A defect in one of the 5 enzymes related to the cortisol biosynthesis pathway (cholesterol side chain degradation enzyme, 3-beta-hydroxysteroid dehydrogenase, 17-hydroxylase, 21-hydroxylase and 11-hydroxylase) is responsible for the formation of KAH. Congenital Adrenal Hyperplasia (CAH) is seen in newborn babies with a frequency of 1/10,000-16,000. The most common 21 hydroxylase enzyme deficiency. 3-β-hydroxysteroid dehydrogenase (3βHSD) deficiency is a rare form of KAH caused by defects in the HSD3B2 gene located on chromosome 1p12, which is primarily expressed in the adrenal glands and gonads. Normally, 3βHSD catalyzes the conversion of pregnenolone to aldosterone, 17-hydroxypregnenolone (17OHPreg) to cortisol, and dehydroepiandrosterone (DHEA) to androstenedione. Defects in HSD3B2 block the conversion of precursor hormones leading to the accumulation of metabolites. We present here a 6-year-old female patient with a rare and previously unidentified 3-β-hydroxysteroid dehydrogenase (3βHSD) deficiency. A 6-year-old girl who was diagnosed with KAH at the age of 2 months in another center applied to the pediatric endocrinology outpatient clinic for follow-up and treatment. The patient, who was followed up for dehydration and vomiting, was investigated because of the large size and hyperpigmentation in the labium majus in the physical examination, and she was diagnosed with KAH. Karyotype examination was reported as 46.XX. 21 hydroxylase enzyme deficiency, which is the most common cause of KAH, was examined but found to be normal. In the examinations performed when she applied to us, she was reported as homozygous for Aldosterone: 1.31 pg/ml, 17OHP: T(p.Arg335*) mutation. The patient is currently 14 years old and is being followed up in our outpatient clinic. Although 21 hydroxylase enzyme deficiency is the most common type, 3βHSD deficiency should also be considered in the differential diagnosis since it can cause adrenal crises. Although 3βHSD deficiency can occur with adrenal crisis like classical CAH, it is particularly interesting that the mutation could not be detected early. Considering the relationship between genotype and degree of enzymatic activity when we examine similar cases, a small but insufficient residue that provides some protection in early life is thought to have activity. However, future functional studies or identification of this mutation in other cases will help clarify this point. In conclusion, 3βHSD deficiency has a variable phenotypic presentation and early diagnosis is crucial. Newborn screening is unlikely to detect 3βHSD deficiency. Genetic investigation of affected individuals in terms of 3βHSD deficiency should be kept in mind in undiagnosed patients.
15 Sep 2022 - 17 Sep 2022