Krabbe disease

Krabbe disease
Classification and external resources
Specialty endocrinology
ICD-10 E75.2
ICD-9-CM 330.0
OMIM 245200
DiseasesDB 29468
MedlinePlus 001198
eMedicine ped/2892
MeSH D007965
GeneReviews

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 Krabbe (1885–1965).[2]

New York,[3] Missouri and Kentucky[4] include Krabbe in the newborn screening panel.[5]

Signs and symptoms

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,[6] blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. Juvenile- and adult-onset cases of Krabbe disease also occur, which have similar symptoms but slower progression.

Causes

Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31),[7] which causes a deficiency of an enzyme called galactosylceramidase.[8] 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.[9] Psychosine has been suggested to cause axonal degeneration in both the central and peripheral nervous systems by disrupting lipid rafts and may play a role in Krabbe disease.[10][11]

Diagnosis

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.

Treatment

Although no cure for Krabbe disease is known, 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. Cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.[12]

Prognosis

In infantile Krabbe disease, death usually occurs in early childhood. A 2011 study found 1, 2, 3 year survival rates of 60%, 26% and 14%, respectively. A few survived for longer and one was still alive at age 13. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.[13]

Epidemiology

Krabbe disease occurs in about one in 100,000 births.[14] A higher incidence, about six in 1,000,[14] has been reported in certain communities in Israel.[15] Scandinavian countries have comparatively high rates of the disease, reported to be one in 50,000 births.[16] Krabbe disease may also be found in cats[17] and in dogs, particularly Westies and Cairn Terriers.[18][19] The disease may also be found in dolphins.

Advocacy

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

References

  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. ↑ Duffner, Patricia K.; Caggana, Michele; Orsini, Joseph J.; Wenger, David A.; Patterson, Marc C.; Crosley, Carl J.; Kurtzberg, Joanne; Arnold, Georgianne L.; Escolar, Maria L. (2009-04-01). "Newborn Screening for Krabbe Disease: the New York State Model". Pediatric Neurology. 40 (4): 245–252. doi:10.1016/j.pediatrneurol.2008.11.010.
  4. ↑ (KRS 214.155)
  5. ↑ "unbs_state - Hunter's Hope Foundation". www.huntershope.org. Retrieved 2016-11-14.
  6. ↑ 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.
  7. ↑ Cannizzaro, L.A. (1994). "Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization". Cytogenetic and Genome Research. 66 (4): 244–245. doi:10.1159/000133703.
  8. ↑ "Krabbe disease". National Institutes of Health.
  9. ↑ Svennerholm, L.; Vanier, M. T.; Månsson, J. E. (1980-01-01). "Krabbe disease: a galactosylsphingosine (psychosine) lipidosis.". Journal of Lipid Research. 21 (1): 53–64. ISSN 0022-2275. PMID 7354254.
  10. ↑ 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. PMC 3278277Freely accessible. PMID 20410102.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Duffner, Patricia K.; Barczykowski, Amy; Jalal, Kabir; Yan, Li; Kay, Denise M.; Carter, Randy L. "Early Infantile Krabbe Disease: Results of the World-Wide Krabbe Registry". Pediatric Neurology. 45 (3): 141–148. doi:10.1016/j.pediatrneurol.2011.05.007.
  14. 1 2 "Krabbe disease". Genetics Home Reference. United States National Library of Medicine. 2008-05-02. Retrieved 2008-05-07.
  15. ↑ http://onlinelibrary.wiley.com/doi/10.1002/ajmg.1320210420/abstract
  16. ↑ Books.Google.com
  17. ↑ 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.
  18. ↑ NYtimes.com
  19. ↑ 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. doi:10.5414/npp27295. PMID 18808060.

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

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