There have been 590 cases in total. Currently there are 350 people living with this condition worldwide.
Familial Dysautonomia, is the result of mutations in IKBKAP gene on chromosome 9, which encodes for the IKAP protein (IkB kinase complex associated protein). There have been three mutations in IKBKAP identified in individuals with FD. The most common FD-causing mutation occurs in intron 20 of the donor gene. Conversion of T-->C in intron 20 of the donor gene resulted in shift splicing that generates an IKAP transcript lacking exon 20. Translation of this mRNA results in a truncated protein lacking all of the amino acids encoded in exons 20-37. Another less common mutation is a G-->C conversion resulting in one amino acid mutation in 696, where Proline substitutes normal Arginine. The decreased amount of functional IKAP protein in cells causes Familial Dysautonomia.
Symptoms displayed by a baby with FD might include:
Symptoms in an older child with FD might include:
A clinical diagnosis of FD is supported by a constellation of criteria:
Familial Dysautonomia is inherited in an autosomal recessive pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by generic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by amniocentesis (for 14-17 weeks) or chorionic villus sampling (for 10-11 weeks) is possible.
The survival rate and quality of life has increased since the mid 80's mostly due to greater understanding of the most dangerous symptoms. At present, FD patients can be expected to function independently if treatment is begun early and major disabilities avoided.
A major issue has been Aspiration Pneumonias, where food or regurgitated stomach content would be aspirated into the lungs causing infections. Fundoplacations (by preventing regurgitation) and gastrostomy tubes (to provide non oral nutrition) have reduced the frequency of hospitalization.
Other issues which can be treated include FD Crises, Scoliosis, and various eye conditions due to limited or no tears.
An FD crisis is the body's loss of control of various Autonomic nervous system functions including blood pressure, heartrate, and body temperature. Both short term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.
Although the FD-causing gene has been identified and it seems to have tissue specific expression, there is no definitive treatment at present. Treatment of FD remains preventative, symptomatic and supportive. FD does not express itself in a consistent manner. The type and severity of symptoms displayed vary among patients and even at different ages on the same patients. So patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and blood pressure. There are some commonly needed treatments including:
It is noted that in cell lines derived from heterozygous carriers of FD who display a normal phenotype, there are decreased levels of the wild-type IKAP transcript and also functional IKAP protein respectively. This would suggest that increasing the amount of the wild-type IKAP transcript may improve the manifestation in patients with FD. Application of tocotrienols in the treatment of FD was initiated in the FD research lab at Fordham University in Bronx. In vitro supplementation of tocotrienols elevated the expression of IKAP transcripts as well as the amount of induced functional IKAP protein in homozygous cell lines derived from FD patients. This observed result further suggests the value of therapeutic approaches to lessen suffered symptoms of FD patients by elevating cellular level of functional IKAP which can be induced by tocotrienols.
One form of therapy under investigation is electrolyte therapy for refractory seizures common among FD carriers, such as the product Ceralyte.
The outlook for patients with FD depends on the particular diagnostic category. Patients with chronic, progressive, generalized dysautonomia in the setting of central nervous system degeneration have a generally poor long-term prognosis. Death can occur from pneumonia, acute respiratory failure, or sudden cardiopulmonary arrest in such patients. Educate parents and patients regarding daily eye care and early warning signs of corneal problems as well as use of punctual cautery. This education has resulted in decreased corneal scarring and need for more aggressive surgical measures such as tarsorrhaphy, conjunctival flaps, and corneal transplants.
Despite that it probably would not happen in the near future, some expect that stem-cell therapy will result. Eventually, treatment could be given in utero.
While that may be years ahead, genetic screening became available around April 2001, enabling Ashkenazi Jews to find out if they are carriers. Screening organization Dor Yeshorim offers testing as part of its panel, which also includes Tay-Sachs disease and cystic fibrosis.
In the mean time more research into treatments are being funded by the foundations that exist. These foundation are organized and run by parents of those with FD. There is very limited governmental support beyond recognizing those diagnosed with FD as eligible for certain programs.