Diagnosis of 5α-reductase 2 deficiency: is measurement of dihydrotestosterone essential?

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 5ß-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.

Risk factors for post-operative complications in Chinese children with tonsillectomy and adenoidectomy for obstructive sleep apnea syndrome.

PURPOSE: Tonsillectomy and adenoidectomy (T&A) is commonly performed in children with obstructive apnea syndrome (OSAS). It was our hospital practice to observe all patients post T&A in the pediatric intensive care unit. We aim to describe the post-operative complications after tonsillectomy and adenoidectomy in children with OSAS and to identify risk factors for these complications. METHOD: Medical records of patients from 1 to 16 years old with OSAS and T&A done in this department were retrieved for analysis from April 1999 to July 2006. Information of the individual patients including the demographic data, polysomnography data, and presence of post-operative complications were recorded and analyzed. RESULTS: A total of 86 patient records were analyzed (M/F = 69:17). The mean BMI z score was 1.13 ± 1.53, and 36% of patients were classified as obese with z > 1.96. The median apnea-hypopnea index (AHI) before T&A was 9.8 episodes/h. Only six patients had post-operative desaturation. No bleeding complications were reported in our cohort. It was found that patients with desaturation after T&A had significantly higher mean BMI z score than children without desaturation (p = 0.014). There was otherwise no significant difference between the age, sex, AHI score, and the history of allergic rhinitis or asthma between the two groups. CONCLUSION: Our results showed that most children with OSAS underwent T&A without complications. The respiratory complication rate was 7%, and desaturation was the most common post-operative complication. Children with higher BMI z score were more likely to have desaturation after T&A (p = 0.014). Hence, careful monitoring with pulse oximeter after T&A should be offered to those who are obese.

The correlation among obesity, apnea-hypopnea index, and tonsil size in children.

BACKGROUND: The correlation between obesity and severity of obstructive sleep apnea (OSA) is well established in adults, but data are inconsistent in children. We hypothesized that there is a significant correlation between the degree of obesity and the severity of OSA in children. METHODS: We retrospectively reviewed records of weight, height, history, and polysomnography of all 1- to 15- year-old children referred to our sleep laboratory. Children with known anomalies and repeated polysomnography were excluded from this study. Obesity was defined as body mass index z score (BMI Z score) > 1.96. The correlation between BMI Z score and apnea-hypopnea index (AHI) was assessed. Possible confounding factors, ie, age, gender, and tonsil size, were adjusted by multiple linear regression. RESULTS: Four hundred eighty-two children were included in this study. Obese children had a significantly higher AHI (median, 1.5; interquartile range [IQR], 0.2 to 7.0) than the AHI of nonobese children (median, 0.7; IQR, 0.0 to 2.5). BMI Z score was significantly correlated with log-transformed AHI (Ln[AHI]) [r = 0.156, p = 0.003]. BMI Z score and tonsil size were still correlated with Ln(AHI) even after adjusted for other confounding factors (p = 0.001). CONCLUSION: Degree of obesity as measured by BMI Z score and tonsil size are significantly related to severity of OSA as reflected by the AHI, although the correlation is mild.