Transition in the field of Disorders of Sex Development (DSD): A case of late diagnosed 5α-reductase deficiency illustrates complex requirements

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
W Birnbaum ◽  
L Marshall ◽  
O Hiort
Keyword(s):  
Disorders Of Sex Development ◽  
Reductase Deficiency ◽  
Sex Development ◽  
5Α Reductase Deficiency

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Chupong Ittiwut ◽  
Jaturong Pratuangdejkul ◽  
Vichit Supornsilchai ◽  
Sasipa Muensri ◽  
Yodporn Hiranras ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Mendelian Inheritance ◽  
Novel Mutations ◽  
Cross Sectional ◽  
Genetic Characteristics ◽  
Reductase Deficiency ◽  
Testosterone Production ◽  
Sex Development ◽  
5Α Reductase Deficiency

AbstractBackground:Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th–12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD.Methods:A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of theResults:Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations inConclusions:Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of

The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia

2015 ◽  
Vol 28 (9-10) ◽  
Author(s):  
Nasir A.M. Al-Jurayyan ◽  
Sharifah D.A. Al Issa ◽  
Abdulrahman M.H. Al Nemri ◽  
Hessah M.N. Al Otaibi ◽  
Amir M.I. Babiker
Keyword(s):  
Saudi Arabia ◽  
Wide Spectrum ◽  
Disorders Of Sex Development ◽  
Case Series ◽  
Clinical Spectrum ◽  
University Hospital ◽  
Androgen Insensitivity ◽  
Reductase Deficiency ◽  
Sex Development ◽  
Number Of Patients

AbstractThe term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. The spectrum of the 46XY (DSD) is so broad. In this study, we reviewed the clinical spectrum of a cohort of patients with 46XY DSD in a tertiary institute in the Middle East over two decades.To define the clinical spectrum of 46XY DSD in a major teaching hospital, Riyadh, Saudi Arabia.This is a retrospective, case series hospital-based study. The case notes, laboratory investigations, and imaging studies were reviewed for patients with 46XY DSD over a 20 years period (1989–2010) at King Khalid University Hospital, Riyadh, Saudi Arabia. Molecular genetics were not available in all patients.During the period under review; a total of 56 patients were seen with 46XY DSD due to variable etiologies. Androgen insensitivity syndromes (AIS) and 5-α-reductase deficiency were among the commonest (44.6%), with multiple siblings involvement within the family. Of these, 16 patients were showing variable degrees of insensitivity ranging between complete (n=5, 31.2%) and partial (n=11, 68.8%) insensitivity, whereas in nine patients the diagnosis of 5-α-reductase deficiency was entertained based on hormonal studies. Of interest to see was a high number of patients (n=14, 25%) either with a localized congenital anomalies such as the cloacal anomalies or generalized congenital malformations following the pattern of certain syndromes.A wide spectrum of causes were noted. Androgen insensitivity syndrome was the commonest. In Saudi Arabia, where consanguineous mating is high, 5-α-reductase is also a common cause of 46XY DSD.

scholarly journals 46 XY DISORDER

2016 ◽  
Vol 23 (10) ◽  
pp. 1202-1208
Author(s):  
Muhammad Naveed Najeeb ◽  
Sadiq Hussain Malik ◽  
Sheikh Khurram Salam Sehgal ◽  
Ameer Ahmad Malik ◽  
Saqib Mehmood
Keyword(s):  
Physical Examination ◽  
Study Design ◽  
Gonadal Dysgenesis ◽  
Disorders Of Sex Development ◽  
Serum Testosterone ◽  
Androgen Insensitivity Syndrome ◽  
Base Line ◽  
Reductase Deficiency ◽  
Androgen Synthesis ◽  
Sex Development

