Millie, a 3 month old girl, was brought to the pediatrician with issues feeding, irritability, and muscle spasms. Tests found she had no GALC enzyme activity and an MRI showed demyelination. She was diagnosed with Krabbe disease, a rare inherited disorder caused by mutations in the GALC gene resulting in myelin loss and impaired nervous system development. There is currently no approved treatment, but research is exploring inhibitors of enzymes involved in the disease process.

1. Krabbe Disease
By: Rachel Jonson

2. Consider the Following Patient
 Worried parents brought their 3 month old
daughter Millie to the pediatrician. They
said she had been having trouble feeding
and has been extremely irritable. They also
said she had recently been experiencing
muscle spasms. The pediatrician found that
Millie had a fever but was not showing signs
of an infection.

3. What tests would you use in
order to make a diagnosis?

4. Testing
Blood and skin samples were taken to
assess the level of GALC enzyme
activity.
In addition to the laboratory tests, an
MRI scan was performed to detect loss
of myelin.

5. Test Results
The blood and skin sample testing
detected no GALC enzyme activity
The MRI showed evidence of
demyelination

6. Diagnosis
 Millie was diagnosed with Krabbe disease.
 Krabbe disease is degenerative disorder that
effects the nervous system. It results in the
loss of myelin on neurons, leading to slowed
mental and physical development, muscle
weakness, and possibly death. It is an
uncommon disorder, only 1 case per 100,000
in the United States.

7. Genetics
 Krabbe disease is an inherited degenerative
disorder.
 It is caused by a mutation in the GALC gene. Over
70 GALC gene mutations have been determined to
cause Krabbe disease.
 It is inherited in an autosomal recessive pattern.
This means that two mutated genes must be
inherited, one from each parent. These disorders
are usually passed on by two carriers.

8. Galactosylceramidase (GALC)
 GALC is a lysosomal enzyme involved in the catabolism
of psychosine (galactosylsphingosine).Patients with
Krabbe disease typically have no GALC activity. Without
GALC activity, psychosine activates secretory
phospholipase A2 (sPLA2). The enzyme sPLA2 breaks
down lysophosphtidycholine (LPC) and arachidonic acid
(AA). The enzyme sPLA2 results in the death of
oligodendrocytes, which are responsible for myelin
formation.

9. Treatment
 There are currently no approved treatments for Krabbe
disease.
 Recently, scientist found that 7,7, dimethyl
eicosadienoic acid, an inhibitor of sPLA2, blocked
oligodendrcoyte cell death.
 Anticonvulsants can be given to reduce muscle spasms,
such as clonazepam.

10. References
 Mayo Clinic. (2014). Krabbe disease. Retreived from:
http://www.mayoclinic.org/diseases-conditions/krabbe-
disease/basics/treatment/con-20029450
 U.S. National Library of Medicine. (2012). Krabbe disease.
Retrieved from: https://ghr.nlm.nih.gov/condition/krabbe-
disease#genes
 Giri, S., Khan, M., Rattan, R., Singh, I., & Singh, A. (2006).
Krabbe disease: psychosine-mediated activation of
phospholipase A2 in oligodendrocyte cell death. The Journal
of Lipid Research, 47, 1478-1492. Retrieved from:
http://www.jlr.org/content/47/7/1478.full