scholarly journals A Case of 3β-Hydroxysteroid Dehydrogenase Type II (HSD3B2) Deficiency Picked up by Neonatal Screening for 21-Hydroxylase Deficiency: Difficulties and Delay in Etiologic Diagnosis

2007 ◽  
Vol 68 (4) ◽  
pp. 204-208 ◽  
Author(s):  
Anna Nordenström ◽  
Maguelone G. Forest ◽  
Anna Wedell
Keyword(s):  
Neonatal Screening ◽  
Hydroxysteroid Dehydrogenase ◽  
Type Ii ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency ◽  
Etiologic Diagnosis

scholarly journals Delayed Diagnosis of Congenital Adrenal Hyperplasia with Salt Wasting Due to Type II 3β-Hydroxysteroid Dehydrogenase Deficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2076-2080 ◽  
Author(s):  
Trine H. Johannsen ◽  
Delphine Mallet ◽  
Harriet Dige-Petersen ◽  
Jørn Müller ◽  
Katharina M. Main ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Delayed Diagnosis ◽  
Bone Age ◽  
Hydroxysteroid Dehydrogenase ◽  
Type Ii ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency ◽  
Premature Pubarche

Abstract Classical 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3β-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17α-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3β-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly elevated Δ5-steroids, in particular 17α-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated Δ5-/Δ4-steroid ratios. Sequencing of the type II 3β-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17α-hydroxyprogesterone were found on blood spots from Guthrie’s test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3β-HSD gene. Because neonatal diagnosis could have prevented life-threatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology.

scholarly journals 3?-hydroxysteroid dehydrogenase type II deficiency on newborn screening test

2014 ◽  
Vol 58 (6) ◽  
pp. 650-655 ◽  
Author(s):  
Vitor Guilherme Brito de Araújo ◽  
Renata Santarem de Oliveira ◽  
Kallianna Paula Duarte Gameleira ◽  
Cátia Barbosa Cruz ◽  
Adriana Lofrano-Porto
Keyword(s):  
Newborn Screening ◽  
Screening Test ◽  
Hydroxysteroid Dehydrogenase ◽  
Screening Tests ◽  
Adrenal Crisis ◽  
Type Ii ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Genital Ambiguity ◽  
21 Hydroxylase Deficiency

3b-hydroxysteroid dehydrogenase II (3β-HSD) deficiency represents a rare CAH variant. Newborns affected with its classic form have salt wasting in early infancy and genital ambiguity in both sexes. High levels of 17-hydroxypregnenolone (Δ517OHP) are characteristic, but extra-adrenal conversion to 17-hydroxyprogesterone (17OHP) may lead to positive results on newborn screening tests. Filter paper 17OHP on newborn screening test was performed by immunofluorometric assay, and serum determinations of 17OHP and Δ517OHP, by radioimmunoassay. A 46,XY infant with genital ambiguity and adrenal crisis at three months of age presented a positive result on newborn screening for CAH. Serum determinations of 17OHP and Δ517OHP were elevated, and a high Δ517OHP/cortisol relation was compatible with the diagnosis of 3β-HSD deficiency. Molecular analysis of the HSD3B2 gene from the affected case revealed the presence of the homozygous p.P222Q mutation, whereas his parents were heterozygous for it. We present the first report of 3β-HSD type II deficiency genotype-proven detected at the Newborn Screening Program in Brazil. The case described herein corroborates the strong genotype-phenotype correlation associated with the HSD3B2 p.P222Q mutation, which leads to a classic salt-wasting 3β-HSD deficiency. Further evaluation of 17OHP assays used in newborn screening tests would aid in determining their reproducibility, as well as the potential significance of moderately elevated 17OHP levels as an early indicator to the diagnosis of other forms of classic CAH, beyond 21-hydroxylase deficiency.

The prevalence of the non-classical form of congenital adrenal hyperplasia as exemplified (by the population of the Moscow region)

2013 ◽  
Vol 59 (4) ◽  
pp. 18-22
Author(s):  
T A Ionova ◽  
A N Tiul'pakov ◽  
S G Kalinenkova
Keyword(s):  
Neonatal Screening ◽  
Moscow Region ◽  
Hydroxylase Deficiency ◽  
Classical Form ◽  
True Incidence ◽  
Monogenic Diseases ◽  
Frequent Mutations ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Autosomal Recessive Pattern

The non-classical form of 21-hydroxylase deficiency (NC21OH) is one of the most common monogenic diseases inherited in the autosomal-recessive pattern. The incidence of this condition in the Russian population, unlike that of its classical variant, remains to be elucidated. Aim. The objective of the present study was to estimate the true incidence of NC21OH based on the prevalence of the two most frequent mutations associated with this disease. A total of 998 randomly selected blood spots were obtained in the course of neonatal screening of the children born within one calendar year at the territory of the Moscow region. The incidence of the disease was calculated with the use of Hardi-Weinberg equation. The minimal prevalence rate of NC21OH in the population of the Moscow region was estimated to be 1:2206. The level of 17-hydroxyprogesterone (17-OHP) calculated based on the results of the screening studies can not be used to identify the carriers of the pathology of interest whereas neonatal screening allows to diagnose no more than 90% of the cases of NC21OH.

Benefits of Neonatal Screening for Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) in Sweden

PEDIATRICS ◽  
1998 ◽  
Vol 101 (4) ◽  
pp. e11-e11 ◽  
Author(s):  
Astrid Thilén ◽  
Anna Nordenström ◽  
Lars Hagenfeldt ◽  
Ulrika von Döbeln ◽  
Claes Guthenberg ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

scholarly journals Neonatal Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

1986 ◽  
Vol 62 (6) ◽  
pp. 683-696 ◽  
Author(s):  
Masaru FUKUSHI ◽  
Osamu ARAI ◽  
Yoshikiyo MIZUSHIMA ◽  
Nobuo TAKASUGI ◽  
Kenji FUJIEDA ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Neonatal Screening ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

scholarly journals Failure of Cortisone Acetate Treatment in Congenital Adrenal Hyperplasia because of Defective 11β-Hydroxysteroid Dehydrogenase Reductase Activity*

1999 ◽  
Vol 84 (4) ◽  
pp. 1210-1213 ◽  
Author(s):  
Anna Nordenström ◽  
Claude Marcus ◽  
Magnus Axelson ◽  
Anna Wedell ◽  
E. Martin Ritzén
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Reductase Activity ◽  
Urinary Metabolites ◽  
Hydroxysteroid Dehydrogenase ◽  
Cortisone Acetate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genetic Lesion ◽  
21 Hydroxylase Deficiency ◽  
Very High

Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone. It is known that certain patients with congenital adrenal hyperplasia require very high substitution doses of cortisone acetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2·day), was examined. The activation of cortisone to cortisol was assessed by measuring urinary metabolites of cortisone and cortisol. The patient’s inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11β-hydroxysteroid dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron junctions of the 11β-hydroxysteroid dehydrogenase type1 gene (HSD11L) were sequenced without finding any mutations, but a genetic lesion in the promoter or other regulatory regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of hydrocortisone, rather than cortisone acetate, for substitution therapy in adrenal insufficiency.

scholarly journals Two girls with a neonatal screening-negative 21-hydroxylase deficiency requiring treatment with hydrocortisone for virilization in late childhood

2021 ◽  
Vol 30 (3) ◽  
pp. 143-148
Author(s):  
Shinsuke Onuma ◽  
Tomoya Fukuoka ◽  
Yoko Miyoshi ◽  
Miho Fukui ◽  
Yoshinori Satomura ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Late Childhood ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency
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