Neonatal Hemochromatosis


An Italian team of doctors has now published a paper (abstract here) where they appear to have successfully used exchange transfusions to treat Neonatal Hemochromatosis (“NH”) in a new born. This potentially offers hope to parents who, without any prior warning, find out at birth that their child has NH.

The great progress that Dr Whitington and his team are making with their pregnant mother IVIg treatment has an obvious downside: you have to know there is a possibility the child about to be born will have NH. Anecdotally the odds are around 1 in 100,000. So, given the cost and huge commitment (read about Mary’s experience here), you’re not going to have this treatment unless there’s a good chance the baby will have NH. As it happens there is a good(?!) test – if you’ve previously had a baby with NH there’s an 80% chance that your future children will also suffer the disease. In practice, the tradgedy is that you’ve probably lost a child before the benefits of the IVIg treatment in future pregnancies are available.

We’ve blogged previously about antioxidant and iron chelation therapy (here), and up until now this therapy, along with liver transplantation, were the only treatments available to new borns suffering from NH.  Exchange transfustions involve removing red blood cells or platelets and replacing them with transfused blood product.  It is used as a treatment for other alloimmune diseases in new borns.  It will be interesting to see whether this becomes a more standard and accepted treatment for new borns who present with NH symptoms at birth.

Dr Peter Whitington, who developed the IVIg gestational treatment that Mary underwent, has published another paper.

Neonatal Hemochromatosis: A Congenital Alloimmune Hepatitis, Seminars on Liver Disease, 2007, Vol 27, pp 243-250.

I haven’t had the opportunity to review the paper yet, however the abstract states recent research has confirmed Dr Whitington’s alloimmune hypothesis.  Proof of this came through lab tests on mice which were able to reproduce the disease.  The title of the paper suggests that the disease should be renamed “congenital” (medical condition present at birth) “alloimmune” (see the wikipedia definition here) “hepatitis” (causing liver damage). Makes sense.

This research will hopefully one day help identify the antigen responsible for the alloimmune problems and lead to a simple and cheap treatment for the mothers of NH babies in subsequent pregnancies.  I look forward to providing a more thorough lay person review (I’ll have the medical dictionary handy) once I’ve got a full copy of the paper.

There appears to have been quite a bit of coverage lately on a recent journal article by Grabhorn et al (actually it’s not so recent anymore – took a while for me to investigate it). The Birth and Breastfeeding News blog, an article distributed by Reuters Health, and an update on the neonatalhemochromatosis.org all report on the findings of the paper. The favourable outcomes the paper refers to are all about increased successful outcomes when infants are treated with an antioxidant-chelator therapy and/or receive liver transplantations. The antioxidant-chelator therapy is essentially a cocktail of drugs that help mop up the damaging excess iron and free radicals in the body of babies born with NH.

I’ve attempted to summarise the results from the study as clearly as possible below.

  • 4 infants received no treatment at all
    • 3 died within 25d, a good outcome for the other
  • 5 infants received antioxidant-chelator therapy only
    • 1 died at6 weeks, the other four had good outcomes
  • 5 infants received antioxidant-chelator therapy followed by liver transplantation
    • 1 died at 26 months, the other four had good outcomes
  • 2 infants received a liver transplantation
    • both infants had good outcomes

This all sounds really good, but you have to bear in mind a few things. In our experience the doctors were not alert to the possibility of NH as a diagnosis (you can’t really blame them, this is a rare disease). In fact Ellen’s diagnosis was only confirmed after an autopsy, so the chances of getting this treatment if no-one is expecting it are low. But for Harry we were alert to the high chance of recurrence. As you can see above the odds are still not great, but they do seem to improve with the antioxidant-chelator therapy.

Liver transplantation has long been known to be a successful way of treating babies with NH, but our advice from doctors was that you would have to be pretty lucky to get one in time.

When we became pregnant with Harry, news of the antioxidant-chelator therapy was the first bit of hope that we might have a healthy baby. I think one of the Doctors gave us a copy of a paper by Flynn et al.

However, like so many things associated with NH, it’s not all black and white. Leonis & Balistreri point out that there are agents within the antioxidant-chelator cocktail that may be potentially dangerous to newborns. They also refer to a paper by Rodrigues et al who studied 19 infants and found outcomes of the 10 infants who received antioxidant-chelator therapy were nearly identicle to the 9 that did not.

But then again… Flynn concluded that:

…Early treatment with antioxidant cocktail is beneficial and may be curative in those who present with milder phenotype [Note: this seems to have been what happened with Harry]. Liver transplantation should always be considered at an early stage in non-responders and in children with more severe acute liver failure.

