Pop T.: Wilson’s disease

Sir, for want of a better approach, let's start with the oldest of the articles that you've supplied.

You contributed to a large collaborative study, published in 2019, led in Wien by Ferenczi Peter, titled Age and Sex, but Not ATP7B Genotype, Effectively Influenced the Clinical Phenotype of Wilson Disease.

You had nearly 1,200 index patients.

1, 1, 7, 2, 185 siblings, all with a Leipzig score greater than 4, or 4 and greater than 4.

679 of them were male, 678 were female, and 79%, 4 out of 5, had documented biallelic ATP7B variants.

You classified these as having either hepatic or neurologic disease .

Interestingly, you found that hepatic presentation was more common in females 328 men or boys and 383 girls or women, and neurologic presentation in males, 259 versus 202, with substantial statistical significance, a p-value less than 0.001 for both.

Now, you didn't really find much of a correlation between variant per se and presentation, but you did find that being a woman tended to mean that you were going to be presenting with liver disease rather than with neurologic symptoms.

What is known about hormonal influences on ceruloplasmin metabolism?

First, I have to mention that this work, it was a huge work of Professor Ferenti and I was honored to be part of this study.

He was, I have to mention, he was the one who helped us with genetic tests for all our patients for the last 20 years.

25 years, all our patient children have the genetic background performed by the lab of Professor Ferenczi.

This paper was one of the greatest papers of the biggest cohort for studying the natural history of Wilson disease.

And because there are there are trends to see if there is a correlation between variants and the phenotype, the genotype and phenotype in Wilson disease.

But the conclusions were that only slightly correlation with the hormone, the sex, the female could be more with liver disease, not with neurological.

And the second important thing was related to the age.

So there is clear that the liver disease came before the neurological disease with mainly 10 years.

So it's not a very strong correlation, but these are the only things.

In the world, there are a lot of groups that are trying to correlate genotype, phenotype, the sex of the patient with the presentation, but the results are not clear.

Yes, that's pretty much what I took away from the article.

But in the seven years since that was published, has any work been done on estrogens or other sex-associated hormones and how they might alter ceruloplasmin metabolism?

Fortunately I was not aware about the following of this paper regarding the hormones and the seroloplasmin because in the presentation it's mainly from the clinical point of view there are mainly the acute presentation with hemolytic anemia could be linked with female sex So there is a presentation, very severe presentation that is almost four to one in a female compared to men.