title: Current treatments in familial dysautonomia.
abstract: BACKGROUND
  Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (type III). The disease is caused by a point mutation in the IKBKAP gene that affects the splicing of the elongator-1 protein (ELP-1) (also known as IKAP). Patients have dramatic blood pressure instability due to baroreflex failure, chronic kidney disease, and impaired swallowing leading to recurrent aspiration pneumonia, which results in chronic lung disease. Diminished pain and temperature perception result in neuropathic joints and thermal injuries. Impaired proprioception leads to gait ataxia. Optic neuropathy and corneal opacities lead to progressive visual loss.
  
  
  METHODS
  This article reviews current therapeutic strategies for the symptomatic treatment of FD, as well as the potential of new gene-modifying agents.
  
  
  CONCLUSIONS
  Therapeutic focus on FD is centered on reducing the catecholamine surges caused by baroreflex failure. Managing neurogenic dysphagia with effective protection of the airway passages and prompt treatment of aspiration pneumonias is necessary to prevent respiratory failure. Sedative medications should be used cautiously due to the risk of respiratory depression. Non-invasive ventilation during sleep effectively manages apneas and prevents hypercapnia. Clinical trials of compounds that increase levels of IKAP (ELP-1) are underway and will determine whether they can reverse or slow disease progression.
authors.affiliation: New York University School of Medicine, Dysautonomia Center, Department of Neurology , 530 First Avenue, Suite 9Q New York, NY 10016 , USA +1 212 263 7225 ; Horacio.Kaufmann@nyumc.org.
authors.forename: Jose-Alberto
authors.initials: JA
authors.lastname: Palma
authors.forename: Lucy
authors.initials: L
authors.lastname: Norcliffe-Kaufmann
authors.forename: Cristina
authors.initials: C
authors.lastname: Fuente-Mora
authors.forename: Leila
authors.initials: L
authors.lastname: Percival
authors.forename: Carlos
authors.initials: C
authors.lastname: Mendoza-Santiesteban
authors.forename: Horacio
authors.initials: H
authors.lastname: Kaufmann
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015259:Dopamine Agents / Q000627:therapeutic use; D004402:Dysautonomia, Familial / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D005128:Eye Diseases / Q000150:complications / Q000188:drug therapy; D005767:Gastrointestinal Diseases / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy; D035602:Transcriptional Elongation Factors; D014570:Urologic Diseases / Q000150:complications / Q000188:drug therapy
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D002352:Carrier Proteins; D015259:Dopamine Agents; C114720:Elp1 protein, human; D035602:Transcriptional Elongation Factors
keywords: future directions; hereditary autonomic neuropathy; hypertensive surges; nausea; splicing modification therapy