In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.
Phenocopy diseases are medical conditions that closely mimic a genetic disease, but are caused or triggered by an environmental factor. In many cases, phenocopy diseases are non-hereditary and acute. In some cases, the phenocopy disease is reversible when the environmental trigger is removed or when an appropriate treatment is applied.
Here are two examples of phenocopy disease (from my book):
Acquired porphyria cutanea tarda [the phenocopy disease] and inherited porphyria cutanea tarda [the genetic form]The importance of the phenocopy diseases to our general understanding of disease processes, and to the development of successful treatments for rare diseases and common diseases, is discussed in Chapter 9.
The porphyrias are a group of disorders caused by deficiencies of enzymes involved in the synthesis of heme, a constituent of hemoglobin, p450 liver cytochromes, catalase, peroxidase, and myoglobin. Two tissues account for the bulk of heme synthesis in the body: erythropoietic cells and liver cells. All of the porphyrias are characterized by excessive production of porphyrin molecules. Porphyria cutanea tarda is caused by a deficiency of uroporphyrinogen decarboxylase, an enzyme involved in heme synthesis within liver cells. The disease is manifested as blistering and discoloration in sun-exposed areas of the skin. It is surmised that sunlight reacts with porphyrins to produce toxic oxygen radicals.
About 20% of the cases of porphyria cutanea tarda are inherited as a uroporphyrinogen decarboxylase deficiency. Many individuals with inherited deficiencies will never experience any of the skin manifestations of the disease (see Glossary item, Penetrance). Most of the remainder of cases of porphyria cutanea tarda are due to acquired liver damage, such as that produced by longterm alcohol production or hepatitis C infection. The damaged liver cells have a defective heme pathway leading to an excess of porphyrin.
Acquired von Willebrand disease [the phenocopy disease] and inherited von Willebrand disease [the genetic form]
Von Willebrand factor is a complex protein, the largest protein found in plasma, and is required for platelet adhesion. Reduction in von Willebrand factor results in a clotting disorder. Von Willebrand disease can result from inherited deficiency or it can be acquired through several mechanisms. In an autoimmune variant of the disease, antibodies reacting with the factor produce a protein complex that is rapidly cleared, effectively producing a deficiency. As a large, complex molecule, von Willebrand factor is particularly vulnerable to mechanical disruption. Artificial heart valves have been observed to produce von Willebrand disease. In cases of thrombocythemia (i.e., increased numbers of platelets in blood), excess platelets can absorb the von Willebrand factor to produce a functional deficiency.
I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.
- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, orphan disease, orphan drugs, phenocopy disease, complex disease, pathogenesis, mimic, epidemiology, disease etiology
