Diagnosis of 5α-reductase 2 deficiency: is measurement of dihydrotestosterone essential?
| Autor: | Teresa Kam Chi Tsui, YY Lam, Ching Yin Lee, C C Shek, Betty Wai Man But, Almen Lai Na Lam, Angel O.K. Chan, Joanna Yuet Ling Tung, Wing Yee Tse, Pik To Cheung, Kwok Leung Ng, Yuk Kit Chan, Elaine Yin Wah Kwan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Pathology Adolescent Urinary system Clinical Biochemistry DNA Mutational Analysis Genetic analysis Gas Chromatography-Mass Spectrometry Young Adult 3-Oxo-5-alpha-Steroid 4-Dehydrogenase Internal medicine medicine Humans Disorders of sex development Young adult Child Retrospective Studies Disorder of Sex Development 46 XY business.industry Biochemistry (medical) Infant Membrane Proteins Retrospective cohort study Dihydrotestosterone medicine.disease SRD5A2 Child Preschool business Algorithms medicine.drug |
| Zdroj: | Clinical chemistry. 59(5) |
| ISSN: | 1530-8561 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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