Maternal PKU and Glycomacropeptide (GMP)

Maternal PKU and Glycomacropeptide (GMP)

Charlotte Ellerton, Specialist Metabolic Dietitian, BSc (Hons) PgDip, National Hospital for Neurology & Neurosurgery, London, UK
For any adult metabolic dietitian, supporting women during pregnancy is one of our key roles.
"The fantastic achievements we see are due to the motivation, determination and sheer hard work of each and every woman to protect their unborn children"
I have worked as a dietitian in Inborn Errors of Metabolism (IEM) for many years and have a special interest in pregnancy in IEM. To me, it is one of the most magical areas of dietetics. With the right support, every woman with PKU has the possibility to have a healthy baby, unaffected by maternal PKU syndrome1.

Outcomes across the world for treated pregnancies in PKU are overwhelmingly positive. However, that is not to suggest in any way that it is easy. The fantastic achievements we see are due to the motivation, determination and sheer hard work of each and every woman to protect their unborn children.
Diet and pregnancy
Women with PKU who are pregnant or planning a pregnancy have to follow an incredibly strict diet – often just a few grams of protein per day. They can only achieve the targets set for them by using lots of the specialist low protein foods, and taking their protein substitutes three or perhaps four times daily. They send in blood tests several times per week, waiting anxiously for results.

It is an understatement to say that the diet is tough. Bracing yourself to take another protein substitute, when just an hour before, you had to rush to the bathroom when trying to take the first. Ignoring your cravings for mashed potato because you don’t have enough exchanges left for the day. Not opening a family sized bar of chocolate because your period came again and you know you’re not pregnant, despite it being what you desperately want. It takes such strength.
Glycomacropeptide
However, despite the diet being such a huge burden, at present we have no other option. Future treatments may make the diet obsolete for pregnancy – but that doesn’t help women right now. That is why the continual development of products to make the diet even just a tiny bit easier is so important.

Glycomacropeptide (GMP) is a naturally occurring peptide produced as a by-product of cheese manufacturing. Its low phenylalanine content means it can be used in PKU protein substitutes (with careful alterations) as an alternative to purely amino acid based products2-4.

The literature suggests that GMP might hold huge potential for use in PKU in terms of gastrointestinal tolerance, bone health and satiety. However, in my opinion, currently the only conclusive evidence is that GMP products may offer benefits in terms of palatability5. In our clinic, we have seen a considerable rise in the number of patients choosing to use GMP-based protein substitutes as part of their PKU diet as they prefer them to amino acids.

Woman preparing meal | Maternal PKU and GMP Blog
GMP and pregnancy
"Can we use GMP-based protein substitutes in pregnancy? And if we can – how should we?"
Given its popularity, we should expect that women with PKU might wish to start (or continue) taking GMP-based substitutes when they are pregnant. Can we use GMP-based protein substitutes in pregnancy? And if we can – how should we?
As dietitians we are all about evidence-based practice, but that is where we hit something of a stumbling block. Studies of GMP to date have been carried out in children or non-pregnant adults5, and there are suggestions that because of this GMP should not yet be used in pregnancy6.

A small number of case studies have suggested good outcomes with partial GMP use7, and I would encourage anyone using GMP in pregnancy to write up their cases to help improve our knowledge.
My experience
In my own recent practice, I have used GMP during pregnancy – although cautiously, and on a personalised basis. There are no guidelines to suggest how we should use GMP in pregnancy, although my own experience means that I would certainly consider accounting for the additional phenylalanine, and possibly introducing slowly in some situations.

Anecdotally, in these cases it appeared to help with the reflux and nausea we see occurring in pregnancy – but we need studies to evaluate that in more detail, as well as looking at other effects of GMP on metabolic control, nutrition and pregnancy outcome.

What I do think is important is that women with PKU are not overlooked because of pregnancy. They should not be excluded from research or denied products that benefit others without good reason. We demand so much of these women for pregnancy – and they should be able to expect a lot from us in return.

References:

1. Dent C (1957) Discussion of Armstrong MD: Relation of biochemical abnormality to development of mental defect in phenylketonuria. In: Etiologic Factors in Mental Retardation: Report of Twenty-Third Ross Pediatric Research Conference November 8–9, 1956. Columbus, OH: Ross Laboratories; 32–332.

2. Lim K, van Calcar SC, Nelson KL, Gleason ST, Ney DM (2007) Acceptable low-phenylalanine foods and beverages can be made with glycomacropeptide from cheese whey for individuals with PKU. Molecular Genetics and Metabolism 92(1-2):176-8.

3. Ney DM, Gleason ST, Van Calcar SC, MacLeod EL, Nelson KL, Etzel MR, Rice GM, Wolff JA (2009) Nutritional management of PKU with glycomacropeptide from cheese whey. Journal of Inherited Metabolic Disease 32 (1): 32-9.

4. Van Calcar SC, Ney DM (2012) Food products made with glycomacropeptide, a low-phenylalanine whey protein, provide a new alternative to amino acid–based medical foods for nutrition management of phenylketonuria. Journal of the Academy of Nutrition and Dietetics. 112(8):1201-10.

5. Pena M, Pinto A, Daly A, MacDonald A, Azevedo L, Rocha J, Borges N (2018) The Use of Glycomacropeptide in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis. Nutrients 10 (11):1794.

6. Van Wegberg AMJ, MacDonald A, Ahring K, et al. (2017) The complete European guidelines on phenylketonuria: diagnosis and treatment Orphanet Journal of Rare Diseases 12:162.

7. Pinto A, Almeida MF, Cunha A, et al. (2017) Dietary management of maternal phenylketonuria with glycomacropeptide and amino acids supplements: A case report. Mol Gen Metab Reports. 13:105-10.