Background: 17β-Hydroxysteroid Dehydrogenase3 (17b-HSD3) deficiency is a rare autosomal recessive disorder, caused by a mutation of the HSD17B3 gene. The phenotypic spectrum ranges from normal-appearing female external genitalia to microphallus with hypospadias and variable degrees of genital ambiguity. 17b-HSD3 deficiency phenotype is variable, leading to misdiagnosis especially with partial androgen insensitivity syndrome and 5alfa reductase deficiency.
Aim: We aimed to evaluate clinical and laboratory features of ten patients with HSD17B3 mutations and phenotype/genotype correlation.
Patients and methods: Data of 10 46,XY patients with HSD17B3 mutations were reviewed retrospectively.
Results: Ten patients were identified from seven pedigrees. Range of age at presentation was 0.517.3 years old. Only one patient presented in early infancy. Presenting symptoms were inguinal hernia and masses in six patients and hirsutism, primary amenorrhea in three patients and hypospadias and cryptorchidism in one patient. All patients were from consanguineous families. Six of the nine patients had female appearance of external genitalia and three patients had mild cliteromegaly or a prominent clitoris and one patient had penoscrotal hypospadias and cryptorchidism at presentation. All patients except one were raised as female. Müllerian structures were absent in all patients. Five of seven mutations were reported previously (c.[139A>G];[704T>C], c.[182G>A];[182G>A], c.[277+4A>T];[277+4A>T], c.[277G>A];[277G>A], c.[607-1G>A];[607-1G>A]. Two mutations are first time reported in this study (c.[167C>T]; [167C>T], and c.[639_640 insA];[639_640 insA]. The median testosterone/androstenedione ratio after a short hCG stimulation test was evaluated in five patients and ratio of four patients was <0.8. Bilateral gonadectomy were performed in all patients reared as female. The histopathology of the gonads was consistent with testis and spermatic cord and no malignancy was seen.
Conclusion: 17b-HSD3 deficiency presents with a wide spectrum of clinical findings. There seems to be no phenotype/genotype correlation. Molecular diagnosis guide families for differential genetic counseling.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology