Overview
H syndrome is a rare autosomal recessive multisystem disorder caused by mutations in the SLC29A3 gene, which encodes the human equilibrative nucleoside transporter 3 (hENT3). The name 'H syndrome' derives from the many clinical features that begin with the letter H. It is characterized by cutaneous hyperpigmentation and hypertrichosis, often distributed in a symmetrical pattern on the inner thighs and lower extremities, along with hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height (short stature), and hallux valgus. Histiocytic infiltration of the skin and other organs is a hallmark pathological finding. H syndrome belongs to a spectrum of SLC29A3-related disorders that also includes Faisalabad histiocytosis, pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) syndrome, and familial Rosai-Dorfman disease, which share overlapping clinical features. The condition typically presents in childhood, with hyperpigmented, indurated skin patches appearing on the medial thighs and gradually spreading. Scleroderma-like skin changes may develop. Systemic manifestations can include insulin-dependent diabetes mellitus, exocrine pancreatic insufficiency, flexion contractures of joints, lymphadenopathy, and variable degrees of intellectual disability. Cardiac involvement may include cardiomyopathy or valvular abnormalities. The histiocytic infiltrates found in affected tissues consist of CD68-positive, S100-negative histiocytes, distinguishing them from Langerhans cell histiocytosis. There is currently no specific or curative treatment for H syndrome. Management is supportive and multidisciplinary, addressing individual symptoms as they arise. This may include insulin therapy for diabetes, hearing aids for sensorineural hearing loss, orthopedic interventions for skeletal deformities, and dermatological management for skin manifestations. Regular monitoring by a team including endocrinologists, cardiologists, dermatologists, and audiologists is recommended. The prognosis varies depending on the severity and range of organ involvement.
Clinical phenotype terms— hover any for plain English:
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Childhood
Begins in childhood, roughly ages 1 to 12
FDA & Trial Timeline
10 eventsFudan University — PHASE2
GlaxoSmithKline — PHASE1, PHASE2
GERCOR - Multidisciplinary Oncology Cooperative Group — PHASE2
Nanjing First Hospital, Nanjing Medical University — NA
Rabin Medical Center
Cairo University — NA
Sun Yat-sen University — PHASE1, PHASE2
AIO-Studien-gGmbH — PHASE2
Duk-Woo Park, MD — PHASE4
West China Hospital — PHASE1, PHASE2
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
No FDA-approved treatments are currently listed for H syndrome.
1 clinical trialare actively recruiting — trials can provide access to cutting-edge therapies.
View clinical trials →Rare Disease Specialist
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to H syndrome.
Community
No community posts yet. Be the first to share your experience with H syndrome.
Start the conversation →Latest news about H syndrome
Disease timeline:
New recruiting trial: Cadonilimab for PD-1/PD-L1 Blockade-refractory, MSI-H/dMMR, Advanced Colorectal Cancer
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: Sintilimab Plus Hypofractionated Radiotherapy for MSI-H/dMMR Rectal Cancer
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: A Study to Assess the Safety, Tolerability, and Efficacy of NDI-219216 in Patients With Advanced Solid Tumors.
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: A Study to Investigate the Safety and Preliminary Efficacy of GSK5460025 Alone or in Combination With Other Anti-cancer Agents in Participants With Solid Tumors
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: Potassium-Competitive Acid Blocker Versus pROton-Pump Inhibitor for GastroproTECTion Strategies In Patients at High Gastro-Intestinal Bleeding Risk Receiving Antithrombotic Therapy
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: Assessing the Association Between H. Pylori Persistence and the Severity of Insulin Resistance in Patients With Metabolic Syndrome
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: Effect of Combined Lumbar Traction and Repetitive Back Extension Exercise on H-reflex in Lumbosacral Radiculopathy
A new clinical trial is recruiting patients for H syndrome
New recruiting trial: Neoadjuvant Toripalimab With or Without Celecoxib in dMMR/MSI-H Colorectal Cancer
A new clinical trial is recruiting patients for H syndrome
Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Common questions about H syndrome
What is H syndrome?
H syndrome is a rare autosomal recessive multisystem disorder caused by mutations in the SLC29A3 gene, which encodes the human equilibrative nucleoside transporter 3 (hENT3). The name 'H syndrome' derives from the many clinical features that begin with the letter H. It is characterized by cutaneous hyperpigmentation and hypertrichosis, often distributed in a symmetrical pattern on the inner thighs and lower extremities, along with hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height (short stature), and hallux valgus. Histiocytic infiltration of the skin and other organs
How is H syndrome inherited?
H syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does H syndrome typically begin?
Typical onset of H syndrome is childhood. Age of onset can vary across affected individuals.
Are there clinical trials for H syndrome?
Yes — 1 recruiting clinical trial is currently listed for H syndrome on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat H syndrome?
22 specialists and care centers treating H syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.