1283 ROLE OF EPIDERMAL GROWTH FACTOR IN THE PHENOTYPIC EXPRESSION OF LEPRECHAUNISM

Abstract

Epidermal growth factor (EGF) is a polypeptide hormone important in growth and differentiation of multiple cell types. It has a wide range of biological activities including precocious eruption of teeth, gut mucosa hyperplasia, and proliferation of epidermal cells in mice. Despite multiple known biological functions and presence in several body fluids, no disease state has been identified in which there is either a deficiency or excess of EGF. Leprechaunism (L) has many of the characteristics expected in EGF hypersecretion, i.e., severe acanthosis nigricans, hirsutism, pachyderma, precocious breast development and hypertrophy of gut and genitals. We have measured urinary EGF excretion in an 8-year-old patient with L over several years and found a mean concentration to be 151.9±50.4μg/gm cr. In comparison we have measured urinary EGF concentrations in normal children and children with various disease states. EGF excretion was linear with creatinine excretion and not influenced by age. The mean EGF excretion is 26.7±4.3μg/gm cr in control children as compared to 29.6±1.1 and 39.8±1.6μg/gm cr in normal adult males and females respectively. Blood EGF levels in our patient were increased above normal. Measurement of other gut hormones were normal. We conclude that many of the phenotypic manifestations of L are secondary to excessive EGF, thus providing a disease for this well characterized but otherwise orphan hormone.