MED-PED: An Integrated Genetic Strategy for Preventing Early Deaths

Abstract

New opportunities are emerging for preventing the consequences of serious diseases because of the discovery of causal mutations in specific gene loci. MED PED is an international collaboration to Make Early Diagnoses and Prevent Early Deaths in MEDical PEDigres.

The initial target of this effort is heterozygous familial hypercholesterolemia (FH).This is one of the most common and best understood serious single gene disorders. Clinical and genetic diagnoses are reliable, relatively inexpensive, and available worldwide. Potent and effective medications are available that act specifically at the site of genetically defective low density lipoprotein receptors. Clinical trials have established the ability of medical therapy to normalize cholesterol levels, arrest or reverse atherosclerotic coronary artery lesions, and significantly reduce morbidity and mortality.

Over 10 million persons in the world have FH and about 200,000 of them die with premature ischemic heart disease each year. Unfortunately few patients with FH are receiving the benefit of recent advances in the diagnosis and treatment of FH. Pooled estimates from 14 countries indicate that 80% of the patients with FH are not diagnosed, 84% are taking no medication to lower their cholesterol, and only 7% have reasonably well treated cholesterol levels. Moreover, few are adequately evaluated to detect and treat already established coronary artery disease.

The international MED-PED collaborators have organized to share successful approaches and combine efforts to find and help persons with FH. The initial computer registries in 14 countries contain 13,118 FH patients together with their relatives and physicians. Four international MED-PED subcommittees have been organized to focus on specific efforts:

• 1) Patient and Physician Education: to share educational materials and support programs

• 2) Government Affairs and Publicity: to increase public awareness and funding

• 3) Research and Molecular Genetics: to promote collaboration & research progress

• 4) Computer Data Management: to standardize tools for FH family registry data

A major feature of the MED-PED approach is concentration on high risk families for rapid case finding. From each known index case in the registry, several new FH cases can be identified among close relatives; sometimes many FH cases can also be found among distant relatives identified using pedigree expansion. Education, treatment, and long term support are also thought to be more effective in families. The MED-PED approach has been tested in some locations for up to six years with considerable success. The MED-PED model is also appropriate for other treatable dominant single gene diseases such as familial defective Apo B, dominant Type III hyperlipidemia, glucocortoid remediable aldosteronism (GRA) with hypertension and early strokes, long QT sudden arrhythmic death syndrome, and some forms of breast and colon cancer.