In 2007 I diagnosed a 74 year old woman with CF.

She had a positive sweat test and positive mutation with an intronic mutation as well.

I investigated this after she had bronchiectasis and no history of smoking. And a grandson with CF......... Why did I do the sweat test?
I needed to know if her bronchiectasis was due to CFTR mutations. Maybe she didn't need COPD treatment after all.

That same intellectual curiosity is found in a recent study in the NEJM. It turns out they are finding some patients who have Gaucher's also have Parkinson's Disease.

What's even more interesting is that Heterzygotes for Gaucher's are at increased risk of sporadic or familial Parkinson's disease. So one has to wonder, how many Parkinon's cases are due to GBA mutations.....

Well, this study aimed to elucidate that. First off, if the GBA mutations are higher than LRRK2, well, we my have another Ashkenazi Jewish disease.

What did these guys do?

5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel–Haenszel procedure used to estimate odds ratios across centers. Ok, a reasonable method.

Now what did they find?

This finding allows for confidence in reporting the Mantel–Haenszel combined odds ratios for N370S (odds ratio, 3.96; 95% confidence interval [CI], 2.60 to 6.02) and L444P (odds ratio, 6.73; 95% CI, 4.50 to 15.42). After correcting for outliers they can confidently report a Mantel–Haenszel odds ratio of 5.43 for GBA mutations, in patients versus controls Ok, so if you have either of these mutations, you are at a pretty high risk for Parkinson's Disease. Seriously. How many of the Parkinson's cases are due to this type of carrier mutation? Overall, when screening solely for N370S and L444P, one of these two mutations was found in 15% of Ashkenazi Jewish patients as compared with 3% of Ashkenazi Jewish controls and in 3% of non–Ashkenazi Jewish patients as compared with less than 1% of non–Ashkenazi Jewish controls That's a lot of cases.

Way more than the LRRK2 mutation Familial Autosomal Dominant disease that could be counseled by pedigree alone that Serge was so hepped up about.

But if you want a breakdown of LRRK2 versus GBA you can read about it here.

Of note, there are very few papers comparing both, but there is one that disproved my hypothesis that it is likely that the LRRK2's actually are GBA mutation carriers.... But 37 Families still gives me a little hope that Serge was focused on the WRONG gene...

Back to GBA mutation carriers, this like CF now has me asking "Does anyone in your family have a genetic disease like Gaucher's" when I see some PD history.

Which highlights a significant point, if Primary Care Doctors are supposed to perform family histories, then how in the hell are they supposed to know about this?

The answer: This NEJM article? Navigenics? Who? How?

Unfortunately, most Internists will look at the article and say "Meh, another one of those genetics articles I don't understand" Will giving each doctor a FREE Navigenics test break that attitude......doubtful.

The Sherpa Says: Geneticists need to do their job and teach other doctors, not serve on DTC genomics boards.