KRABBE’S DISEASEBY ALI LORD AND GARD HERLOFSEN

WHAT IS KRABBE’S DISEASE?Krabbe’s disease (globoid cell

leukodystrophy) is a degenerative disorder that affects the nervous system.

It’s hereditary autosomal recessive disease.

Occurrence of 1 in 100,000 newborns.

It affects the myelin sheath of the nervous system.

Knud Haraldsen Krabbe.

HOW IS KRABBE DISEASE CAUSED?Mutations in the GALC gene,

causing deficiency of enzyme galactosylceramidase.

This effects the growth and maintenance of myelin, which causes severe degeneration of motor skills.

Krabbe disease is a leukodystrophy.

Fig.1 – www1.

DIAGNOSIS AND SYMPTOMSDifferential diagnosis by presence of

multinucleated globoid cells.

Histological staining by Luxol blue for myelin.

Symptoms it causes are neurological.

Fever, Muscle weakness and Stiffness.

Type 1 - the infantile form is the most common,

Three stages -: Stage 1: 3 – 6 months, stops developing,

becomes irritable and has high muscle tone, trouble feeding.

Stage 2: Rapid nerve cell damage, leading to loss of use of muscles, damage to vision, seizures.

Stage 3: Blindness, deafness, fixed in a stiff posture. Lifespan in Type 1 is 13 months.

Type 2, 3, and 4. Do not survive beyond two years, but in Types 3 and 4 may vary.

Fig.4 – www2

MRI Scans revealing formation of myelin

PATHOLOGYCentral Nervous System

Rare autosomal recessive disease deficiency of GALC enzyme.

GALC liposomal hydrolysis of galactolipids formed during myelination

Pathological changes in CNS/PNS toxic, accumulated psychosine

Cannot be degraded deficiency of GALCMajor changes: demyelination of fibers,

reduction of oligondendroglia cells

TREATMENTNo cure.

Physical Therapy.

Bone marrow transplant.

Cord Blood Transplant.

PROGNOSISHigh fatality rate in infants – generally

occuring before the age of 2.

Late-onset of disease in patients live significantly longer due to slower progression.

Despite no cure, treatments specifically a marrow or blood cord transplants, have been effective in the early course of the disease.

CONCLUSIONAffects infants between the ages of 0-2 years

and has a very high risk of fatality .

Higher prevalence in Scandinavian countries (1 in 50,000).

It is caused by the shortage of enzyme galactosylceramidase , effecting the myelin sheath of the nervous system.

No cure but methods are being developed.

ReferencesRosenberg.R, Dimauro.S, Paulson.H, Ptacek.L and

Nestler.E (2008). The molecular and genetic basis of neurological and psychiatric disease. 4th ed. Philadelphia: Lipincotts Williams and Wilkins. 240-242.

Goldman.S, Schanz.S and Windrem.M.. (2008). Division of Cell and Gene Therapy and Center for Translational Neuromedicine. Stem cell-based strategies for treating pediatric disorders of myelin.. 17 (1), 76-83.

www1 – http://www.youngcarers.net.au/Uploads/stories/ms_nerve_cell.jpg.

www2 –

http://research.unc.edu/endeavors/fall2005/images/brain_scans.gif.

• www3- http://ghr.nlm.nih.gov/gene=galc.• www4-http://www.marrow.org/PATIENT/

Undrstnd_Disease_Treat/Lrn_about_Disease/Metabolic_Storage/GLD_and_Tx/index.html.