PYCR2-related microcephaly-progressive leukoencephalopathy

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ORPHA:481152OMIM:616420Q87.8
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Overview

PYCR2-related microcephaly-progressive leukoencephalopathy is a rare inherited brain disorder caused by changes (mutations) in the PYCR2 gene. This gene provides instructions for making an enzyme called pyrroline-5-carboxylate reductase 2, which plays an important role in producing the amino acid proline. When this enzyme does not work properly, it affects how brain cells develop and survive. The disease is also sometimes referred to as hypomyelinating leukoencephalopathy-10 (HLD10). The condition mainly affects the brain and nervous system. Children with this disorder are typically born with a smaller-than-normal head size (microcephaly), and over time the white matter of the brain — the tissue that helps nerve signals travel quickly — breaks down progressively. This is called leukoencephalopathy. As the disease progresses, children experience increasing difficulties with movement, muscle tone, and intellectual development. Key symptoms include intellectual disability, muscle stiffness or weakness, delayed development, and seizures. There is currently no cure for this condition. Treatment focuses on managing symptoms, supporting development, and improving quality of life through therapies such as physical therapy, occupational therapy, and anti-seizure medications when needed.

Key symptoms:

Smaller-than-normal head size (microcephaly) present from birth or developing early in lifeIntellectual disability ranging from moderate to severeDelayed or absent developmental milestones such as sitting, walking, and talkingMuscle stiffness (spasticity) affecting the arms and legsMuscle weaknessSeizuresPoor or absent ability to walk independentlyFeeding difficulties in infancyAbnormal eye movements or vision problemsProgressive worsening of neurological symptoms over time

Clinical phenotype terms (50)— hover any for plain English
CNS hypomyelinationHP:0003429
Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for PYCR2-related microcephaly-progressive leukoencephalopathy.

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No actively recruiting trials found for PYCR2-related microcephaly-progressive leukoencephalopathy at this time.

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No specialists are currently listed for PYCR2-related microcephaly-progressive leukoencephalopathy.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to PYCR2-related microcephaly-progressive leukoencephalopathy.

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Community

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Caregiver Resources

NORD Caregiver Resources

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Social Security Disability

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Questions for your doctor

Bring these to your next appointment

  • Q1.What specific mutations were found in my child's PYCR2 gene, and what do they mean for how severe the disease might be?,Should other family members, including siblings, be tested for this condition?,What therapies do you recommend right now, and how often should my child receive them?,What signs should prompt me to go to the emergency room, and do we need a seizure rescue medication at home?,Are there any clinical trials or research studies that my child might be eligible for?,What specialists should be part of my child's care team, and how often should we see each one?,What can we expect over the next few years in terms of how the disease may progress?

Common questions about PYCR2-related microcephaly-progressive leukoencephalopathy

What is PYCR2-related microcephaly-progressive leukoencephalopathy?

PYCR2-related microcephaly-progressive leukoencephalopathy is a rare inherited brain disorder caused by changes (mutations) in the PYCR2 gene. This gene provides instructions for making an enzyme called pyrroline-5-carboxylate reductase 2, which plays an important role in producing the amino acid proline. When this enzyme does not work properly, it affects how brain cells develop and survive. The disease is also sometimes referred to as hypomyelinating leukoencephalopathy-10 (HLD10). The condition mainly affects the brain and nervous system. Children with this disorder are typically born with

How is PYCR2-related microcephaly-progressive leukoencephalopathy inherited?

PYCR2-related microcephaly-progressive leukoencephalopathy follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does PYCR2-related microcephaly-progressive leukoencephalopathy typically begin?

Typical onset of PYCR2-related microcephaly-progressive leukoencephalopathy is infantile. Age of onset can vary across affected individuals.