>A(p.Ile263Asn) in the CYP11B2 gene. The fourth patient had a novel homozygous variant c.666_667delCT (p.Phe223ProfsTer35) in theCYP11B2 gene which caused a frame shift, forming a stop codon. Corticosterone methyloxidase deficiency should be considered as adifferential diagnosis in patients presenting with hyponatremia, hyperkalemia and growth retardation, and it should not be forgottenthat this condition is life-threatening if untreated. Genetic analyses are helpful in diagnosis of the patients and their relatives. Familyscreening is important for an early diagnosis and treatment. In our cases, previously unreported novel variants were identified which arelikely to be associated with the disease.