Hereditary sensory and autonomic neuropathy type 3 (Familial Dysautonomia)

Overview

Hereditary sensory and autonomic neuropathy type 3, also called familial dysautonomia, is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.

Symptoms

Symptoms are present at birth and grow worse over time:

  • Breath holding spells (can lose consciousness)
  • Constipation
  • Decreased taste
  • Diarrhea
  • Dry eyes
  • Feeding difficulties
  • Inability to feel pain and changes in temperature (can lead to injuries)
  • Long episodes of vomiting
  • Poor coordination - unsteady walk
  • Poor growth
  • Repeated fevers
  • Repeated pneumonia
  • Seizures
  • Skin blotching
  • Sweating while eating
  • Unusually smooth, pale tongue surface

Causes

Hereditary sensory and autonomic neuropathy type 3 is passed down through families (inherited).

Mutations in the IKBKAP gene cause familial dysautonomia.

The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.

Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP gene mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is pieced together to make a blueprint for the production of IKAP protein. As a result of this error, a reduced amount of normal IKAP protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia.

Prevention

People who are of an Eastern European Jewish background and families with a history of Riley-Day syndrome who are thinking of having children can seek genetic counseling to discuss their risk and undergo testing, when appropriate. Genetic testing by DNA is very accurate for Riley-Day syndrome. It may be used for diagnosing affected individuals, detecting carriers, and prenatal diagnosis.

Diagnosis

The health care provider will perform a physical exam. The patient may have:

  • Absent or decreased deep tendon reflexes
  • Lack of a response after receiving a histamine injection (normally redness and swelling would occur)
  • Lack of tears with emotional crying * Low muscle tone (hypotonia), especially in babies
  • Repeated episodes of high blood pressure
  • Severe scoliosis
  • Tiny pupils after receiving certain eye drops

Blood tests are available to check for the IKBKAP gene. The detection rate in the Ashkenazi Jewish population is greater than 99%.

Prognosis

With advances in diagnosis and treatment, survival continues to improve. Currently, a newborn with Riley-Day has a 50% chance of reaching age 30.

Treatment

Treatment may include:

  • Anticonvulsant therapy if there are seizures
  • Feeding in an upright position and giving textured formula to prevent gastroesophageal reflux
  • Increased fluid and salt intake, caffeine, and elastic stockings to prevent low blood pressure when standing (postural hypotension) 
  • Medicines called anti-emetics, to control vomiting
  • Medicines, including liquid tears, to prevent dry eyes
  • Physical therapy of the chest
  • Protecting the person from injury
  • Providing enough nutrition and fluids
  • Surgery or spinal fusion
  • Treating aspiration pneumonia

Resources

Call your doctor if symptoms change or get worse. A genetic counselor can help clarify information about the condition and tell you how to contact support groups in your area.