Primary hemophagocytic lymphohistiocytosis with hypopigmentation

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Overview

Primary hemophagocytic lymphohistiocytosis (HLH) with hypopigmentation is a group of very rare inherited immune disorders that combine two main problems: a severely overactive immune system and lighter-than-expected skin, hair, or eye color (hypopigmentation). In these conditions, certain immune cells (macrophages and lymphocytes) become abnormally activated and begin attacking the body's own healthy cells and tissues, a process called hemophagocytosis. This leads to high fevers, enlarged liver and spleen, low blood counts, and potentially life-threatening organ damage. At the same time, the genetic defects responsible also affect the way pigment is made or distributed in the body, causing partial albinism or unusually light coloring. This group includes several specific syndromes such as Griscelli syndrome type 2, Chediak-Higashi syndrome, and Hermansky-Pudlak syndrome type 2. Each is caused by mutations in different genes, but they share the hallmark combination of immune dysregulation and pigment abnormalities. Symptoms typically appear in infancy or early childhood and can progress rapidly. Without treatment, the immune overactivation (HLH episodes) can be fatal. The main curative treatment is hematopoietic stem cell transplantation (bone marrow transplant), which can correct the immune defect. Before transplant, patients usually receive chemotherapy and immunosuppressive medications to control the overactive immune response. Early diagnosis and prompt treatment are critical for improving outcomes.

Also known as:

Key symptoms:

Unusually light skin, hair, or eye color (partial albinism)Silvery-gray hairProlonged high feversEnlarged liverEnlarged spleenLow red blood cell counts (anemia)Low platelet counts causing easy bruising or bleedingLow white blood cell counts leading to frequent infectionsSwollen lymph nodesSkin rashesJaundice (yellowing of skin or eyes)Neurological problems such as seizures or developmental delaysFatigue and irritabilityPoor feeding in infantsRecurrent or severe infections

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 ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Primary hemophagocytic lymphohistiocytosis with hypopigmentation.

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No actively recruiting trials found for Primary hemophagocytic lymphohistiocytosis with hypopigmentation at this time.

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No specialists are currently listed for Primary hemophagocytic lymphohistiocytosis with hypopigmentation.

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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

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.Which specific genetic subtype does my child have, and what does that mean for their outlook?,How soon should we plan for a bone marrow transplant, and how do we find a suitable donor?,What are the warning signs of an HLH flare that I should watch for at home?,Are there any clinical trials or new treatments available for this condition?,What neurological complications should we watch for, and how are they monitored?,Should other family members be tested to see if they carry the gene mutation?,What support services are available for our family, including developmental and psychological support?

Common questions about Primary hemophagocytic lymphohistiocytosis with hypopigmentation

What is Primary hemophagocytic lymphohistiocytosis with hypopigmentation?

Primary hemophagocytic lymphohistiocytosis (HLH) with hypopigmentation is a group of very rare inherited immune disorders that combine two main problems: a severely overactive immune system and lighter-than-expected skin, hair, or eye color (hypopigmentation). In these conditions, certain immune cells (macrophages and lymphocytes) become abnormally activated and begin attacking the body's own healthy cells and tissues, a process called hemophagocytosis. This leads to high fevers, enlarged liver and spleen, low blood counts, and potentially life-threatening organ damage. At the same time, the g

How is Primary hemophagocytic lymphohistiocytosis with hypopigmentation inherited?

Primary hemophagocytic lymphohistiocytosis with hypopigmentation follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Primary hemophagocytic lymphohistiocytosis with hypopigmentation typically begin?

Typical onset of Primary hemophagocytic lymphohistiocytosis with hypopigmentation is infantile. Age of onset can vary across affected individuals.