Krabbe Disease – What is it?

Krabbe Disease  (Pronounced “Crab-bay”)

What Causes Krabbe Disease?

Krabbe Disease is anautosomal disorder resulting from a deficiency in an enzyme known as Galactocerebrosidase (GALC). Please refer to the ULF website fact sheet on genetics for more information about what this type of genetic inheritance  means.  GALC is an enzyme that breaks down molecules called galactolipids, which are heavily present in the brain.  There are many different types of galactolipids, but the buildup of one in particular, called psychosine, appears to be responsible for a good deal of the pathology of Krabbe disease.  In patients with Krabbe disease, psychosine can be at levels of over 100 times then that of healthy individuals, and this build up is thought to lead to the demyelination observed in Krabbe disease patients.

Another name for Krabbe disease is Globoid Cell leukodystrophy.  This name comes from a characteristic pathology of Krabbe disease, where a specific type of cell (called  the macrophage) accumulates high levels of undegraded galactolipids as a result of the lack of GALC activity.  These cells look different from healthy cells, and are termed “Globoid Cells”.

What are the “symtoms” of Krabbe Disease?

In the majority of cases pertaining to Krabbe disease, symtoms  appear usually within the first year of the patient’s life.  The patients rapidly regress to a condition with little to no brain function, and generally die by the age of 2 years, although in some cases, patients have lived longer than the norm.  With the addition of a feeding tube, and other life sustaining devices, the length of life can be extended a while longer, although the patients quality of life greatly diminish’s.  Death generally occurs as a result of a respiratory infection or brain fever.  Symptoms that may be encountered in the infantile form of Krabbe disease include:

  • Developmental delay
  • Seizures
  • Limb stiffness
  • Optic atrophy: wasting of a muscle of the eye, resulting in vision diffculties.
  • Neurosensoral deafness
  • Extreme irritability
  • Spasticity: presence of spasams
  • Ataxia: loss of the ability to control muscular movement
  • Progressive psychomotor decline: progressive decline in the cooridnation of movement

Although the majority of Krabbe disease patients show symtoms within the first year of life, there have been cases diagnosed at all ages, thru late adulthood. In general, the earlier diagnosis, the more rapid the progression of the disease.  Those who show symptoms at ages 2-14 will regress and become severely incapacitated, and generally will die 2-7 years following diagnosis. Some patients who have been diagnosed in the adolescent and adult years may have symptoms that remain confined to weakness without any intellectual deterioration, while others may become bedridden and deteriorate both mentally and physically.

How is Krabbe Disease Diagnosed?

Krabbe disease can be diagnosed by a biochemical assay that measures the GALC activity from a blood sample or skin biopsy. It should be noted that the absolute level of GALC activity is not an indicator of prognosis; that is, a particulary low GALC activity does not necessarily predict a more rapid progression of disease than a somewhat higher GALC activity.  The genitic basis for Krabbe disease is known, so it also may be possible to perform DNA sequencing of the gene in order to confirm the diagnosis of Krabbe disease.  In conjunction with genetic counseling, this knowledge may also allow relatives of patients with Krabbe disease to be tested for the presence of the genitic mutation responsible, allowing them to make informed decisions about having children.

How is Krabbe treated?

Most treatment of Krabbe disease is supportive.  However, one medical treatment that has been demonstrated to have some effect is the hematopoietic stem cell transplant (HSCT). This method appears to be of some benefit in cases of later onset or in infantile patients who have been diagnosed before or at birth.  The clinical course of patients who have received the transplant seems to be less severe, and an improvement in the pathology of the disease can be seen by MRI.  However, HSCT does not appear to be benificial in the case of infantile patients who have already begun displaying the symtoms of Krabbe disease. HSCT has been attempted on numerous fetuses with Krabbe disease, and failed in all cases, presumably because the donor cells were not sufficiently engrafted.

How is research on Krabbe Disease progressing towards better treatments?

Krabbe Disease in unique in that it has 3 animal models of disease that can be studied; a mouse model, dog model and a monkey model.  The mouse model is sometimes referred to as the “twitcher mouse”, and carries the same genetic defect found in patients with Krabbe Disease.  Various treatments have been attempted on these animal models, with varying degrees of success.  Some promising treatments are genetic therapy, where the deficient gene (GLAC) is delivered in a harmless virus.  Another promising method of treatment is stem cell therapy, which can provide healthy cells with GALC activity to allow for remyelination.  The other is Cord Blood Transplant, where umbilical cord blood from a healthy child is transfused into the blood of the affected person. Both methods are being  tested and in some cases used, and are showing some great promise!  However, these must be done before the patient develops the symtoms, which makes Newborn Screening for this disease so very iomportant.

Krabbe Disease is also know as:

  • Globoid cell Leukodystrophy
  • Globoid cell Leukoencephalopathy
  • Galactosylceramide beta-galactosidase deficiency
  • Galactocerebrosidase deficiency
  • GALC deficiency

 

(info supplied from the ULF website)

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