Angela Qiu Krabbe Disease

What is galactocerebroside beta-galactosidase? Krabbe disease causes not enough of it to be made Not enough myelin made Material that protects and surrounds nerve fibers Made up of protein and fatty substances Main purpose is for fast and efficient transmission of impulses Dugdale, David C. Myelin. Ed. David Zieve. National Institute of Health, 21 May 2009. Web. 7 Mar. 2011. <http://www.nlm.nih.gov/medlineplus/ency/article/002261.htm>.

Galactocerebroside beta-galactosidase (continued) Myelin is constantly built and broken down as nerves grow Enzymes are needed to break it down Galactosylceramidase enzyme also becomes less effective Psychosine accumulates in the cell Too much is toxic Damages myelin producing cells Narins, Brigham, ed. The Gale Encyclopedia of Genetic Disorders. 2nd ed. Vol. 1. Farmington Hills: Thomson Gale, 2005. 722-24. 2 vols. Print.

Galactocerebroside beta-galactosidase (continued) Un-metabolized substances accumulate in large globoid cells Also called globoid cell leukodystrophy Section of brain with Krabbe disease Globoid cells around blood vessels (blue arrows) 1. Wynbrandt, James, and Mark D. Ludman. Genetic Disorders and Birth Defects. 2nd ed. New York: Facts on File, 1991. 193-94. Print. 2. “Leukodystrophies.” UCSF. 6 Mar. 2011 <http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Leukodystrophies.htm>

Pattern of Inheritance autosomal =female /male carrier =affected with Krabbe disease R r RR Rr rr R = normal r = Krabbe Disease Pedigree recessive Punnett Square

Location of the gene Located on the GALC gene Chromosome number 14 “Galactosylceramidase” is the official name Chromosome number 14 Located on base pair numbers 88,399,357 to 88,459,906 1. GALC. National Institute of Health, 1 Mar. 2007. Web. 7 Mar. 2011. <http://ghr.nlm.nih.gov/gene/GALC>. 2. “GALC.” Digital. National Institute of Health. 6 Mar. 2011. <http://ghr.nlm.nih.gov/dynamicImages/chromomap/GALC.jpeg>

Sequence of the mutation More than seventy mutations can cause Krabbe Disease Most common mutation deletes a large segment of the GALC gene 30-kb del Usually found in those of European & Mexican descent Late-onset form Usually has mutation G270D or G809A in one of the two copies of the gene The other copy usually has a different mutation, like the 30-kb del The G270D/ G809A allows for some myelin to be made for some time, so onset of the disease is delayed GALC. National Institute of Health, 1 Mar. 2007. Web. 7 Mar. 2011. <http://ghr.nlm.nih.gov/gene/GALC>. Wenger, David A. Krabbe Disease. 19 June 2000. Web. 4 Mar. 2011. <http://www.ncbi.nlm.nih.gov/books/NBK1238/>.

beta-galactosidase People who have Krabbe disease can’t make enough of this to produce enough myelin. “Beta-galactosidase.” Computer generated. UniProt. UCSC Genome Bioinformatics. 7 Mar. 2011. <http://genome.ucsc.edu/cgi-bin/hgGene?db=mm9&hgg_gene=uc007olf.1&hgg_chrom=none>

Symptoms! Affects the nervous system Average person dies at 13 months Early-onset (85-90% of the time) Changing muscle tone from floppy to rigid Hearing loss Feeding difficulties Random fevers Usually dies before age of 2 Late-onset Not as severe, more likely to live longer Symptoms vary from person to person Walking difficulties Vision problems Rigid muscles Krabbe Disease. Ed. Chad Haldeman-Englert and David Zieve. National Institute of Health, 15 Apr. 2009. Web. 7 Mar. 2011. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH 0002178/>.

Cures or Treatments No specific treatment available Bone marrow transplants may work, but there are some risks Studies show that umbilical cord blood stem cell transplants were successful Physical therapy can also help Gene therapy Introduce normal GALC gene into cells Still in research stages, not performed clinically Narins, Brigham, ed. The Gale Encyclopedia of Genetic Disorders. 2nd ed. Vol. 1. Farmington Hills: Thomson Gale, 2005. 722-24. 2 vols. Print.

History Probably originated in Sweden First described in 1916 by Danish neurologist Knud Haraldsen Krabbe Observed the condition in two siblings Described the globoid cells in the white matter of the brain Wynbrandt, James, and Mark D. Ludman. Genetic Disorders and Birth Defects. 2nd ed. New York: Facts on File, 1991. 193-94. Print.

Other Info No cases have been reported in the Ashkenazi Jewish population ~1 in 100,000 infants born in the US & Europe will have Krabbe disease A Druze community in Northern Israel and two Moselm Arab villages near Jerusalem have an unusually high incidence rate One in every six people is a carrier Wenger, David A. Krabbe Disease. National Institute of Health, 19 June 2000. Web. 4 Mar. 2011. <http://www.ncbi.nlm.nih.gov/books/NBK1238/>.

Bibliography “Beta-galactosidase.” Computer generated. UniProt. UCSC Genome Bioinformatics. Web. 7 Mar. 2011. <http://genome.ucsc.edu/cgi-bin/hgGene?db=mm9&hgg_gene=uc007olf.1&hgg_chrom=none> Dugdale, David C. Myelin. Ed. David Zieve. National Institute of Health, 21 May 2009. Web. 7 Mar. 2011. <http://www.nlm.nih.gov/medlineplus/ency/article/002261.htm>. GALC. National Institute of Health, 1 Mar. 2007. Web. 7 Mar. 2011. <http://ghr.nlm.nih.gov/gene/GALC>. “GALC.” Digital. National Institute of Health. Web. 6 Mar. 2011. <http://ghr.nlm.nih.gov/dynamicImages/chromomap/GALC.jpeg> Krabbe Disease. Ed. Chad Haldeman-Englert and David Zieve. National Institute of Health, 15 Apr. 2009. Web. 7 Mar. 2011. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH 0002178/>.

Bibliography (cont.) Krabbe Disease. National Institute of Health, 27 Oct. 2010. Web. 7 Mar. 2011. <http://www.ninds.nih.gov/disorders/krabbe/krabbe.htm>. “Leukodystrophies.” UCSF. Web. 6 Mar. 2011 <http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Leukodystrophies.htm> Narins, Brigham, ed. The Gale Encyclopedia of Genetic Disorders. 2nd ed. Vol. 1. Farmington Hills: Thomson Gale, 2005. 722-24. 2 vols. Print. Wenger, David A. Krabbe Disease. National Institute of Health, 19 June 2000. Web. 4 Mar. 2011. <http://www.ncbi.nlm.nih.gov/books/NBK1238/>. Wynbrandt, James, and Mark D. Ludman. Genetic Disorders and Birth Defects. 2nd ed. New York: Facts on File, 1991. 193-94. Print.

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