Krabbe disease: enzyme deficiency, genetic inheritance, and metabolic dysfunction

Krabbe disease (also known as globoid cell leukodystrophy) is defined as a degenerative disorder that affects the nervous system. According to the U.S. National Library of Medicine (2011) Krabbe disease is brought about by galactosylceramidase deficiency, which is an enzyme which assists in myelin maintenance which is a protection around some nerve cells responsible for transmission of nerve impulses.

The medics have suggested that this deficiency is inherited and leads to the loss of myelin which covers the nerve cells and expedites cell communication.

Krabbe Disease is also referred to using the below terms; Diffuse Globoid Body Sclerosis, Galactosylceramidase Deficiency Disease, Galactosylceramide lipidosis, galactosylcerebrosidase deficiency, galactosylsphingosine lipidosis, GALC deficiency, GCL, GLD and psychosine lipidosis as the recognized references in the medical practice.

Genetic component of the disease

The Krabbe disease patients are seen to have two copies of the GALC gene both of which are not functional. It is also noted that the biological parents of the patient with Krabbe disease have one normal and functioning GALC gene and the other GALC gene in nonfunctional making the parents healthy carriers.

Incase both parents are carriers then there is a 25% chance of the child to suffer Krabbe Disease. Also the child may have a 50% chance of being a healthy carrier and the chances that he will have two normal GALC genes is 25%. It is also noted that the siblings of the patient of this disease have 66% chance of also suffering from the same as discussed by Health Line, (2011).

The GALC gene is situated on the chromosome 14. It is interesting to note that the rate of exposure to the disease also varies according to ethnicity and race. For instance, Health Line suggests that there is a 45% chance of incurring a disease causing mutation due to deletion of one GALC gene among people of European ancestry and on the other hand those from the Mexican ancestry stand a 35% chance of the same exposure. University of Maryland Medical Center (2009), also suggests that people from Scandinavia are most likely to have the disease.

5. How and when do patients present to the doctor?

This disease usually shows up very early in the infancy barely a few months old and in cases of late-onset it can be at adolescence (New York Times, 2011). Most parents or guardians will present the patients display symptoms of seizure, abnormal posturing and falling unconscious. These are dangerous signs and the patient should hence be taken to the hospital fast.

6. What makes the doctor think of this disease as the cause of the patient's troubles?

There are reasonable signs that a doctor may use to suspect that the patient has krabbe disease and recommend further diagnosis on a patient. Hussain SA et.al (2011) says that the patient may display excessive irritability, developmental delay, muscle hypertonicity, peripheral neuropathy, optic nerve atrophy, failure to thrive and seizures. The doctors can, in rare conditions, detect proximal prechiasmatic enlargement of the nerves.

7. How is the disease diagnosed?

Once the patient is brought to the hospital, the doctors will conduct several test and diagnosis on the patient. These will involve conducting physical examination to verify the availability of the symptoms of the disease.

The doctor will also take blood samples and a skin sample for laboratory analysis, where the activities of the GALC enzyme will be measured. If the activity is found to be low, then the patient might be having Krabbe disease. These tests will however not show the rapidity of the activity of the disease but just confirms the presence of the disease as indicated by Mayo Clinic (2011). For a confirmation of the disease, there can be further diagnostic process as suggested by Cable News Network (2009) below:

Magnetic Resonance Imaging (MRI): this is the use of magnetic signals to create the images of the brain. This way, any abnormal development of the brain, a thing that is characteristic of Krabbe disease patients. A CT scan which is computer enhanced is also used in detecting this abnormal growth.

Nervous conduction studies: is measuring the velocity of impulses sent through the nervous system. This can be through stimulation of nerves and taking the time it takes to reach the recording device. In the presence of Krabbe disease, then the transmission will be slower.

Eye examination: an ophthalmologist (specialist in the eye) can look for any signs of visual deterioration on the retina

Genetic testing: this can involve the look into the genetic mutations that are associated with the disease.

Doctors can also draw the amniotic fluid from the pregnant women and screen the cells in the fluid for any activities of the GALC enzymes.

8. Treatment of Krabbe disease

The Krabbe disease has for long not had any mitigation in the medical circles, indeed even to date there are some medics who are still skeptical about the medication that are in existence. However, there was a study on some 5 children treated with hematopoietic stem cell transplantation. There was a noticeable reversal or retardation of the disease exhibited among them, it was however noted that early detection and constant monitoring was essential as indicated by Alexander C. Guo, (2001).

The other treatment that has been proven to reduce the effects of the disease is the implanting umbilical cord blood stem cells from unrelated donors prior to symptom onset. This is noted by the National Institute of Neurological Disorders and Stroke (2010) to reduce heavily the manifestations of the symptoms in the later life after birth.

9. Challenges and help for Krabbe disease patients

The patients of this disease can face social discrimination if the late onset is the case, this will be at the adolescent and when they start displaying the mental deterioration, then the peers might start ruining away from them hence subjecting them to further trauma. Though there are state laws and federal laws that militate against discrimination at any levels, the application of this law is a challenge and the patients end up being discriminated against anyway. The victims will most likely end up in nursing homes where they will receive treatment but this separates them from the family life.

The other factor is the cost that weighs down the concerned people in terms of medical bills. It is a disease that is expensive to manage since there are numerous scans that one must get and the cost of specialized care doesn't make it any better. The good news however is that there are several organizations that have volunteered to help the victims of this disease like Hunters Hope (2009) which was purposefully formed to cater for patients of the disease in terms of support and information among many other organizations.

Reference

Alexander C. Guo, (2001). Evaluation of White Matter Anisotropy in Krabbe Disease with Diffusion Tensor MR Imaging: Initial Experience1. Retrieved April, 11, 2011 from http://radiology.rsna.org/content/218/3/809.full.pdf

Amie Stanley (2002). Krabbe Disease: Description. Retrieved April, 11, 2011 from http://www.healthline.com/galecontent/krabbe-disease

Cable News Network (2009). Krebba Disease: Tests and diagnosis. Retrieved April, 11, 2011

from http://edition.cnn.com/HEALTH/library/krabbe-disease/DS00937.html

Health Line, (2011). Krabbe disease. Retrieved April, 11, 2011 from http://www.healthline.com/galecontent/krabbe-disease

Hunters Hope (2009). About Hunters Hope: Mission. Retrieved April, 11, 2011 from http://www.huntershope.org/site/PageServer?pagename=aboutus_mission

Hussain SA et.al, (2011). Optic Nerve Enlargement in Krabbe Disease: A Pathophysiologic and Clinical Perspective. Retrieved April, 11, 2011 from http://www.ncbi.nlm.nih.gov/pubmed/21285037

Mayo Clinic (2011). Krabbe Disease: Tests and Diagnosis. Retrieved April, 11, 2011 from http://www.mayoclinic.com/health/krabbe-disease/DS00937/DSECTION=tests-and-diagnosis

National Institute of Neurological Disorders and Stroke (2010). NINDS Krabbe Disease

Retrieved April, 11, 2011 from Information Page. http://www.ninds.nih.gov/disorders/krabbe/krabbe.htm

New York Times, (2011). Health Guide: Krabbe Disease. Retrieved April, 11, 2011 from http://health.nytimes.com/health/guides/disease/krabbe-disease/overview.html

U.S National Library of Medicine (2011). Krabbe Disease. Retrieved April, 11, 2011 from http://ghr.nlm.nih.gov/condition/krabbe-disease

University of Maryland Medical Center (2009). Krabbe disease - Overview . Retrieved April, 11,

2011 from http://www.umm.edu/ency/article/001198.htm