Analysis Of Clinical Manifestations And Gene Mutations In Infants With 21-Hydroxylase Deficiencies

Objective: The aim of this study was to analyze and summarize the clinical symptoms and genetic characteristics of infants with 21-hydroxylase deficiencies (21-OHD). Methods: A total of 50 infants, diagnosed with 21-OHD deficiencies, were included in the study. Clinical data, including age, sex, chief complaint, history of present illness, family history, past medical history, clinical symptoms, and comprehensive physical examination reports, were collected for analyses. Blood biochemistry parameters, including ad renocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), testosterone, progesterone, cortisol, electrolytes, and genetic testing results, were also gathered and analyzed. Results: Of the 50 infants, the number of each of the three types of 21-OHD, including simple virilizing type, salt-wasting type, and non-classic type, were 15, 26, and 9, respectively. Symptoms of the 15 simple virilizing type infants were not apparent. However, their clinical signs were prominent, manifesting as abnormalities of the external genitalia. In contrast, the 26 salt-wasting type infants experienced apparent clinical symptoms, such as anorexia and diarrhea. Some patients also showed signs of external genital abnormalities. Those non-classic type infants had no overt clinical symptoms or signs. The current study found that levels of hormones in infants with 21-OHD were different than normal, with varying degrees. ACTH, 17-OHP, testosterone, and progesterone increased, while serum cortisol decreased, in varying degrees, compared to the normal range. The increase of ACTH, 17-OHP, and progesterone in simple virilizing type or non-classic types was lower than that of the salt-wasting type (both P<0.05). However, there were no differences in serum testosterone levels among the three types (all P>0.05). Moreover, serum cortisol levels of simple virilizing and non-classic types were lower than those of the salt-wasting type (both P<0.05). Predictably, the serum electrolyte panel showed significant differences in hyponatremia and hyperkalemia levels between the salt-wasting type and the other two types (both P<0.05). Parents of the 38 infants provided written consent to undergo CYP21A2 gene testing. Sanger sequencing revealed a total of 13 types of point mutations in 76 alleles, of which the intron 2 splice mutation (I2G) was the most common, presenting in 23 alleles and accounting for 30.3%. This was followed by c.518T>A (p. I173N) mutation, which was detected in 9 alleles (11.8%). In 5 patients, only one-point mutation was found in one allele. In the other 4 patients, no gene mutations were detected. Regarding the 5 cases with only one-point mutation and the 4 cases with no-point mutations, multiplex ligation-dependent probe amplification (MLPA) was used for further detection. Results showed that 6 of them had large fragment deletion. Combiningthose two genetic testing methods could yield a positive rate as high as 92.1%. Conclusion: Early diagnosis of 21-OHD should be based on clinical symptoms, signs, laboratory findings, and genetic tests.