Newborn screening

It's also a story about how the economics of a rare disease drug development works.

A recent publication looked at the efficacy of newborn screening to detect and treat Metachromatic Leukodystrophy, or MLD, in Europe.

Jim, why is this study relevant?

It is relevant because it increases the evidence needed to make MLD part of newborn screening in the US, which is extremely important.

Before I get into the published study, a brief background on MLD.

It is a rare neurodegenerative disorder.

MLD does have a treatment available, but it is only indicated for patients who are diagnosed before the decline occurs, which creates a bit of a catch-22.

The babies look healthy, so there's no reason to test them for this very rare condition.

This could be recording this in the UK.

Of course, we are slightly different to the rest of Europe in that we don't have biochemical newborn screening.

So we're often not faced with that particular clinical scenario of an apparently well baby with a raised citrulline.

So in our experience, actually what distinguishes citrulline from those other conditions is usually how sick the baby is.

And can I ask, we're talking about the importance of treating from an early age.

That obviously brings about how early we should be diagnosing or whether we should even be screening for citrin deficiency.

So can current newborn screening practices reliably identify citrin deficiency?

My answer to that would be that newborn screening can currently not be recommended because there's no test that has an acceptable sensitivity and specificity.

Yeah, that's a nice and simple treatment, right? What could go wrong with that? I do want to explore that a little bit more, but just wanted to do a quick segue with what David had talked about before, which is diagnosing those patients by chance.

And I think that that's our perfect time to talk about newborn screening for these disorders, right? So we have already newborn screening for other disorders of sugar metabolism, like galactosemia.

And at the most recent SIMD meeting, I just wanted to bring that Dr. Miao He at CHOP presented some really cool data about using glycoforms, specifically what she calls mannose 4A versus mannose 4B, to distinguish hereditary fructose intolerance from glycosylation disorders and potentially detect that on newborn screening.

David and, uh, Martijn, do any of you want to elaborate a little bit more about newborn screening for HFI? Why would we do it, and how would we do it?

Do we wanna do it? [chuckles]

Well, actually, um, last week, I spoke with, um, patient organizations from UK and Australia, and, well, this was the topic that they are really involved in.

So they really would like to have a newborn screening on HFI.

I think if you would apply all the criteria for newborn screening, you could discuss whether they would apply to HFI.

This one seems to us was always a little bit more slowly progressive, which is why I, I felt it humbling to see the continued, uh, decline in the control arm even over that 15 months.

Tell us about the challenge of now getting this on the newborn screening panels and, and that process.

Newborn screening is a public health initiative, and what I mean by that is there is, there are many competing priorities for public health challenges, you know, not just rare disease.

So I, I will say that first and foremost.

The second thing to know is GFAP is rapidly accumulating in young patients, but we have not yet demonstrated whether it's high enough to be detectable at birth.

Right.

So in America today, if you have a baby, your baby does receive a newborn screening unless you know that you want to opt out and you live in one of the 47 states that will allow you to opt out because three of the states will put a misdemeanor on the mother.

Which ones are those? Nevada, California, and there's one other.

And I think it's a surprising one.

Oh, okay.

Something surprising.

So, and the whole thing about this newborn screening is, and I was listening to something even since we talked, and this gentleman who's one of the heads of the policy for newborn screening said, the litmus test for adding a condition to newborn screening, so the heel prick at birth, has always been if this rises to the severity that we would take a child from the mom for saying no, then we can add it to the screen.

So, friends, that's what's being added to the newborn screening are conditions where the medical cartel is going to tell you if baby has A, you must do B.

And this...

It's from the newborn screening through which many of these are detected.

Okay.

Yes.

So every year, we are adding 15,000 to about 18,000 babies.

Yes.

Interestingly, you've just mentioned newborn screening or testing.

How far are we with this? This is something I used to do with Prof.

Yeah.

Well, I'm really happy that you say that because, you know, we've got this nationally mandated newborn screening that happens within the first 24 to 48 hours of a child's birth.

OK.

And on that list is sickle cell.