Here, we show that a majority of patients with KLB mutations (9/13) exhibit hypogonadotropic hypogonadism with some degree of metabolic defect (i.e. overweight, insulin resistance, and/or dyslipidemia), consistent with the metabolic role of FGF21/KLB/FGFR1 pathway. The gene discussed is FGF21; the disease is Insulin resistance.