Based on the impact of the leptin gene variants on leptin production and secretion and leptin receptor binding and activation, we define 3 subtypes of CLD: classical hormone deficiency due to defects in leptin synthesis and/or secretion, biological inactive hormone due to defects in leptin receptor binding, and antagonistic hormone due to defects in leptin receptor activation. The gene discussed is LEPR; the disease is congenital secretory chloride diarrhea 1.