Objectives: The Disorders of Sex Development are classified as 46, XY DSD,46, XX DSD and Chromosomal DSD according to the chromosomal constitution of the affectedpersons. 46, XY DSD is further classified into Androgen Synthetic Defect, Androgen InsensitivitySyndrome Gonadal Dysgenesis, 5-Alpha Reductase Deficiency, Persistent Mullerian DuctSyndrome and Isolated Hypospadias according to the pathophysiology of the disease. Theaim of present study was to classify 46, XY patients into their subclasses on the basis of theirhormonal profile and physical examination. Study Design: Observational descriptive study.Setting: Biochemistry Department University of Health Sciences for Karyotyping and Geneticassessment, and its allied institution Biochemistry Department Quaid-e-Azam Medical CollegeBahawalpur for hormonal analysis, along with Pediatric Medicine Departments of Quaid-e-AzamMedical College / Bahawal Victoria Hospital Bahawalpur for collection of Sample and clinicalassessments. Period: June 2015 to December 2015. Study Design: Observational descriptivestudy. Material and Methods: 53 patients with 46, XY DSD were recruited. Complete clinicalhistory and data of each patient was recorded in the research proforma. Genitals examinedfor the phallus length and size, position of urinary meatus, palpation of gonads and shape ofthe labioscrotal folds. Ultrasonography examination of each patient was performed to look forundescended testes and for the presence of either male or female internal reproductive organs.Results: Base line levels of serum Testosterone Dihydrotestosterone Luteinizing hormone,Follicle stimulating hormone, 17-OH-Progesteron and Anti-mullerian hormones were measuredby ELISA technique. Testosterone and DHT were measured again after hCG stimulation. Onthe basis of physical examination, ultrasonographic findings and hormonal profile diagnosisof the types of 46, XY DSD was possible in 27 (51%) of patients. Androgen synthesis defect asa cause of 46, XY DSD was diagnosed in 7(13%) patients, Androgen insensitivity syndrome in6(11%) patients, 5-Alpha reductase deficiency in 3(6%) patients, Gonadal Dysgenesis in 3 (6%),Persistent Mullerian Duct Syndrome in 3(6%) and Isolated Hypospadias in 2 (4%) patients.There were 26 (49%) patients which remain undiagnosed with the algorithm of diagnosis usedin the present study.

Molecular Analysis of the AR and SRD5A2 Genes in Patients with 46,XY Disorders of Sex Development

2008 ◽  
Vol 21 (6) ◽  
pp. 545-554
Author(s):  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Eul-Ju Seo ◽  
Kun-Suk Kim ◽  
Sung Hoon Kim ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Dna Analysis ◽  
Disorders Of Sex Development ◽  
Plasma Renin ◽  
Serum Testosterone ◽  
Androgen Insensitivity Syndrome ◽  
Reference Ranges ◽  
Reductase Deficiency ◽  
Sex Development ◽  
Precise Diagnosis

Abstract The aim of this study was to assess the clinical and endocrinological features, and to analyze AR and SRD5A2 genes in patients with 46,XY disorders of sex development (DSD). This study included 20 patients from 19 families showing clinical features of 46,XY DSD. Molecular analysis was performed of the AR and SRD5A2 genes, as well as endocrinological evaluations, such as 17a-hydroxyprogesterone, plasma renin activity, aldosterone, adrenocorticotropic hormone and hCG stimulation test. Out of 20 patients with 46,XY DSD, only one (5%) displayed androgen insensitivity syndrome (AIS), and four (20%) were Sa-reductase deficient by mutation analysis. The patient with AIS revealed significant elevation of serum testosterone following hCG stimulation. The patient with Sa-reductase deficiency with a homozygous p.R246Q mutation had a low basal dihydrotestosterone level. The patient with p.Q6X/p.R246Q mutations showed a moderately elevated testosterone/ dihydrotestosterone ratio following hCG stimulation. Endocrinological tests are not reliable for the etiological diagnosis of AIS and Sa-reductase deficiency due to variable reference ranges of hormonal profiles according to the age and the severity of the enzyme defect. DNA analysis may be employed as a tool for the early and precise diagnosis of patients with 46,XY DSD, and genetic counseling can be used for families at risk.

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