A disease that affects fewer than five in 10,000 of the general population is defined as “rare”; however, due to the number of known rare diseases, the total number of individuals affected by rare diseases is relatively high. According to current estimates, in the USA alone, a rare disease directly affects about 25–30 million people. It is predicted that, in the majority of cases, the underlying cause is genetic in origin. With rare diseases that manifest in early childhood, it is likely that the cause of disease is related to the inheritance of genomic changes; therefore, performing molecular genetic analysis within these patients is of particular importance.
Facts and Numbers
There are 6,000–8,000 known rare diseases.
A total of 6%–7% of the population suffer from a rare disease.
80% are genetic; others are triggered by infections, allergies, or environmental influences.
75% of those affected are children, and 30% pass away before the age of five years old.
For physicians, rare diseases are a unique challenge. Often the diagnostic and therapeutic procedures are complex, and clinical routines are rarely standardized. This is particularly important when multiple organ systems are affected, and the expertise of professionals in many disciplines is required. Therefore, a good cooperation between the family physician, disease specialists, and scientific experts is essential for early diagnosis; however, for some patients who are suffering from a rare disease, there are currently no therapies available.
Molecular genetic confirmation of a suspected diagnosis often means the end to a year’s long odyssey in search of the cause of a medical condition. At the same time, it represents the starting point for more specific information about the progress and prognosis of the disease and for the optimal therapeutic intervention for the patient. Even if there is currently no known specific treatment available, knowledge of the etiology and mechanisms of disease can form the basis for a future treatment strategy or innovative treatment options. In addition, it provides information on the mode of inheritance and thus the probability of other family members inheriting the disease. This, therefore, gives concrete information regarding family planning and disease risk for current family members. An established diagnosis facilitates the reduction of bureaucratic obstacles, including applying for aids, rehabilitative, and nursing measures. It can also facilitate the communication with specialists, allowing for inclusion in clinical trials, support groups, access to specialized medical devices, or fast access to treatment options.
CeGaT and Rare Diseases
New technologies have enabled the simultaneous analysis of large amounts of genetic information for disease-causing changes. This technology is referred to as next-generation sequencing (NGS). CeGaT not only has the necessary up-to-date equipment but also a highly specialized team consisting of biologists, biochemists, bioinformatics, and human geneticists who interpret large quantities of data and evaluate results according to the current state of science.
For this analysis, our experts work closely with the referring clinicians. Where there are disease-related mutations, we consult with the clinician regarding further analysis, including analysis of additional family members or information regarding relevant studies.
Female, six months old
Congenital bone marrow failure, recurrent infections, anemia, dystrophy, reduced neutrophil and thrombocyte count
Brother with same symptoms passed away at the age of seven months
Initial Planned Therapy Strategy
Bone marrow transplantation
Chance of survival at about 50%
Results of Trio Exome Analysis
Defect in vitamin B12 metabolism (despite normal blood values)
No bone marrow transplantation; instead, high-dose therapy with vitamin B12 recommended
Using Trio Exome Analysis, the diagnosis was made within two weeks. The appointment for transplantation was cancelled, and the child developed normally following treatment.