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Here is a recent abstract (below) about an inherited disease caused by an enzyme deficiency, called Krabbe disease. Krabbe disease is a devastating disease that is usually shows up in infancy. It is autosomal recessive, meaning both parents have to carry the mutation. It is a demyelinating disease. It is a case report about a baby with Krabbe that cropped up in a family with several MS cases. The authors suggest that possible "MS coinheritances" made the disease more severe in this baby. I thought about it another way - that maybe the Krabbe case may be a clue for MS susceptibility- that carriers of the gene in this family might have subnormal levels of the enzyme and might be more likely to develop MS. I fervently hope that the researchers examine the baby's family to see if cases of MS also carry the gene for Krabbe disease. If so, that could be a potential major breakthrough for MS, particularly if carrier status is found in other individuals with MS outside this particular family.

If someone could access this article and see if the authors discuss that possibility or already looked into it, I would be very grateful.

Krabbe disease has gotten recent press in the U.S. because Hunter, a young son of a professional football player recently died of this disease. His parents formed a foundation and info on Krabbe dissease can be found on the website huntershope.org, for those interested.

The huntershope.org website indicates that in the U.S., about one out of every 125 people carry one copy of this gene, so even if Krabbe disease (resulting from two copies of the gene) is very rare, having one copy is actually not that uncommon, at least in the U.S. population.
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J Child Neurol. 2005 Oct;20(10):826-8. Links


Krabbe disease: severe neonatal presentation with a family history of multiple sclerosis.

Sahai I, Baris H, Kimonis V, Levy HL.

Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive disorder caused by a deficiency of a lysosomal enzyme, galactocerebrosidase. This defect prevents normal turnover of the galactolipids and results in progressive demyelination. In the infantile form, symptoms typically present at 3 to 6 months of age with subsequent neurologic deterioration. We report a case with presentation on day 7 of life and rapid progression culminating in death at 10 weeks. Galactocerebrosidase activity was absent in the leukocytes, and a 30 kb deletion in the GALC gene was found. To our knowledge, this is the earliest reported death from Krabbe disease. Several family members have multiple sclerosis, which is also a demyelinating disorder. We propose that the neonatal expression could be an example of complementary gene interaction in which coinheritance of a predisposition to multiple sclerosis led to the unusual early manifestation and rapid course of Krabbe disease in this infant. (J Child Neurol 2005;20:826-828).

PMID: 16417879 [PubMed - in process]
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Unfortunately this is a tough disease biochemically for which there is no easy dietary fix, unlike some other enzyme deficiency diseases. So if it turned out to be related somehow to MS susceptibility, I'm not sure what treatment would be available. Also, if it were related, it would take other factors besides being a Krabbe carrier to cause MS, because MS is more rare in the population than Krabbe carrier status.

On a positive note, at least for babies with Krabbe disease, there now appears some hope for treatment via cord blood transplants!

Lisa

Well, I heard back from the study authors and they indicated they also thought of the possibility that Krabbe disease carriers were at increased risk for MS. They discussed that thought in the body of the paper, which unfortunately I couldn't get - I only saw the abstract. Apparently they tested one of the family members with MS and the individual was found not to be a carrier. They haven't tested all the other family members with MS, though.

So the jury's still sort of out, but the limited data (of one person) suggests that the mutation that causes Krabbe disease is not a susceptibility gene for MS.

On the bright side (if there is one) if the Krabbe gene was somehow related to susceptibility to MS, at the current level of knowledge there is no easy fix.

I'll keep up the gene hunt and hope 1) to find something and 2) it's something fixable.

Lisa

LisaBee wrote:I'll keep up the gene hunt and hope 1) to find something and 2) it's something fixable.

Hi Lisa,
You may be interested in reading one of my posts from last February on a link between an interferon-gamma polymorphism and an increased risk for developing MS.

• Interferon gamma gene polymorphism linked to MS

There are also some links to the misregulation of the BCL gene family leading to a faulty apoptotic pathway and an increased risk for MS.

• Programmed cell death of myelin basic protein-specific T lymphocytes is reduced in patients with acute multiple sclerosis.
  J Neuroimmunol. 2005 Sep;166(1-2):173-9.
  
  Expression ratios of the Bcl-2 family proteins and disease activity in multiple sclerosis.
  J Neuroimmunol. 2003 Jan;134(1-2):158-65.

A PubMed search should reveal many others as well.

NHE

Hi NHE--

While I'm certain Lisa will find the info you posted fascinating, from the hormone corner I'm equally fascinated.

Here's an abstract Progesterone Differentially Regulates Pro- and Anti-Apoptotic Gene Expression in Cerebral Cortex Following TBI in Rats

progesterone significantly increased mRNA levels of the anti-apoptotic gene, bcl-2, but down-regulated pro-apoptotic gene expression (bax and bad) in cerebral cortex....

one of the neuroprotective mechanisms of progesterone may be related to its differential regulation of apoptotic signals.

Here's another finding on the topic.
Bcl-2-expressing oligodendrocytes in MS lesions

The expression of apoptosis-associated proteins may contribute to oligodendrocyte preservation or loss in MS lesions.

Thanks for the reminder of your posts on this last year. It seems to me that progesterone could theoretically have some role in all of this. What do you think?

Sharon