Rare Disease Report


Rare Diseases in Genetics

Approximately 80% of rare diseases—the vast majority—possess a genetic etiology. Due to our care system structure, however, the primary point of intervention for patients who have rare diseases is usually their specialist’s office, not the geneticist’s. Increasingly, many of these specialists are becoming familiar with the numerous genetic tests, including newborn screening, that are available to aid diagnosis.

More than 7000 rare diseases are known to exist, with additional ones discovered every year. Gene-based rare conditions manifest in every system—and often in multiple systems—of the body.

A sampling includes:

  • Neurological: Batten disease, Charcot-Marie-Tooth disease, fragile X syndrome
  • Cardiologic: Brugada syndrome, familial hypercholesterolemia, familial hypertrophic cardiomyopathy, long QT syndrome
  • Endocrine: acromegaly, Addison’s disease, Cushing’s disease, phenylketonuria
  • Hematologic: sickle cell disease, hemophilia A and B, acute intermittent porphyria
  • Immune system dysfunctions: Evans syndrome, Graves’ disease
  • Cancer: parathyroid carcinoma, multiple myeloma, chronic myeloid leukemia
  • Metabolic disorders: Gaucher disease, Fabry disease
  • Diseases that impact multiple systems: megalocornea mental retardation syndrome, Pompe disease, Duchenne muscular dystrophy

Diagnostic Approach Emphasizes Early Detection

The severity associated with many genomic diseases, the crucial importance of clinical intervention, at the earliest possible opportunity, and the growing availability of newborn screening options, are among the primary reasons that the preponderance of gene-based disease detection initiatives focus on the infant population.

Progress in newborn screening for genetic disease represents one of the most significant public health advances of the last century. The World Health Organization advocates mandatory, free testing in all cases in which early diagnosis and treatment could benefit children.

The Recommended Uniform Screening Panel of the Advisory Committee on Heritable Disorders in Newborns and Children, under the purview of the US Department of Health and Human Services, functions as an advisory body regarding this public health matter, publishing reports and a regularly updated list of recommended screening procedures. In the United States, newborn screening protocols vary by state, although most states test for 40 to 50 conditions at birth.

In general, the testing process works as follows: potential positive tests are referred to geneticists for further evaluation. In New York state, for example, tests are evaluated in laboratories strategically distributed, for the sake of time-saving geographic convenience, throughout the state. If the presence of a disease is confirmed, the parents of the patient are notified. If time permits, this notification will be performed by the patient’s pediatrician so that the news can be broken by someone who has an established relationship with the family. If time is of the essence,
the referral center of the testing laboratory will call the parents directly to schedule immediate medical intervention.

Genetic counseling may also be employed for more subtle and/or complex cases. Genetic Counselors can calculate the risk of a rare genetic disease and help families choose the most appropriate genetic tests necessary to obtain a diagnosis.

At-risk patients also have the option of purchasing and ordering their own genetic tests from private companies, although the tests are not available on a direct-to-consumer basis. The patient sends a blood sample to a laboratory, and results are sent to a healthcare provider, usually the patient’s own physician or genetic counselor.

Online Resources

Newborn screening resources:
Genetic counseling:
List of rare conditions:
List of FDA-approved orphan drugs:

Treatment Options Increasing

For treatable genetic conditions, newborn screening is a game-changing life saver. For about 95% of rare diseases, however, not one FDA-approved treatment exists. That is not to suggest that genetic testing, even later in life, is without its use. In many cases, an accurate diagnosis of a disease can enable a patient to pursue strategies to mitigate symptom severity and enhance quality of life. An additional consideration: compared with the pre-genomic age, medical innovations are occurring at a far more accelerated pace. Today’s untreatable gene-based diseases may be treatable tomorrow.

A partial list of new agents, indications, and combinations recently approved by the FDA for the treatment of rare gene-based disease includes:

  • Cystic fibrosis: lumacaftor/ivacaftor (Orkambi), July 2015
  • Multiple myeloma: karfilzomib/lenalidomide/dexamethasone (Kyprolis/Revlimid/KRd), July 2015; panobinostat (Farydak), February 2015; and lenalidomide/dexamethasone (Revlimid/ Decadron), February 2015
  • Neuroblastoma: dinutuximab (Unituxin), March 2015
  • Papillary thyroid cancer: lenvatinib (Lenvima), February 2015
  • Hypoparathyroidism: parathyroid hormone (Natpara), January 2015
  • Waldenstrom’s macroglobulinemia: ibrutinib (Imbruvica), January 2015

Clinical Trials

Research into potential gene-based therapies is progressing at an unprecedented rate. A sampling of late-stage clinical trials currently underway includes:

  • Charcot-Marie-Tooth disease: PXT-3003
  • Cystic fibrosis: ataluren
  • Essential thrombocythemia: anagrelide retard, anagrelide hydrochloride
  • Gaucher disease: miglustat, velaglucerase alfa, taliglucerase alfa, eliglustat tartrate, imiglucerase
  • Hemoglobinuria: eculizumab
  • Huntington’s disease: latrepirdine, riluzole, coenzyme Q10, resveratrol, minocycline

Advocacy Support and Information

Rare disease advocacy groups—several are listed below—represent a valuable source of support and information:
Ben’s Friends, a patient support community:

Global Genes:

National (UK) Information Center for Metabolic Diseases:

National Organization for Rare Disorders:

Rare Diseases Clinical Research Network:

For comprehensive list, consult Appendix B of this resource guide.
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