Metabolic Matters (Issue 7)

JULY 2022

YOUR MONTHLY MSUK MAGAZINE

Metabolic Matters

DOES DATA SAVE LIVES?

CONTENTS

Focus on: The "Data Saves Lives" strategy (Pages 4-5) Wessex Paediatric Study Day – Metabolic Medicine (Page 6) Please mind the gap...using real world evidence to increase access to innovation (Page 7) Know your IMD: CSID (Pages 8-9) Stronger together: Laboratory of Inborn Errors of Metabolism (Rio de Janeiro) (Pages 10-11) Keiron's story: Citrullinaemia(Pages 12-13) The London Marathon: Support our runners (Page 14) Get involved (Page 15)

Focus on: The "Data Saves Lives" strategy

What is the "Data Saves Lives" Strategy?

A UK government strategy showing how stakeholders can use data to bring benefits to all parts of health and social care – from patients and care users to staff on the frontline and pioneers driving the most cutting-edge research.

This plan further aims to bolster the £200M already invested in data for research and developments programmes. Enabling for the effective utilisation of health data to improve the UK’s healthcare system as a whole.

What are the key commitments?

Investing in secure data environments to power life-saving research and treatments Using technology to allow staff to spend more quality time with patients Giving people better access to their own data through shared care records and the NHS App How does this focus aim to improve healthcare?

Health and care: This plan aims to improve people’s trust in the health and care system’s use of data through giving healthcare professionals the information they need to provide the best possible care. There is also interest in creating a collaborative data-driven approach to innovation that will improve healthcare and develop technical infrastructure.

Social care: Focus will be placed on improving social care data to enable equitable access to information for people in social care settings, allowing for a more personalised treatment whilst taking the pressure off of families to tell their stories multiple times.

National decision-making: National decision-makers will be supported through improved access to data, supporting the planning of national programmes, whilst improving the management of population health and proactive care.

Research: Researchers will have access to data to develop life-changing treatments, diagnostics, models of care and insights.

What does this mean for people living with Inherited Metabolic Disorders (IMDs)?

This plan aims to create a more co-ordinated care system, breaking down barriers to the dissemination of crucial health information, potentially proving invaluable across all aspects of care, research, and decision-making.

Why is this important for me?

Individuals living with Inherited Metabolic Disorders are extremely engaged with health and social care, often accessing a multitude of different services and specialities within care.

Through health and social care services adopting the plan set out in this paper, people affected by IMDs will:

Have a greater understanding of how their data is used.

Benefit from reduced barriers to accessing health data.

Have more direct contact with health care personnel.

Be able to access their own health data, breaking down barriers to their condition and allowing them to take ownership.

Have a more tailored social-care experience.

Have better access to care based on individual needs (e.g., more at risk from lower economic background affected by disparities in care).

Benefit from better research and interventions including medicines, care and technologies including artificial intelligence

Wessex Paediatric Study Day – Metabolic Medicine We were delighted to be invited to present the afternoon session at a Paediatric Study Day in Metabolic Medicine which provided training to the level 2 General Paediatric Trainees in the Wessex region.

We presented the work we do at Metabolic Support UK and shared some statistics from our big survey about the challenges of diagnosis and impact of living with an IMD. As part of the session we also invited 3 speakers to attend on the day, this included Shelby Mutton a parent of a child with OTC, Charlotte Keys, a parent of a child with Citrullinaemia, and Laura Linford a parent of two boys with VLCADD, one who sadly passed away age 2.

Shelby, Charlotte, and Laura all spoke about the route to diagnosis, their experiences of day-to-day management, the impact of living with an IMD, and access to information and support. One of the key themes was the need for progressive awareness and understanding in the healthcare profession. All three parents highlighted in their talks that their child was diagnosed simply because a paediatrician had an inkling the problem may be metabolic, and that inkling essentially saved their child’s life.

We know these very real stories told by the parents themselves make a huge lasting impact on healthcare professionals in their learning and development as such we’d like to say a huge thanks to all our speakers for their passionate and insightful talks and to Katie Restall, Paediatric Trainee for organising this fantastic session.

Please mind the gap...using real world evidence to increase access to innovation What is the real world evidence framework?

