Two novel <i><scp>HSD</scp>3B2</i> missense mutations with diverse residual enzymatic activities for Δ5‐steroids

Takasawa, Kei; Ono, Masafumi; Hijikata, Atsushi; Matsubara, Yosuke; Katsumata, Noriyuki; Takagi, Motoki; Morio, Tomohiro; Ohara, Osamu; Kashimada, Kenichi; Mizutani, Shuki

doi:10.1111/cen.12394

Cited by 16 publications

(15 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The level of 17αOHP is high in cord blood during the first 1–2 days of life, and stress from other illnesses may result in the 17αOHP remaining high in unaffected neonates. Furthermore, in other forms of CAH, including 11-hydroxylase deficiency (11OHD), 3β-hydroxysteroid dehydrogenase deficiency (3βHSDD), and P450 oxidoreductase deficiency (PORD), 17αOHP may be elevated to almost the same level as that of 21OHD [ 32 ]. For further improving PPV in 21OHD screening, measuring other biomarkers with high specificity for 21OHD would be required.…”

Section: Potential Issues Of Testing Practices In the Newborn Screening For Cah In Japanmentioning

confidence: 99%

“…In addition to improving the efficiency of 21OHD screening, the steroid profile assay by LC-MS/MS may bring further advantage to the screening, that is, assisting definitive diagnosis of 21OHD [ 34 ]. Although 21OHD can be diagnosed endocrinologically, the procedures and cutoff criteria are complicated because other rare forms of CAH, such as 11OHD, PORD, and 3βHSDD, should be differentiated from the diagnosis of 21OHD as we described in the previous section [ 32 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. The nonspecific increase in 17αOHP levels in other forms of CAH has been considered as a potential clinical pitfall.…”

Section: Potential Issues Of Testing Practices In the Newborn Screening For Cah In Japanmentioning

confidence: 99%

See 1 more Smart Citation

Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

Tsuji‐Hosokawa

Kashimada

2021

IJNS

Self Cite

View full text Add to dashboard Cite

Congenital adrenal hyperplasia (CAH) is an inherited disorder caused by the absence or severely impaired activity of steroidogenic enzymes involved in cortisol biosynthesis. More than 90% of cases result from 21-hydroxylase deficiency (21OHD). To prevent life-threatening adrenal crisis and to help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH have been introduced in numerous countries. In Japan, the NBS for CAH was introduced in 1989, following the screenings for phenylketonuria and congenital hypothyroidism. In this review, we aim to summarize the experience of the past 30 years of the NBS for CAH in Japan, composed of four parts, 1: screening system in Japan, 2: the clinical outcomes for the patients with CAH, 3: various factors that would impact the NBS system, including timeline, false positive, and LC-MS/MS, 4: Database composition and improvement of the screening program.

show abstract

Section: Potential Issues Of Testing Practices In the Newborn Screening For Cah In Japanmentioning

confidence: 99%

Section: Potential Issues Of Testing Practices In the Newborn Screening For Cah In Japanmentioning

confidence: 99%

Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

Tsuji‐Hosokawa

Kashimada

2021

IJNS

Self Cite

View full text Add to dashboard Cite

show abstract

“…We synthetized the studies published according to the mentioned methodology in Table 1 [ 5 , 22 , 25 , 26 , 27 , 31 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].…”

Section: Methodsmentioning

confidence: 99%

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency

et al. 2022

View full text Add to dashboard Cite

We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3βHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients’ age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also—mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing’ syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison’s disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem–mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as “novel pathogenic mutation” (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3βHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

show abstract

“…These two enzymes share and catalyze the same reactions, although the Michaelis–Menten constant ( K m) for 3β-HSD2 is about 10-fold higher than that of 3β-HSD1 [6]. Overall, 43 female patients with or without virilization have been described so far, accounting for 26 reported mutations (Figure 2 and Supplementary Table S1) [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. While severe loss-of-function mutations predict the neonatal salt-wasting (SW) phenotype, for missense mutations the correlation is good only with regard to mineralocorticoid (MC) deficiency.…”

Section: 3β-hydroxysteroid Dehydrogenase Type 2 Deficiency (3β-hsd2d)mentioning

confidence: 99%

46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features

Baronio

Ortolano

Menabò

et al. 2019

IJMS

View full text Add to dashboard Cite

The term ‘differences of sex development’ (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, or anatomical sex. Disorders of steroidogenesis comprise autosomal recessive conditions that affect adrenal and gonadal enzymes and are responsible for some conditions of 46,XX DSD where hyperandrogenism interferes with chromosomal and gonadal sex development. Congenital adrenal hyperplasias (CAHs) are disorders of steroidogenesis that mainly involve the adrenals (21-hydroxylase and 11-hydroxylase deficiencies) and sometimes the gonads (3-beta-hydroxysteroidodehydrogenase and P450-oxidoreductase); in contrast, aromatase deficiency mainly involves the steroidogenetic activity of the gonads. This review describes the main genetic, biochemical, and clinical features that apply to the abovementioned conditions. The activities of the steroidogenetic enzymes are modulated by post-translational modifications and cofactors, particularly electron-donating redox partners. The incidences of the rare forms of CAH vary with ethnicity and geography. The elucidation of the precise roles of these enzymes and cofactors has been significantly facilitated by the identification of the genetic bases of rare disorders of steroidogenesis. Understanding steroidogenesis is important to our comprehension of differences in sexual development and other processes that are related to human reproduction and fertility, particularly those that involve androgen excess as consequence of their impairment.

show abstract

Two novel HSD3B2 missense mutations with diverse residual enzymatic activities for Δ5‐steroids

Cited by 16 publications

References 25 publications

Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency

46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features

Contact Info

Product

Resources

About