BackgroundWhile obesity is common in the United States, monogenic obesity is rare, accounting for approximately 5% of individuals with obesity. New targeted therapies for genetic forms of obesity are available but there is limited guidance on who requires testing. The aims of this study were to evaluate the prevalence of potentially clinically significant variants among individuals in Pediatric Endocrinology or Medical Weight Center clinics at a single center and to identify clinical characteristics that may make genetic obesity more likely.MethodsChildren and adults who had a genetic test for obesity, Uncovering Rare Obesity Gene panel, ordered during routine clinic visits from December 2019 to March 2021 were identified.ResultsOf the 139 patients with testing ordered, 117 had available results and clinical data. Over 40% (52/117, 44%) had at least one positive result (variant) with a variant that is considered pathogenic, likely pathogenic, or a variant of uncertain significance. No association was detected between age, sex, race, and body mass index (BMI) or BMI z‐score with a variant. Twenty‐six individuals (22%) had one or more variants in genes associated with Bardet Biedl Syndrome, and 8 (6.8%) of them had pathogenic variants, higher than expected.ConclusionOverall, clinical suspicion for genetic obesity is important in determining who requires genetic testing but no clinical factors were found to predict results. While obesity is multifactorial, novel medications for genetic forms of obesity indicate the need for evidence‐based guidelines for who requires genetic testing for obesity.
Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations in GNAS. This cross-sectional study investigated whether PHP patients with parathyroid hormone (PTH), thyrotropin (thyroid stimulating hormone; TSH), and free thyroxine (T4) levels at goal required higher doses of levothyroxine and calcitriol than recommended by current guidelines to overcome mineral ion abnormalities due to hormone resistance. Baseline demographic and clinical data of participants enrolled in PHP research studies between 2012-2021 were collected via retrospective chart review. Longitudinally, data were recorded at a maximum frequency of once a year starting at 1 year of age. The PTH at goal (PAG) group was defined as PTH < 150 pg/mL and calcium ≥ 8.4 mg/dL, and the TSH and free T4 at goal (TAG) group was defined as TSH < 5 mIU/L and free T4 ≥ 0.8 ng/dL. The PAG group (n = 74) was prescribed higher calcitriol doses than the PTH not at goal (PNAG) group (n = 50) (0.9 ± 1.1 vs 0.5 ± 0.9 mcg/day, P = 0.04) and 21% of individual patients were prescribed ≥ 1.5 mcg of calcitriol daily. This remained true after normalization for body weight (0.013 ± 0.015 vs 0.0067 ± 0.0095 mcg/kg/day, P = 0.008). There was no statistically significant difference in levothyroxine dosing between the TAG group (n = 122) and TSH and free T4 not at goal (TNAG) group (n = 45) when normalized for weight (2.0 ± 0.7 vs 1.8 ± 0.7 mcg/kg/day, P = 0.2). More than one-third of patients with PHP had PTH levels not at goal and some patients required calcitriol doses ≥ 1.5 mcg/day to meet current treatment goals.
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