Genetic testing offers hope for future treatment options for Pauline

Genomic testing is a powerful tool – not just for diagnostic purposes, but also for treatment options. Many patients with genetic conditions look to testing programmes to provide them with more information on appropriate courses of action in treating their conditions.

One such individual is Pauline O’Connor, author and member of Central and South Genomics Patient and Public Involvement Group. We caught up with Pauline to find out more about her condition and what genomic testing has been able to do for her.

Pauline was just a week old when she was diagnosed with phenylketonuria, also known as PKU.

“Newborn screening for PKU has been rolled out across the country since around the late 1960s. By the time I was born in the 80s, it wasn’t everywhere – but luckily, I was born into a family of healthcare professionals. Because I wasn’t the firstborn, within a week my family could see there was something off.

“They ran the test and I was diagnosed with PKU”.

PKU affects around 1 in every 10,000 people. Those with the condition are missing an enzyme called phenylalanine hydroxylase, which leads to problems breaking down the amino acid phenylalanine and causes harmful levels of it to build up in the blood. It’s an inherited disorder, with those diagnosed receiving two faulty copies of the gene for PKU, one from each parent.

Symptoms vary, and can range from brain fog, anxiety, headaches and shaking through to seizures and brain damage. Pauline stated, “If I were to eat a normal amount of protein, that one amino acid would build up in my blood, give me brain damage and affect my central nervous system.”

Due to the nature of the condition, treatment was, for a long time, restricted to diet therapy. Pauline noted, “For the first 30 years of my life, the only available therapy was restricted diet.

“I limit my protein intake and calculate absolutely everything. For example, there are around 6 grams of protein in an egg: that’s more protein than I can have in a day. I’d say around 85% of foods are off limits to me.”

The specific amount of protein intake one is allowed depends on the patient, and testing has been trial and error.

“It’s quite a frustrating and laborious approach – you start with not eating any protein and build it up, because if you get it wrong, you could cause damage. I call it the ‘goldilocks zone’ – you’re searching for the perfect amount. Some people aren’t able to consume any protein at all, whilst some patients can have even 30 grams.”

PKU was previously diagnosed through what is known as a ‘nappy test’, which involved pressing a paper strip containing ferric chloride onto a wet nappy. If the strip turned a dark blue, it was a positive result for PKU. However, in 1960, Dr Robert Guthrie developed the blood spot test, also known as the heel prick test, to diagnose PKU. The test uses a blood sample collected from a baby’s heel onto a special filter paper which is sent to a laboratory for testing. This can easily spot PKU by examining the levels of amino acids in the baby’s blood.

The blood spot test is still used today, with the test usually carried out within five days of birth, but in recent years genomic testing has come to the fore by expanding treatment options for patients with PKU.

In late 2021, NICE recommended sapropterin as a treatment option for certain people with PKU. As recalled by Pauline, “A new therapy came along which works for about 1/3 of people with PKU, but only those with responsive genomes. Once this was approved by NICE, a lot of us with the condition went through genomic testing to see if we’d be eligible.

“I was tested and unfortunately, I don’t have those genes. I did question it, because there are nearly 1000 genome types involved in this. I knew that one of my genes wouldn’t respond, but didn’t know about the other one. I was told statistically it wouldn’t, but I requested further testing, which was provided.

“I was effectively living on a trial for a year, and the outcome was that it wouldn’t work for me. It’s a shame, but it’s great to see that others with the condition are able to move away from just using diet therapy.”

Pauline still relies on restrictive diet therapy to manage her condition, noting the difficulties that food trends can pose for people with metabolic conditions.

“In my day-to-day life, control is a really important word. Because of the form of therapy we’ve had up until now, the burden of treatment falls on the patient and their family. It’s ongoing – you have to eat!

“If I have two extra biscuits with my tea, it changes what I get to have for my dinner. For those of us with PKU, the most terrifying phrase is ‘new and improved recipe’, because at the moment, it usually means that they’ve added more protein to the food. There are things I used to enjoy that I can’t have anymore due to the protein levels.

“In 2015 to 2020, when veganism was booming, it was easier, as there were lots of options like mushroom sausages – things that are low in protein. At the moment, everything is about protein.”

Pauline also pointed out the extra layer of consideration that those with PKU have to give to exercise.

“There’s an additional physical layer to do with exercise and muscle building. As we age, we’re told to exercise and eat more protein, but this isn’t possible for people with PKU. Protein affects bone density and muscle, but there’s not much information for older PKU patients.

“I also have to be careful about exercising and consuming calories afterward. Exercise breaks down fat and some protein, which then raises the level of protein in my bloodstream. It’s something that I must consider, because I could have consumed less protein than the maximum but still have too much in my blood due to a workout.”

Despite the restrictions PKU places on Pauline’s day-to-day life, she’s hopeful for the future.

“Genomic testing is becoming more commonplace and we’re seeing great advancements. It would be great if testing could start to play a part in determining which treatments are appropriate and which level of diet therapy is appropriate.

“I can see a real future where genomic testing could start to personalise current treatments as well as offering new ones”.