Table 3 Causes of congenital neutropenia
ClassificationConditionDetails
Immune mediatedNeonatal allo-immune (NAIN)

  • Maternal neutrophil specific antibodies

  • Infections rarely severe

  • Average age of recovery is 11 weeks

Primary auto-immune neutropenia

  • No treatment is usually necessary

  • Neutrophil specific auto-antibodies

  • Severe neutropenia but few severe infections

  • Spontaneous recovery in 95% (17 months)

  • G-CSF may be necessary if infection severe

GeneticSevere congenital neutropenia (Kostmann syndrome)

  • Autosomal recessive, autosomal dominant or sporadic

  • Presents in infancy with severe neutropenia and infection

  • Bone marrow shows maturation arrest at the promyelocyte/myelocyte stage.

  • Treat with lifelong G-CSF and antibiotics

  • Risk of malignant transformation (12%)

Cyclical neutropenia

  • Autosomal dominant

  • 21 day cycle of neutropenia (3–5 days)

  • Presents with recurrent fever, mouth ulcers and respiratory symptoms

  • No increased risk of malignancy

  • Responds well to G-CSF

Rarer causesShwachman-Diamond

  • Autosomal recessive

  • Neutropenia, skeletal abnormalities and exocrine pancreatic insufficiency

Glycogen storage disease 1b

  • Mechanism neutropenia unclear

  • Treat with lifelong G-CSF

Wiskott-Aldrich (with WASp activating mutatons)

  • X-linked

  • Combination eczema, neutropenia and thrombocytopaenia

CD40 ligand deficiency

  • X-linked

  • High IgM, low IgG and IgA, neutropenia

  • Recurrent infections and autoimmune disease

Pearson’s syndrome

  • Caused by mitochondrial DNA deletions

  • Refractory sideroblastic anaemia, neutropenia, thrombocytopaenia and exocrine pancreatic failure

Barth syndrome

  • X-linked

  • Mutation in G4.5 gene which encodes for a protein involved in cardiolypin biosynthesis

  • Associated with cardiomyopathy

  • Requires early treatment with G-CSF

Cartilage hair hypoplasia

  • Autosomal recessive

  • Short stature, sparse hair, neutropenia and anaemia

IdiopathicIdiopathic neutropenia

  • Diagnosis of exclusion

  • Few infections and good response to G-CSF

  • No risk of malignant transformation