The topic of phenocopy diseases was introduced in yesterday's blog post. 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 is just one example of phenocopy disease (from my book):
Acquired von Willebrand disease [the phenocopy disease] and inherited von Willebrand disease [the genetic disease]From observations of many phenocopy diseases, we can make the following generalization, discussed in Chapter 9 of my book:
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.9.5.1 Rule—Phenocopy diseases are typically mimics of rare diseases, not common diseases. Brief Rationale—The prototypical phenocopy disease involves a single agent having a specific effect on a single pathway in a limited number of cell types.In theory, any pathway can be altered by a drug to produce a phenotype that mimics a monogenic disease. A simple interruption of normal cellular function of a gene or a pathway is consistent with what we see in rare diseases and in phenocopy diseases, and lacks the cumulative acquisition of multiple genetic or cellular aberrations that typically characterize the common diseases. Phenocopy diseases provide important clues to the pathogenesis of rare and common diseases for the following reasons:1. There is usually one pathway involved, often found in a limited number of cell types, and the phenocopy disease teaches us how this pathway operates and how it can be disrupted.The phenocopy diseases help us to focus on the cellular pathways leading to disease. If you exclusively study the genetics of disease, you will likely miss the cellular pathways that link rare diseases with common diseases.
2. The pathway disrupted in the phenocopy disease is almost always the same pathway that is disrupted in the rare genetic disease. Hence, the phenocopy tells us how the rare disease expresses itself, and this is something that we can seldom infer from our knowledge of the gene mutation associated with the rare disease.
3. When the genetic cause of the rare disease is unknown, the careful study of its phenocopy will always yield a set of candidate genes that may operate in the rare disease.
4. Pharmacologic treatments for the phenocopy disease may apply to pathways operative in the genetic form of the disease or in the common diseases.
5. The pathway involved in a phenocopy disease can contribute to the pathogenesis of a common disease. Hence, understanding the phenocopy diseases brings us a little closer to understanding common diseases . This topic will be discussed further in Chapter 10.
6. Recognizing the cause of a phenocopy disease may curtail potential environmental catastrophes.
The phenocopy diseases remind us that you can have a disease without a causal gene, but you cannot have a disease without a causal pathway.
- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, orphan disease, orphan drugs, phenocopy disease, mimics of disease, principles of pathology, complex disease, disease biology, pathogenesis