This framework aims to resolve gaps in knowledge and increase access to innovations for patients. The framework aims to do so by identifying where realworld data can be used to reduce uncertainties and to improve guidance, whilst describing best practices for conducting, planning and reporting real-world evidence studies to improve the quality and transparency of work.

Example of real-world evidence:

Patient health, experience, or care delivery data collected outside of highly controlled clinical trials. This can include different sources such as health records, surveys, observational cohorts, and other methods of collection

Why it matters to us:

Through utilising real-world data, evidence gaps can be filled to meet the National Institute for Healthcare Excellence (NICE) requirements and as such speeding up patient access. Those developing evidence for NICE guidance and other aforementioned stakeholders will also be better educated, enabling for a better quality of work due to the increase in use of best-practices and transparency whilst addressing risks of bias.

People living with Inherited Metabolic Disorders often have to wait years for new treatments and diagnostics that could potentially improve and save lives. Through filling gaps in evidence and improving processes, it is likely that treatments and diagnostics will become available sooner due to the improvements in the planning, conducting, and reporting of studies. In turn, this will ensure NICE will also become a more informed governing body that can address the needs of patients more effectively due to the data coming from real-world sources.

Know your IMD: CSID What is it?

Congenital sucrase-isomaltase deficiency (CSID) is a genetic condition that affects a person's ability to digest certain sugars.

People with this condition cannot break down the sugars sucrose and maltose.

Symptoms After ingestion of sucrose or maltose, an affected person will typically experience watery diarrhoea, bloating, excess gas production, abdominal pain, and malabsorption of other nutrients. Other symptoms may include nausea, vomiting, or reflux-like symptoms.

In some children, these digestive problems can lead to failure to gain weight and grow at the expected rate (failure to thrive) and malnutrition. Most affected children are better able to tolerate sucrose and maltose as they get older.

Symptoms can vary for a variety of reasons including the timing of introduction of sucrose into a person’s diet, and the amount of sugar and starch consumed.

Infants who are breast-fed or fed lactose-containing formula will often not have symptoms of CSID until they ingest juices, solid foods, or medications that are sweetened by sucrose.

Diagnosis Endoscopic biopsy and laboratory analysis Breath test for sucrose e.g. sucrose breath hydrogen test, carbon-13 breath test Genetic testing

How is CSID treated?

In a person with CSID, dietary restrictions may require life-long adherence to a strict sucrose-free diet. This can vary depending on symptoms, but foods high in sucrose should be avoided.

In the USA an enzyme replacement therapy called sacrosidase (Sucraid) is available, however this is not licensed in the UK. Some patients in the UK may be given a similar version of this which is called Invertase.

How we support the CSID community Metabolic Support UK have joined a community of people living with CSID, aiming to provide care for people affected by the condition whilst keeping them informed about new developments.

We have an ambassador that helps us bridge the gap between patient organisation and the community and we couldn't be more thankful.

Moving forward as we understand more about the lived experience of CSID we'll be able to provide more tailored support whilst empowering the community to act as advocates for their condition at the highest levels.

Stronger Together: Lab. of Inborn Errors of Metabolism (Rio de Janeiro) Patrícia Fernanda Schuck1, Gustavo Costa Ferreira1 Laboratório de Erros Inatos do Metabolismo, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

What a research lab can do for IEM?

The Laboratory of Inborn Errors of Metabolism (LEIM) is a research lab at Universidade Federal do Rio de Janeiro, Brazil. The same way inborn errors of metabolism (IEM) are rare hereditary diseases, also rare are the groups that study them. Our lab aims to understand the alterations that lead to the symptoms in some of these diseases, with emphasis on the cerebral affliction of these patients. Some diseases we are currently investigating include phenylketonuria (PKU), galactosemia, and SLC13A5 epilepsy.

We also consider our mission to contribute to spread the word about these 1000+ inborn errors that have already been identified. Our members are constantly encouraged to participate in events, talks and interviews advocating the importance of raising awareness on these diseases both inside the academia and for the general population. Through our social media we experience rewarding interaction and feedback from foundations, patients, and their families.

