title: Diagnosis of 5α-reductase 2 deficiency: is measurement of dihydrotestosterone essential?
abstract: BACKGROUND
  5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD.
  
  
  METHODS
  We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years.
  
  
  RESULTS
  Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically.
  
  
  CONCLUSIONS
  5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.
authors.affiliation: Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong SAR. cok436@ha.org.hk
authors.forename: Angel On Kei
authors.initials: AO
authors.lastname: Chan
authors.forename: Betty Wai Man
authors.initials: BW
authors.lastname: But
authors.forename: Ching Yin
authors.initials: CY
authors.lastname: Lee
authors.forename: Yuen Yu
authors.initials: YY
authors.lastname: Lam
authors.forename: Kwok Leung
authors.initials: KL
authors.lastname: Ng
authors.forename: Joanna Yuet Ling
authors.initials: JY
authors.lastname: Tung
authors.forename: Elaine Yin Wah
authors.initials: EY
authors.lastname: Kwan
authors.forename: Yuk Kit
authors.initials: YK
authors.lastname: Chan
authors.forename: Teresa Kam Chi
authors.initials: TK
authors.lastname: Tsui
authors.forename: Almen Lai Na
authors.initials: AL
authors.lastname: Lam
authors.forename: Wing Yee
authors.initials: WY
authors.lastname: Tse
authors.forename: Pik To
authors.initials: PT
authors.lastname: Cheung
authors.forename: Chi Chung
authors.initials: CC
authors.lastname: Shek
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D013196:Dihydrotestosterone / Q000652:urine*; D058490:Disorder of Sex Development, 46,XY / Q000201:enzymology* / Q000235:genetics / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D013196:Dihydrotestosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human