Cole disease, also known as guttate hypopigmentation and punctate palmoplantar keratoderma with or without ectopic calcification, is a very rare disorder characterized by hypopigmented macules that typically affect the arms and legs and a punctate palmoplantar keratoderma. Both manifestations are present at birth or develop within the first year of life. Some patients with Cole disease develop calcifications within tendons, skin, or breast tissue.

Cole disease results from mutations in the gene ENPP1. Functions of the ENPP1 protein include breaking down extracellular ATP into AMP and pyrophosphate, which is crucial to prevent calcification and mineralization, and assisting in cell signaling in response to insulin, which helps regulate and control transport of melanin from the melanocytes to keratinocytes.

In most cases, Cole disease is inherited in an autosomal dominant pattern, but de novo mutations also occur. The prevalence of Cole disease is unknown; only a few case studies have been reported in the literature.

For more information, see OMIM.