In our research on PKU, a disease caused by a failure in the breakdown of the amino acid phenylalanine, we are trying to understand why some neural cells trigger signals to terminate their life cycles in a timeframe shorter than expected (a process called apoptosis). We are also interested in studying cerebellar malfunctioning, a common feature of the galactosemias. The cerebellum is a part of the brain that controls our movements. It is very integrated to the other parts of the brain, and also contributes to some of our intellectual (e.g. language) and emotional (e.g. fear) abilities.

Our goal is to understand how the accumulation of galactose, a sugar from milk, impairs the migration of some brain cells as cerebellum matures. We also study SLC13A5 epilepsy, a form of intractable epilepsy affecting children. People that live with this disease may present over 100 episodes of epilepsy a day, which impacts severely on their quality of life. Our lab studies whether these epilectic crisis depend on the way that nutrients are transferred and utilized in the brain cells, particularly on astrocytes (a cell type named after its star shaped form, which means “star cells” in Greek).

All of these processes alter brain function and often impact the ability of patients with these rare diseases to perform daily activities, socialise and ultimately live well. By gathering information from all available sources (patients' samples, basic research and computational models) to understand why brain cells are not working properly, we can seek ways to improve the therapeutic approach for at least some of these IEM. Sadly, finding a cure is yet a distant hope for most of these diseases. But improving the quality of life of each of these patients is something that our generation can and must attend urgently.

Our team embraces researchers with diverse backgrounds, such as pharmacists, nutritionists, biomedical scientists, biologists and physicians. It is a multidisciplinary joint effort from 20+ researchers (including Faculty, postdocs, MSc and PhD students, and undergrads) working on a daily basis to challenge and publicize the unknowns in the field. Together with our national and international collaborators, we just cannot settle our minds with the idea that there is no satisfactory help for so many children and families living with these devastating diseases.

Every individual is rare. Together we get stronger. That is our motto.

Keiron's story: Citrullinaemia Hi, I'm Tori. My son, Keiron, lost his life to the complications of Citrullinaemia in April 2007.

He was a beautiful healthy bouncing baby boy... or so we thought. He passed all his tests in the hospital with flying colours and we were sent home the next day to begin our journey as a new family.

Sadly, in the next hours Keiron became very unwell. Despite making a number of calls through the night and the next morning to the midwives, who assured me time and time again that he was crying because he's a baby, I knew in my heart that something wasn't right.

So I took him to the hospital regardless. Our nightmare soon began. Keiron was diagnosed with Citrullinaemia, and although he fought so hard, he sadly passed away at 17 days old in my arms after being taken off his life support machine.

Keiron didn't die of Citrullinaemia, he died because of the complications of it, by ammonia levels getting so high in his blood he was brain damaged. After surviving a dialasis machine to replace his poisoned blood and spending 17days fighting this evil disorder, he was declared brain dead. It was recommended that we let him die peacefully in my arms rather than die hooked up to a machine that would eventually flat line.

I hate that this happened to him.

I hate that we didn't know that he had this disorder and that he potentially could have lived a normal, healthy life, had we have known. Had we have had genetic testing we could have saved his life by operating on him and giving him the medication that he needed .

Had we have been prepared for his illness, we could have prevented the damage from happening at all!

After Keiron had survived the dialasis machine, he woke up and breathed all by himself. He cried, filled nappys and responded to our voices as if he'd never been poorly!! He was given a sugar diet and fluids and we were sent to a different ward of the hospital where we spent the night with him, expecting him to recover and be able to come home with us.

The ICU department staff were amazing. They were helpful and empathetic the whole time with myself and my family but unfortunately they didn't know about Citrullinaemia.

The consultants decided that they would slowly introduce protein again. This sent Keiron into a seizure the same evening and he became unresponsive. He was rushed back to the ICU and put back onto the life support machine. He never recovered.

He could have had the operation and medication before they gave him the protein again.

He could be alive now. I will never understand why this happened. But it did, and if I can be a voice that helps this not happen to other families, then I will do what ever i can to help.

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Get involved Metabolic Support UK couldn't exist without you and we aim to do even more in the future to ensure anyone affected by an Inherited Metabolic Disorder is seen, heard and supported.

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