Patient Led Research Hub

Gastrointestinal & urinary issues in Pitt Hopkins sydrome

Pitt-Hopkins syndrome (PTHS) is an ultra-rare genetic condition, often presenting with a cluster of symptoms thought to be caused by an underlying dysregulation of the autonomic nervous system. We first collaborated with Pitt Hopkins UK in 2019, helping them establish a family registry and conducting an online survey to gather lived experiences from PTHS families affected by breathing anomalies. Now, Pitt Hopkins UK are keen to expand these efforts by understanding lived experiences of gastrointestinal and urinary issues.

Supported by a pro-bono team, including a specialist dietician, gastroenterologist, PTHS clinical expert, and qualitative researchers, we have composed a detailed online survey aiming to:

1) understand the prevalence and severity of gastrointestinal and urinary issues;
2) explore patterns between these issues and episodes of hyperbreathing;
3) understand the impact this cluster of symptoms has on quality of life.

We have secured ethics approval and data transfer agreements, and look forward to launching the survey later this year.

Treating TANGO2 with vitamin B5

TANGO2 deficiency is an ultra-rare genetic condition that can cause serious metabolic crises, muscle breakdown, heart rhythm problems, and learning difficulties. There is no specific treatment, with clinical care aiming to manage symptoms as they appear. However, a recent natural history study and pre-clinical work in fruit flies and human cells, have begun to evidence the benefit of vitamin B5 (pantothenic acid) in restoring healthy function, as it helps the body produce coenzyme A which is essential for energy production and fat metabolism.

Many families have decided to use vitamin B5 supplements for their children with TANGO2, with widespread improvements in energy, fewer crises, and better general health. TANGO2UK are keen to clinically evaluate these anecdotal reports to understand safety, inform dosage from infancy, and encourage prescription. Ideally this work will also contribute to TANGO2’s inclusion within NHS newborn screening, ensuring effective treatment from birth and improved lifelong outcomes.

Clinical presentations of CASK gene mutations

CASK-related disorders are ultra-rare neurodevelopmental conditions with a broad range of symptoms caused by variations in the type of genetic mutation and mosaicism. Most cases reported in medical literature describe non-verbal individuals with complex and severe symptoms, and poor quality of life with limited independence. Milder cases are likely under-reported, as affected individuals often require less clinical support and may not come to medical attention.

CASK Research aims to support their families by presenting a clear picture of CASK-related disorders and the range of potential symptoms. Of particular importance to the charity is documenting communication, emotional and social behaviours, expanding a 2025 publication ‘The neurodevelopmental spectrum of CASK-related disorder‘ co-authored by CASK Research and geneticists at the University of Cambridge. As a first step, we are reviewing published literature and exploring the patient-reported RARE-X database.

Neurological consequences in Congenital Hyperinsulinism

Congenital Hyperinsulinism (CHI) is a rare but serious condition that affects how the body regulates blood sugar. It is the most common cause of persistent hypoglycaemia in infants and children and a major cause of hypoglycaemic brain injury. CHI families are keen to understand which brain areas are the most affected and the potential correlation with other neurodevelopmental disorders. They are concerned about the long-term neurological consequences associated with hyperinsulinism, particularly as accessing appropriate and timely clinical care, including support for children in education, is difficult and highly varied across the UK.

To begin improving the care pathway for children with CHI, we first need to understand the existing process for neurodevelopmental assessment, referral, and treatment across the UK. Led by the Children’s Hyperinsulinism Charity, we’ve teamed up with paediatric clinicians, specialist nurses, and educational psychologists to design a project which maps existing NHS service provision and creates consensus-based care guidelines. We submitted our Stage 1 funding application to NIHR’s Research for Patient Benefit in July, and look forward to the outcome later this year.

Drug repurposing in Idiopathic Hypersomnia

Idiopathic hypersomnia (IH) is sleep disorder characterised by excessive daytime sleepiness, sleep drunkenness (difficulties waking from sleep), and brain fog. IH significantly affects quality of life for patients and their loved ones; it is difficult to reliably diagnose and there are no disease-specific treatments. Hypersomnolence UK, along with European colleagues, are keen to explore the potential of repurposing an existing adenosine antagonist medication as a new IH treatment.

We’ve developed this proposal with sleep and respiratory consultants, reviewed existing patient-reported datasets, and completed a UK-based patient survey. In 2025, we applied to the Medical Research Council for trial funding. While unsuccessful, we have since worked hard with Papworth Trials Unit Collaboration and the LifeArc Centre for Acceleration of Rare Disease Trials to improve our design and address reviewer comments. We’ve refined our proposal to conduct a cross-over randomised clinical trial, including exploratory blood biomarkers, and have applied to LifeArc’s Rare Disease Clinical Trials Programme. We look forward to the outcome later this year.

Breathing abnormalities in Pitt Hopkins syndrome

Pitt-Hopkins syndrome (PTHS) is an ultra-rare condition caused by a genetic mutation on chromosome 18. PTHS is associated with characteristic physical features, developmental delay and learning difficulties. Many patients also experience frequent episodes of hyper-breathing and/or apnoea. Pitt Hopkins UK is interested in learning more about these breathing anomalies: why do they affect only some people, what are the long-term consequences, and how can they be treated?

Pitt Hopkins UK and the PLRH have teamed up with geneticists and respiratory researchers in Cardiff, Bristol, and Exeter to look into these symptoms. We composed an online survey to capture lived experiences, and were very pleased to have nearly 100 responses from families and carers. These results helped us identify how a wearable breathing sensor might work, which we further explored with textile engineers. We also expanded our team to include Rett UK, a patient charity for Rett syndrome who share similar breathing concerns. Together, we successfully secured UKRI Impact Acceleration funding from the University of Exeter to develop a prototype and user-test with PTHS and Rett syndrome families. We are delighted at this outcome, and look forward to supporting the project over the next year.