Krabbe disease

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Krabbe disease
Classification and external resources
ICD-10 E75.2
ICD-9 330.0
OMIM 245200
DiseasesDB 29468
MedlinePlus 001198
eMedicine ped/2892
MeSH D007965

Krabbe disease (also known as globoid cell leukodystrophy[1] or galactosylceramide lipidosis) is a rare, often fatal degenerative disorder that affects the myelin sheath of the nervous system. It is a form of sphingolipidosis, as it involves dysfunctional metabolism of sphingolipids. This condition is inherited in an autosomal recessive pattern. The disease is named after the Danish neurologist Knud Haraldsen Krabbe (1885-1965).[2]

Incidence[edit]

Krabbe disease occurs in about 1 in 100,000 births.[3] A higher incidence, about 6 in 1,000,[3] has been reported in Israel.[4] Scandinavian countries have comparatively high rates of the disease, reported to be 1 in 50,000 births.[5] Krabbe disease may also be found in cats[6] and in dogs, particularly Westies and Cairn Terriers.[7][8]

Causes[edit]

Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31),[9] which causes a deficiency of an enzyme called galactosylceramidase[10]. In rare cases it may be caused by a lack of active saposin A.

The build-up of unmetabolized lipids affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerves) and causes severe degeneration of motor skills. As part of a group of disorders known as leukodystrophies, Krabbe disease results from the imperfect growth and development of myelin.

GALC deficiency also results in a build-up of a glycosphingolipid called Psychosine. It has been suggested Psychosine causes axonal degeneration in both the CNS and PNS by disrupting lipid rafts and may play a role in Krabbe disease.[11][12]

Symptoms[edit]

Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement,[13] blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression.

Diagnosis[edit]

The disease may be diagnosed by its characteristic grouping of certain cells (multinucleated globoid cells), nerve demyelination and degeneration, and destruction of brain cells. Special stains for myelin (e.g.; luxol fast blue) may be used to aid diagnosis.

Prognosis[edit]

In infants, the disease is generally fatal before age 2. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.

Treatment[edit]

Although there is no cure for Krabbe disease, bone marrow transplantation has been shown to benefit cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy may help maintain or increase muscle tone and circulation. A recent study in the New England Journal of Medicine reports that cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.[14]

Advocacy[edit]

Former Buffalo Bills quarterback Jim Kelly has been a leader in gaining recognition and research funding for Krabbe disease, following the diagnosis of his son, Hunter, in 1997. Hunter Kelly died of the disease on August 5, 2005, at the age of 8.

See also[edit]

References[edit]

  1. ^ Lee WC, Tsoi YK, Troendle FJ, et al (August 2007). "Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy". FASEB J. 21 (10): 2520–7. doi:10.1096/fj.06-6169com. PMID 17403939. 
  2. ^ synd/1457 at Who Named It?
  3. ^ a b "Krabbe disease". Genetics Home Reference. United States National Library of Medicine. 2008-05-02. Retrieved 2008-05-07. 
  4. ^ http://onlinelibrary.wiley.com/doi/10.1002/ajmg.1320210420/abstract
  5. ^ Books.Google.com
  6. ^ Salvadori C, Modenato M, Corlazzoli DS, Arispici M, Cantile C (May 2005). "Clinicopathological features of globoid cell leucodystrophy in cats". J. Comp. Pathol. 132 (4): 350–6. doi:10.1016/j.jcpa.2004.12.001. PMID 15893994. 
  7. ^ NYtimes.com
  8. ^ Capucchio MT, Prunotto M, Lotti D, Valazza A, Galloni M, Dore B, Pregel P, Amedeo S, Catalano D, Cornaglia E, Schiffer D (2008). "Krabbe's disease in two West Highland White terriers". Clin. Neuropathol. 27 (5): 295–301. PMID 18808060. 
  9. ^ "Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization". doi:10.1159/000133703. 
  10. ^ http://ghr.nlm.nih.gov/condition/krabbe-disease.  Missing or empty |title= (help)
  11. ^ Lee, Wing; Kang, Dongcheul; Causevic, Ena; Herdt, Aimee; Eckman, Elizabeth; Eckman, Christopher (2010). "Molecular Characterization of Mutations That Cause Globoid Cell Leukodystrophy and Pharmacological Rescue Using Small Molecule Chemical Chaperones". The Journal of Neuroscience 30 (16): 5489–5497. doi:10.1523/JNEUROSCI.6383-09.2010. PMID 20410102. 
  12. ^ White, Adam; Givogri, Maria; Lopez-Rosas, Aurora; Cao, Hongmei; Breemen, Richard van; Thinakaran, Gopal; Bongarzone, Ernesto (2009). "Psychosine Accumulates in Membrane Microdomains in the Brain of Krabbe Patients, Disrupting the Raft Architecture". The Journal of Neuroscience 29 (19): 6068–6077. doi:10.1523/JNEUROSCI.5597-08.2009. PMID 19439584. 
  13. ^ Hussain, S. A.; Zimmerman, H. H.; Abdul-Rahman, O. A.; Hussaini, S. M.; Parker, C. C.; Khan, M. (May 2011). "Optic Nerve Enlargement in Krabbe Disease: A Pathophysiologic and Clinical Perspective". Journal of Child Neurology 26 (5): 642–644. doi:10.1177/0883073810387929. PMID 21285037.  edit
  14. ^ Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J (2005). "Transplantation of Umbilical-Cord Blood in Babies with Infantile Krabbe's Disease". New England Journal of Medicine 352 (20): 2069–2081. doi:10.1056/NEJMoa042604. ISSN 0028-4793. OCLC 206940639. PMID 15901860. BL Shelfmark 6084.000000. 

This article incorporates public domain text from the United States National Library of Medicine and the National Institute of Neurological Disorders and Stroke.

External links[edit]