This Family Route Map is a guide to current UK services and information.
This article is designed to provide signposts to sources of current information and appropriate services for patients, their families and carers, together with healthcare professionals. The first version of this guide was published in 2009 for XLP1 and this latest version (v3) was published in November 2023 and has been extended to include XIAP. This guide will help you find the key information you need about X-linked Lymphoproliferative syndrome quickly and easily.
The following hospitals are the key centres for specialist support for XLP1 and XIAP. The links below will take you to the relevant immunology department.
Great Ormond Street Hospital - London
Great North Children's Hospital - Newcastle
Living with a long-term condition requiring frequent hospital visits or admission for check-ups or treatment can put a strain on finances. Citizens Advice can help with advice locally about benefits and we like this web site put please note that there is a subscription charge: www.benefitsandwork.co.uk.
Psychological counselling is not commonly offered on diagnosis or even later on. If you feel that you need extra help in coming to terms with your condition or any other aspect of your life, don’t be afraid to ask for this via your GP or immunology specialist.
It is common to have difficulties finding adequate and affordable insurance policies once you have a pre-existing condition. We recommend that you undertake a Google search for insurers that cover rare conditions - there are many.
Say how you feel: if you don’t want medical students participating in your appointments; or clinical staff discussing your child in front of them, don’t be afraid to say so.
X-linked lymphoproliferative syndrome (XLP), is a rare set of diseases that manifest themselves in boys. To date only about 200 families and 600+ boys have been diagnosed worldwide. It is likely, however, that there are many more cases where the correct diagnosis has not been made.
XLP1 can have many symptoms including: severe glandular fever, cancer of the blood (lymphoma) and inability to fight off infections and sometimes severe anaemia. 70% of boys with XLP die by the age of 10 years without any treatment. The cause of the condition was only found in 1998 so there is still a lot to learn. Research into XIAP (XLP2) is very much in it's infancy. We still have a lot to learn.
The best ‘prevention’ is regular top ups of anti-viral medicines, immunoglobulin therapy or steroids, but these are not a cure. Today the only possible cure is a bone marrow transplant, in effect replacing the faulty immune system.
If XLP1 or XIAP is suspected, then the boy should be referred to an immunology specialist. They will be able to arrange for a genetic test. As XLP1 is an inheritable condition, other family members will be offered predictive gene testing if XLP1 or XIAP is diagnosed.
There are a number of issues surrounding genetic testing particularly in relation to children and as such, many patients may wish to be seen and counselled by a consultant clinical geneticist as early on as possible. It is also possible that an affected family could see a Genetic Councillor for more support - this can usually be arranged via your immunology team.
The following web pages from the NHS is well worth spending some time reading, covering genetic testing, genetic counselling and the potential impact on your family.
The diagnosis of XLP1 is suspected in males who have a severe, abnormal immune system response to infection with Epstein-Barr virus (EBV). EBV is a common virus in the normal population, which causes infectious mononucleosis (glandular fever). In normal males, EBV causes no long lasting ill effects. In males with XLP1, there is a mutation (mistake) in the XLP SH2D1A/DSHP/SAP gene. These genes helps control the immune response to an EBV infection and codes for the SAP protein. As a result, males with XLP who are exposed to the EBV virus can have life-taking threatening symptoms. Patients can experience swollen lymph nodes (glands in the neck or groin), sore throat, fever, and severe hepatitis. After infection with EBV, some patients develop aplastic anaemia (low levels of all types of blood cells) and hypogammaglobulinemia (low levels of anti- bodies in the bloodstream), Severe symptoms occur because the immune system cannot effectively handle the EBV as in normal individuals and can include severe glandular fever and lymphoma.
Most XIAP affected boy develop HLH related to EBV infection (also referred to as VAHS) but in some cases they show HLH without having EBV as the obvious trigger. Typical symptoms of HLH besides persistent fever are pallor (paleness), jaundice, liver and spleen enlargement, and neurological symptoms, such as irritability or even seizures. In males with XIAP, there is a mutation (mistake) in the BIRC4 gene.
The diagnosis will be suggested by the pattern of illness in the child and their family. In most children XLP can be confirmed using a blood test. This will check if the relevant protein, that makes the cells work properly is present, and will also look for the mistake in the gene. In some families there may not be a mistake in these particular genes, and the diagnosis can be made on the clinical story only.
Initially treatment will be given for the symptoms that the boy presents with, this may include anti-viral medicines, immunoglobulin therapy and/or antibiotics. These will be given to keep them well in the short to medium term. Bone marrow transplant is the definitive treatment of choice at the present time, This can be a difficult procedure, requiring a prolonged hospital stay and can present its own particular risks.
More general information can be found on the following websites:
PubMed
PubMed is a service of the U.S. National Library of Medicine and the National Institute of Health and is free to join after registration. Search for ‘XLP’ 'XLP1' or 'XIAP' and a comprehensive list of worldwide medical research papers on XLP is returned.
Orphanet
European website providing extensive information on rare diseases including XLP1 and XIAP.
European Society for Immunodeficiencies (ESID)
ESID is a non for profit association that was created in 1994. ESID has been striving to improve the knowledge in the field of Primary Immunodeficiency (PID) by encouraging research, developing educational programs and fostering cooperation among all those involved in the diagnosis, treatment and management of these diseases.
Genomics England - The Generations Study
In October 2023 it was announced that XLP1 and XIAP will be part of the 'Generation Study' within the NHS to explore the benefits, challenges and practicalities of sequencing and analysing newborns' genomes. The program is expected to start late in 2023.
The National Organization for Rare Diseases (NORD)
A US based nonprofit, NORD is dedicated to individuals with rare disease.
It is good to think through the key questions you have for your medical team. Write down your questions in advance of a meeting.
Version 3.0. Date published: November 2023.
This leaflet has been prepared in good faith to provide patients with a guide to current services and information. The XLP Research Trust can be held responsible for the accuracy of the information it contains. Links to other organisations are included for information purposes only and are not recommendations from The XLP Research Trust.
The XLP Research Trust was founded in the UK by David and Allison Hartley who have four sons with XLP. Official charity status was granted in September 2005.
The main aims and objectives are to:
We would like to thank the Genetic Interest Group (GIG) who produced the template for this route map. Unfortunately GIG is no longer operational. The Family Route Maps project was originally funded by the charity Jeans for Genes and an unrestricted educational grant from Genzyme Therapeutics Ltd.
