Acquired Diseases that Replicate the Defect of Genetic Diseases

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 is just one example of phenocopy disease (from my book):

Acquired conduction defect [the phenocopy disease] and inherited conduction defect [the rare, genetic disease that is copied by the phenocopy disease]

Disorders of the electrical systems in humans that defects of ion flux across membranes are known as channelopathies. The inherited cardiac conduction channelopathies were discussed in Section 5.3.

Because the anti-arrhythmogenic and anti-epileptic drugs typically target ion channels, they are the drugs most likely to produce, as an adverse side effect, disorders of cardiac conduction. For example, rufinamide, an oral antiepileptic drug, has been reported to cause QT-interval shortening [44]. Quinidine, disopyramide, and procainamide have been reported to produce QT prolongation [45].

Several channelopathies can be acquired as autoimmune diseases, in which antibodies react with ion channels, or related cellular components upon which the ion channels depend (e.g., myasthenia gravis, Lambert–Eaton myasthenic syndrome, cerebellar ataxia associated with VGCC antibodies, acquired neuromyotonia, Morvan fibrillary chorea, limbic encephalitis) [46].

Progressive familial heart block type IA is a genetic disorder of the cardiac conduction system. Clinically similar conditions can be acquired when the tissues of the conduction systems are damaged, as in: myocardial infarct, conduction system ischemia (i.e., lack of blood flow to components of the conduction system, particularly the His–Purkinje conduction tissue), age-related degeneration of conduction system, and complications of procedures (i.e., insertion of wires or lines into the heart chambers) [47].

In a similar fashion, there are some types of cancer that can have a genetic cause or an environmental cause (or both). For example, most lung cancer occurring in humans has an an acquired, environmental cause (i.e., smoking). Some cases of lung cancers are genetic (i.e., inherited NUT gene mutation in midline lung carcinoma of the young). The importance of the phenocopy diseases (acquired near-equivalents of rare genetic diseases) to our general understanding of cancer, and to the successful treatment of rare cancers and common cancers, is discussed in my book.

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, heart block, arrhythmia, disease biology, cancer, carcinogenesis, acquired cancer, environmental cancer, rare cancer, common cancer