The Yaya Foundation for 4H Leukodystrophy
Cycle 1
4H Leukodystrophy is a rare disease of the central nervous system. The name 4H stands for Hypomyelination, Hypogonadotropic Hypogonadism and Hypodontia. The disease is also known as POLR3-Related Leukodystrophy or 4H Syndrome. Leukodystrophy disease affects the white matter of the brain and damages the myelin sheath, which surrounds and protects the nerve cells in the brain and spinal cord and assists with transmission of messages between cells. Hypomyelination, hypodontia, and hypogonadotropic hypogonadism are common signs of leukodystrophy disease.
Last updated 04/30/2025
Clinical
Disease Class
Endocrine diseases
Genetic diseases
Neurological diseases
Body Systems
Digestive
Endocrine
Muscular / Skeletal
Nervous / Sensory
Reproductive
Respiratory
Organs
Brain
Ductus deferens
Eyes
Fallopian tubes
Mouth / teeth
Ovaries
Penis
Prostate gland
Scrotum
Testes
Thyroid
Uterus
Known Genetic Link
Yes, one or more genes directly cause the condition
causative_genes
POLR1C
POLR3A
POLR3B
POLR3D
POLR3K
contributory_genes
None specified / unknown
Type of Inheritance
Autosomal recessive
Newborn Screening
No
Disease Mechanism(s)
Myelination defect
Pathogenic mutation
Age of Onset
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Infancy (age 0-1)
Middle childhood (6-11)
Average Age at Diagnosis
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Infancy (age 0-1)
Middle childhood (6-11)
Life Expectancy
Adolescence (12-17)
Adulthood (age 18-64)
Early childhood (age 1+-5)
Affected Sex(es)
Female
Male
National Prevalence
101-1000
Global Prevalence
Unknown
National Incidence
Less than 10
Global Incidence
Less than 10
Populations and/or ancestry with higher prevalence
Known founder mutation in French Canadians. Potential founder mutations in Algeria and Tunesia. Otherwise unknown.
Symptoms / Phenotypes
abnormality of the dentition
atypical puberty
balance problems
breathing difficulties
cognitive decline
craniofacial abnormalities
developmental delay
dysphagia
growth delay / deficiency
joint pain / arthralgia
movement disorders / ataxia / tremor
muscle stiffness
vision problems
Biomarkers
Diagnostic
· MRI (brain), mutation analysis
Existing Therapies
None
Organizational & Research
Cell Lines
None
Cell Lines, Institution
None
Cell Lines, share
N/A
Disease Model
Mouse
Disease Model, Involvement
Funded
Disease Model, share
Unsure
Clinical Trial Role
Not involved
Biobank, Institution
None
Center of Excellence, Institution
None
Registry
Yes, we have collaborated on a registry
Data Collected, Registry
Genetic data
Patient contact info
Patient-reported data
Data Entered by, Registry
Patients
Platform, Registry
RARE-X
Natural History Study
Yes, we have collaborated on a natural history study
Data Collected, Natural History Study
Genetic data
Imaging data
Prospective data
Retrospective data
Platform, Natural History Study
Other
REDCap
FDA Patient Listening Session
No
FDA Patient-Focused Drug Development (PFDD) Program
No
ICD Codes
Yes, we have an ICD-10 code specific to our exact disease
Diagnostic Guidelines
No
Science Advisory Board Policies
No policies
Research Network Policies
Does not have a CRN
Research Roadmap
Yes we have a Research Roadmap, and will share policies
International Chapters
None
International Partners
Europe