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WHIM syndrome

A rare combined primary immunodeficiency disorder often characterized by neutropenia, hypogammaglobulinemia, and high susceptibility to human papillomavirus (HPV) infection.

Prevalence

Global prevalence is unknown

Median Age at Diagnosis

5.5 years*

ICD-10

There is no specific ICD-10 code for WHIM syndrome.

D81.89

(Other combined immunodeficiencies) can be used for reimbursement purposes. Other codes are also used, depending on the clinical presentation.

Inheritance

Autosomal dominant

Individuals with a CXCR4 pathogenic variant have a 50% chance of passing the disease to their offspring.

5 Facts you should know

FACT

1

Genetic Basis and CXCR4 Variants
The CXCR4 pathway is essential for regulating the trafficking of white blood cells between the bone marrow and peripheral blood. In WHIM syndrome, pathogenic CXCR4 variants can impair CXCR4 internalization, causing... Learn more

FACT

2

Early Childhood Onset*
The median age of diagnosis is 5.5 years, but WHIM syndrome often presents earlier, with infections being one of the first manifestations.

FACT

3

Hallmark Features
The 4 manifestations in the WHIM acronym include warts, hypogammaglobulinemia, infections, and myelokathexis. However, not all patients display all 4 signs, with <25% presenting with all 4 features​.*

FACT

4

Neutropenia and Lymphopenia
Neutropenia is the most common laboratory finding (98%). Lymphopenia, another common laboratory finding, affects 88% of patients.*

FACT

5

Susceptibility to Infections
People with WHIM syndrome are prone to recurrent infections. Infections are often the first sign of WHIM syndrome, and serious infections may result in long-term complications such as bronchiectasis and hearing loss.*

WHIM syndrome is also known as...

WHIM syndrome is also known as:

  • Warts, Hypogammaglobulinemia, Infections, and Myelokathexis

What’s your Rare IQ?

All four manifestations in the WHIM acronym are present in fewer than 25% of patients with WHIM syndrome. Which of the following is reported in the fewest patients?

Common signs & symptoms

Frequent infections

Chronic or recurrent warts (an HPV-related manifestation)

Frequent laboratory findings

Neutropenia

Lymphopenia

Hypogammaglobulinemia

Management of WHIM syndrome

Granulocyte Colony-Stimulating Factor (G-CSF)

G-CSF is commonly used to increase neutrophil counts and reduce the frequency of infections. It improves the absolute neutrophil count (ANC) in many patients. It can also reduce infection susceptibility.

Immunoglobulin Replacement Therapy (IgGRT)

This treatment helps to manage hypogammaglobulinemia and reduce infection frequency. It is often used in conjunction with antibiotics to prevent severe infections.

Antibiotic Prophylaxis

Preventive antibiotics are administered to reduce the frequency and severity of infections. This is especially helpful in patients with recurrent bacterial infections.

Hematopoietic Stem Cell Transplantation (HSCT)

HSCT is considered a definitive cure for WHIM syndrome, though data is limited due to the small number of patients with WHIM who have received HSCT.

Supportive Care

Management of infections, autoimmune complications, and monitoring for malignancies (such as HPV-related cancers) are critical aspects of care. Early treatment can help prevent end-organ damage.

Leaving Site Interstitial Learn about an FDA-approved treatment for patients with WHIM syndrome.

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*Much of our current understanding of WHIM syndrome and its manifestations is drawn from from a 2022 study of 66 patients by Geier et al. Generalized statements in this page are based on this cohort of patients and information from the publication cited below.

This WHIM educational page is supported by X4 Pharmaceuticals. This content was developed by Rare Medical News in collaboration with X4 Pharmaceuticals.

X4NM-US-000-2400077 (V1.0) Dec 2024

References:
Geier CB, Ellison M, Cruz R, et al. Disease progression of WHIM syndrome in an international cohort of 66 pediatric and adult patients. J Clin Immunol. 2022;42(8):1748-1765. doi:10.1007/s10875-022-01312-7.​ Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM. WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure. J Clin Immunol. 2019;39(6):532-556. doi:10.1007/s10875-019-00665-w