KRABBE DISEASEAngela Qiu

What is galactocerebroside beta-galactosidase?

Krabbe disease causes not enough of it to be made

Not enough myelin madeMaterial that protects and surrounds

nerve fibersMade up of protein and fatty

substancesMain 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 growEnzymes are needed to break it down

Galactosylceramidase enzyme also becomes less effectivePsychosine 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 cellsAlso called

globoid cell leukodystrophy

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>

Section of brain with Krabbe disease

Globoid cells around blood vessels (blue arrows)

Pattern of Inheritance

Pedigree

Punnett Square

autosomal

recessive

R = normalr = Krabbe Disease

=female /male carrier

=affected with Krabbe disease

R r R

RR Rr

r

Rr rr

Location of the gene

Located on the GALC gene“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 gene30-kb delUsually 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 delThe G270D/ G809A allows for some myelin to be

made for some time, so onset of the disease is delayed1. GALC. National Institute of Health, 1 Mar. 2007. Web. 7 Mar. 2011. <http://ghr.nlm.nih.gov/gene/GALC>.

2. 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 rigidHearing lossFeeding difficultiesRandom feversUsually dies before age of 2

Late-onsetNot as severe, more likely to live longerSymptoms vary from person to person○ Walking difficulties○ Vision problems○ Rigid musclesKrabbe 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

clinicallyNarins, 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 KrabbeObserved the condition in two siblingsDescribed 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 rateOne 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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