bjh 2025)

Intro

Common cause of lower neutrophil counts often seen in people of (not exclusively) African/Caribbean ethnicity

Approx. 20% of Duffy-nul individuals will have a neutrophil count <2.0, compare to approx. 1% of Duffy-positive

Asymptomatic finding, not associated with increased risk of infection

Terminology/Synonyms

Duffy null-associated neutrophil count (DANC)

ACKR1/Duffy Associated Neutropenia (ADAN)

(Historically referred to as Benign Ethnic Neutropenia (BEN))

Physiology

ACKR1 (Atypical Chemokine Receptor 1) gene codes for the Duffy blood group

Duffy is expressed by erythrocytes

Duffy regulates chemokine availability by acting as a reservoir for chemokines —> reducing/modulating chemokine concentration in the blood stream

N.B. much more detail on the many functions of Duffy available in the BJH review.

ACKR1 mutation

Homozygous ACKR1 mutation = “Duffy Null Phenotype”

If ACKR1 is not expressed

Individuals have higher levels of circulating chemokines
—> increase neutrophil migration into tissues —> Reduces circulating numbers but not function
—> Chronic, asymptomatic “neutropenia”

The ACKR1 mutation also confers protection against P. vivax, malaria which may explain its geographical distribution.

Testing

Serological = Fya/Fyb negative on red cell phenotyping

Genetic = ACKR1 mutation (not routinely available on the NHS as of 2025)

Arguments in favour of testing include:

Explain cause of neutropenia and therefore reduce need for other tests
Personalised medicine - e.g. prior to prescribing drugs associated with neutropenia such as chemotherapy, anti-psychotics etc

Other Causes of Congenital Neutropenia

See list of inherited bone marrow failure syndrome on the Aplastic Anaemia page