Krabbe Disease

Case study of Krabbe Disease.

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 B lood 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