Kiểu hình và kiểu gen của trẻ mắc tăng sản thượng thận bẩm sinh thiếu 21-hydroxylase phát hiện qua sàng lọc sơ sinh

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive inherited diseases with 95% cases of mutations in the CYP21A2 gene, which encodes the enzyme 21-hydroxylase (21-OH). The consequence of deficiency of the enzyme 21-OH is the failure to synthesize the hormone cortisol, in severe cases, can be followed by aldosterone deficiency. In acute exacerbation, it will lead to salt and water waste, and if not promptly and properly treated, it will lead to death. The phenotype of this disease is characterized by 3 types depending on the level of residue enzyme activity: salt wasting (SW), simple virilization (SV), and non-classical form (NC). A case series study of 54 children diagnosed with CAH got the result of high-risk CAH in newborn screening to evaluate genotypes and phenotypes of patients with CAH due to 21-OH deficiency detected by newborn screening at the Vietnam National Children's Hospital for 5 years (June 2017 to September 2022). The results showed that the median age of diagnosis in 54 children (30 males, 24 females), is 21 days old, the earliest as 2 days and the latest as 4 months. 49/54 (90.7%) presented with SW, and 24 of those cases had adrenal insufficiency at the time of diagnosis; 5/54 (9.3%) - SV; no cases of NC form has been detected. 21 cases had molecular analysis results and detected pathogenic mutations. The total number of detected mutations was 17, the most common mutations are c.515T>A (p.I172N) (21.4%), PM CYP21A1P/CYP21A2 (16.7%), del promoter - exon 3 (11.9%), g.655A/C>G (I2G) (9.5%). Phenotype prediction by genotype is more likely in SW (100%) and less likely in SV (44.4%). Newborn screening test is meaningful in the early diagnosis of severe cases of CAH with SW. Phenotype prediction by genotype was highly correlated in SW and poorly correlated in SV.