So what does it all mean? I don’t really know (which is not surprising considering my completely non-extensive medical experience!). Like everything else it just means you need to ask lots of questions… and that there’s always something more behind the quick media releases (but you knew that already).

Finally, the treatment does not appear to have anywhere near the success associated with the IVIg treatment (that Mary had with Harry) which results in babies who present with a much milder form of NH. For the record, Harry received Vitamin E (an antioxidant), but not the complete chelator cocktail, after he was born as part of the standard treatment when his ferritin levels were found to be high.

I understand Dr Whitington will be publishing a new paper updating the progress of the IVIg treatment in the coming months, so I’ll report back then.

References

  1. Grabhorn, E., Richter, A., Burdelski, M., Rogiers, X., and Ganschow, R., 2006, “Neonatal Hemochromatosis: Long-term Experience With Favorable Outcome” PEDIATRICS, Vol. 118 No. 5 November 2006, pp. 2060-2065 (doi:10.1542/peds.2006-0908)
  2. Leonis, M & Balistreri, W, 2005, “Neonatal hemochromatosis: It’s OK to say ‘NO’ to antioxidant-chelator therapy”, Liver Transplantation, Vol 11, Issue 11, pp1323-1325 (doi:10.1002/lt.20541)
  3. Rodrigues F, Kallas M, Nash R, Cheeseman P, D’Antiga L, Rela M, Heaton N, Mieli-Vergani G, 2005, “Neonatal hemochromatosis-medical treatment vs. transplantation: the Kings experience” Liver Transplantation, Vol 11: pp1417-1424
  4. Flynn D, Mohan N, McKiernan P, Beath S, Buckels J, Mayer D, Kelly D, 2002, “Progress in treatment and outcome for children with neonatal haemochromatosis”, Archives of Disease in Childhood Fetal and Neonatal Edition, 88:F124

Here’s some more good news on the treatment of neonatal hemochromatosis (NH).

Over at the Macclesfield Hospital in Cheshire, England, little William celebrated his first birthday back in February this year. William’s parents lost their daughter, Elizabeth, to NH even though she received an emergency liver transplant. Like Mary, William’s mum underwent the IVIg treatment through her doctors at the hospital and with the help of Dr Whitington. William’s now doing fine thanks to the determination of his parents and the success of the treatment. Click here to read the complete article from the Wilmslow Express.

A similarly successful outcome was also published online in the Journal Prenatal Diagnosis last month. Venkat-Raman et al (see link below) report on the successful maternal intravenous immunoglobulin treatment of a woman with a previous history of NH. In this case the woman had two successive previous pregnancies where the babies had died from NH, which causes severe liver damage and excessive iron deposition in other cells in the body. Like Mary’s experience, the woman started the IVIg treatment for her latest pregnancy at week 18 and continued until an elective caesarean section at 38 weeks. The baby boy was born with elevated ferritin levels (the protein associated with iron storage) and some signs of decreased liver and coagulation function. However, all these indicators returned to normal within a couple of months and the child made an “excellent recovery”. It’s interesting that the mother received the same ‘brand’ (Sandoglobulin) of immunoglobulin as Mary and the dosage rates (6% solution at a maximum rate of 150mL/h) were also the same, hence the poor mum would have been receiving the infusion for at least 9h!. We have heard from mums where the rates of infusion are much higher hence the time taken for infusions can be as short as 3-4h.

Venkat-Raman et al concluded that the recurrence risk of NH is high but that the immunoglobulin treatment “appears to alter the course of the disease with better infant survival”.

References

Andrew and Stacey contacted us a while back after they tragically lost their son Teyte to NH.  They have now set up a website (teytesmum.com) that tells their story.  Hopefully Dr Whitington’s treatment may help them have a healthy child in the future.

It’s been an amazing few months.  As I’ve been telling people, when I went to work during the first 8 months of Harry’s life I didn’t feel like I was missing out on too much (he didn’t really change too quickly).  But now he seems to be doing something different almost every single day.  This evening he gave us a piano performance (apologies for the injudicious video editing).

The last few weeks have also reminded us what we went through to bring Harry into the world.  A couple of other web sites are referring to our site (NHIC, blogher) and we’ve also been emailing couples who’ve been through similar experiences in Canada, New Zealand and Perth.  The tragedy is that to get to this point we’ve all lost a child.

<i>Townsville Bulletin</i>, May 16, 2006

In case you didn’t catch the Townsville Bulletin last week, Harry’s story made the front page. This was backed up with a great article on Page 5 (Click Here for the link to the article). There was even an editorial!

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