How should Hermansky‑Pudlak syndrome (HPS) be managed in children?

Management of Hermansky-Pudlak Syndrome in Children

Children with Hermansky-Pudlak syndrome require immediate genetic subtyping to determine prognosis and guide surveillance, with HPS type 2 demanding urgent immunologic monitoring due to risk of fatal hemophagocytic lymphohistiocytosis, while all subtypes need lifelong bleeding precautions and ophthalmologic care. 1, 2

Immediate Diagnostic Confirmation and Subtyping

Genetic testing to identify the specific HPS subtype (HPS1-9) is the critical first step, as this directly determines prognosis, surveillance intensity, and risk stratification. 2 The diagnosis is confirmed by demonstrating absent platelet dense granules on electron microscopy combined with gene sequencing. 1, 3

Key Subtype-Specific Risks:

• HPS-1, HPS-2, and HPS-4: High risk for lethal pulmonary fibrosis (typically manifests third decade) 1, 3, 4
• HPS-2 specifically: Severe neutropenia, immunodeficiency, and risk of accelerated hemophagocytic lymphohistiocytosis (HLH) phase that is fatal without chemotherapy 1, 2
• HPS-3: Granulomatous colitis risk 1

Universal Management for All HPS Subtypes

Bleeding Diathesis Management

• Avoid all antiplatelet agents (aspirin, NSAIDs) and anticoagulants 1, 3
• Desmopressin (DDAVP) is ineffective due to absent platelet dense granules 3, 4
• Platelet transfusions are required for bleeding episodes or before surgical procedures 3, 4
• Counsel families on injury prevention and immediate evaluation of any significant trauma 4

Ophthalmologic Care

• Annual ophthalmology examinations for nystagmus, decreased visual acuity, and photophobia management 3, 4
• Provide UV-protective eyewear and low-vision aids as needed 4

Dermatologic Protection

• Strict sun protection with high-SPF sunscreen and protective clothing due to oculocutaneous albinism 3, 4
• Annual skin cancer screening starting in adolescence 4

Critical HPS Type 2-Specific Management

HPS type 2 requires the most aggressive surveillance due to severe immunodeficiency. 1, 2

Immunologic Monitoring

• Monitor absolute neutrophil counts regularly for severe neutropenia 1, 2
• Assess immunoglobulin levels and consider replacement therapy if hypogammaglobulinemia develops 1, 2
• Immediate evaluation for any fever or infection, with low threshold for empiric antibiotics given defective cellular immunity 1, 2

Accelerated Phase (HLH) Recognition

This is the most critical pitfall to avoid—missing the accelerated phase is fatal. 2

Watch for acute presentation with:

• High fever and toxic appearance
• Lymphadenopathy and hepatosplenomegaly
• Cytopenias beyond baseline neutropenia 1, 2

If accelerated phase develops, initiate standard HLH chemotherapy and immunosuppression immediately—this phase is uniformly fatal without treatment. 1, 2

Pulmonary Surveillance (HPS-1, HPS-2, HPS-4)

Begin baseline pulmonary function testing and high-resolution chest CT in late childhood/early adolescence for subtypes at risk of pulmonary fibrosis. 3, 4

• Annual pulmonary function tests starting around age 10-12 years 4
• High-resolution chest CT every 2-3 years to detect early ground-glass opacities or reticulation 3
• Pirfenidone is the only medical therapy with evidence for slowing progression once pulmonary fibrosis develops 3
• Lung transplantation becomes the definitive treatment for progressive pulmonary fibrosis 3

Gastrointestinal Surveillance

• Monitor for granulomatous colitis symptoms (bloody diarrhea, abdominal pain, weight loss), particularly in HPS-1 and HPS-4 3, 4
• Colonoscopy if symptoms develop 4

Important Clinical Pitfalls

Do not assume normal immune function based on routine screening tests in HPS-2—immunologic abnormalities are variable and may not fully manifest until the accelerated HLH phase. 2 The key distinction is that HPS-2 has profound immunodeficiency requiring infectious disease consultation, while other HPS subtypes do not. 1, 2

Never use DDAVP for bleeding management—it is completely ineffective due to the absent platelet dense granules that characterize HPS. 3, 4

Do not delay genetic subtyping—knowing whether a child has HPS-1, HPS-2, or HPS-4 versus other subtypes fundamentally changes surveillance protocols and family counseling about life expectancy. 2, 3