1. Angela Qiu
Krabbe Disease

2. 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 Web. 7 Mar
<

3. 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, vols. Print.

4. 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, Print.
2. “Leukodystrophies.” UCSF. 6 Mar <

5. 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

6. 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 Web. 7 Mar
<
2. “GALC.” Digital. National Institute of Health. 6 Mar <

7. 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 Web. 7 Mar <
Wenger, David A. Krabbe Disease. 19 June Web. 4 Mar <

8. 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. <

9. 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 Web. 7 Mar < />.

10. 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, vols. Print.

11. 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, Print.

12. 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 Web. 4 Mar
<

13. Bibliography
“Beta-galactosidase.” Computer generated. UniProt. UCSC Genome Bioinformatics. Web. 7 Mar <
Dugdale, David C. Myelin. Ed. David Zieve. National Institute of Health, 21 May Web. 7 Mar <
GALC. National Institute of Health, 1 Mar Web. 7 Mar <
“GALC.” Digital. National Institute of Health. Web. 6 Mar <
Krabbe Disease. Ed. Chad Haldeman-Englert and David Zieve. National Institute of Health, 15 Apr Web. 7 Mar < />.

14. Bibliography (cont.)
Krabbe Disease. National Institute of Health, 27 Oct Web. 7 Mar <
“Leukodystrophies.” UCSF. Web. 6 Mar <
Narins, Brigham, ed. The Gale Encyclopedia of Genetic Disorders. 2nd ed. Vol. 1. Farmington Hills: Thomson Gale, vols. Print.
Wenger, David A. Krabbe Disease. National Institute of Health, 19 June Web. 4 Mar <
Wynbrandt, James, and Mark D. Ludman. Genetic Disorders and Birth Defects. 2nd ed. New York: Facts on File, Print.

15. :D