Histiocytosis lymphadenopathy plus syndrome, also known as SLC29A3 spectrum disorder is characterised by the overgrowth of immune cells known as histiocytes (macrophage and dendritic cells).^1-5 This overgrowth is due to genetic changes in the SLC29A3 gene. The histiocytes accumulate in tissues in the body, leading to tissue or organ damage. Histiocytosis lymphadenopathy plus syndrome can affect many parts of the body, resulting in a wide range of symptoms.^4,6,7

Historically, there are four different histiocytic conditions described in the literature (as listed below); however, as these conditions share the same genetic cause and have overlapping symptoms, they are now considered to be histiocytosis lymphadenopathy plus syndrome:^1,2,4,6

• Faisalabad histiocytosis (FHC)
• H syndrome
• Pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID)
• Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease

Synonyms: SLC29A3 spectrum disorder.^1,6

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:168569 H syndrome

ICD-11: LD27.Y Other specified syndromes with skin or mucosal anomalies as a major feature

Symptoms and severity of histiocytosis lymphadenopathy plus syndrome can vary widely between individuals.^4,7

Common symptoms may include:^4,6-8

• Patches on the skin with hyperpigmentation and excessive hair growth (hypertrichosis), commonly on the trunk and lower limbs
• Skin changes such as thickening and hardening of the skin
• Hearing loss
• Short stature
• Swollen lymph nodes
• Enlarged liver and spleen
• Hypogonadism (low levels to no sex hormones which can affect puberty, growth, and reproductive functions)
• Joint deformities such as bending of fingers that cannot be straightened

Histiocytosis lymphadenopathy plus syndrome can also affect other parts of the body such as the heart, eyes, kidneys, central nervous system, distinctive tracts, endocrine system, and others.^1,3,4,6

Please speak to your medical team to learn more about the symptoms and complications of a specific type of histiocytosis lymphadenopathy plus syndrome.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Histiocytosis lymphadenopathy plus syndrome is caused by disease-causing genetic changes (variants) on the SLC29A3 gene on chromosome 10.^2,6

All individuals have two copies (alleles) of the SLC29A3 gene – one on each chromosome that is inherited from each parent. Histiocytosis lymphadenopathy plus syndrome are autosomal recessive conditions, which means that both copies of the SLC29A3 gene must have the disease-causing genetic variants.^2,6,8

The genetic variant can be inherited, which means it can be passed on to the next generation. Individuals with the genetic variant in only one copy are unaffected, but will be a carrier and may pass on that variant to their children. If both parents are carriers (each have a copy of the disease-causing variant), there is a 25% chance the child will inherit both disease-causing variants and have histiocytosis lymphadenopathy plus syndrome.⁸ More information on autosomal recessive inheritance pattern can be found at Centre for Genetics Education: Autosomal recessive inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of histiocytosis lymphadenopathy plus syndrome may be made based on:^1,8

• Physical examination
• Blood tests which may show high erythrocyte sedimentation rate (suggesting inflammation in the body), mild anaemia (low red blood cell count), higher liver enzymes (suggesting the liver may be under stress), and high level of antibodies.¹
• Skin biopsy to look for histiocytes accumulation
• Genetic testing showing SLC29A3 gene variant

As part of the diagnosis process, doctors may rule out other conditions that have similar symptoms (differential diagnosis), such as Torg-Winchester syndrome, haemochromatosis, POEMS syndrome and Rosaï-Dorfman disease.^1,8

Please speak to your medical team to learn more about the available pathways for diagnosis of a specific type of histiocytosis lymphadenopathy plus syndrome.

There is currently no curative treatment for histiocytosis lymphadenopathy plus syndrome. Treatment is targeted at managing symptoms and involves a multidisciplinary care team. This may include:^1,8

• Laser therapy to manage excessive hair growth
• Corticosteroid to improve skin changes
• Immunomodulating agents to reduce inflammation

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of individuals with histiocytosis lymphadenopathy plus syndrome may include general practitioners (GP), ear nose throat (ENT) specialist, endocrinologists, dermatologists, and clinical geneticists.⁴ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for histiocytosis lymphadenopathy plus syndrome in Australia or internationally. If you know of any relevant care guidelines, please let us know via the Contribute page.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

Australian Organisation:
We are not aware of any rare disease organisations for histiocytosis lymphadenopathy plus syndrome in Australia. If you are aware of any relevant Australian organisations, please let us know via the Contribute page.

International Organisation:
Histiocytosis Association (United States of America)
Website: https://histio.org/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Histiocytosis lymphadenopathy plus syndrome varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on histiocytosis lymphadenopathy plus syndrome can be found at:

• MedLine Plus: Histiocytosis-lymphadenopathy plus syndrome
• Genetic and Rare Diseases (GARD) Information Center: H syndrome

Online Mendelian Inheritance in Man, OMIM^®:#602782 Histiocytosis-lymphadenopathy plus syndrome

Orphanet: H syndrome

Human Phenotype Ontology (HPO): Histiocytosis-lymphadenopathy plus syndrome

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.