IllnessNeutropenia, cyclic; differential diagnosis

NGS +

Cyclic neutropenia causes frequent infections due to the lack of neutrophil granulocytes starting at birth or shortly thereafter. In most affected individuals, neutropenia occurs every 21 days and lasts about 3-5 days. The patients typically develop recurrent sinus infections, respiratory skin infections, ulcers of the mouth and colon, pharyngitis and gingivitis, recurrent fever or abdominal pain. When neutrophil levels are normal during the interval, there is no increased risk of infection or inflammation. The differential diagnosis for non-syndromal neutropenia mainly includes ELANE-related neutropenia, then also Kostmann disease, G6PC3 deficiency, GFI1-related severe congenital neutropenia and benign ethnic neutropenia. Selected syndromes with congenital neutropenia include glycogen storage disease (type Ib + Ic), Shwachman-Diamond syndrome, cartilage-hair hypoplasia, Chediak-Higashi syndrome, Griscelli syndrome 1-3, Barth syndrome, Wiskott-Aldrich syndrome, dyskeratosis congenital and myelocathexis. Classic ELANE-related neutropenia is inherited in autosomal dominant manner, whereas the diseases of relevance in the differential diagnosis are often inherited in autosomal recessive and rarely in an X-linked manner. In patients with a clinical diagnosis of cyclic neutropenia, ELANE mutations were detected in approximately 90% of cases. However, a negative molecular genetic result cannot exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1533/

• Allelic: Aplastic anemia, susceptibility to (SBDS)
• Allelic: Blood group, Duffy system ACKR1)
• Allelic: Cartilage-hair hypoplasia (RMRP)
• Allelic: Deafness, AD 34, with/-out inflammation (NLRP3)
• Allelic: Deafness, AD 37 (COL11A1)
• Allelic: Fibrochondrogenesis 1 (COL11A1)
• Allelic: Lumbar disc herniation, susceptibility to (COL11A1)
• Allelic: Malaria, vivax, protection against (ACKR1)
• Allelic: Metaphyseal dysplasia without hypotrichosis (RMRP)
• Allelic: Mevalonic aciduria (MVK)
• Allelic: Multiple sclerosis, susceptibility to, 5 (TNFRSF1A)
• Allelic: Neutrophilic dermatosis, acute febrile (MEFV)
• Allelic: Porokeratosis 3, multiple types (MVK)
• Allelic: Stickler syndrome, type II (COL11A1)
• Allelic: Thrombocytopenia with beta-thalassemia, XL (GATA1)
• Allelic: Thrombocytopenia, XL (WAS)
• Allelic: Thrombocytopenia, XL, intermittent (WAS)
• Allelic: Thrombocytopenia, XL, with/-out dyserythropoietic anemia (GATA1)
• Allelic: White blood cell count QTL (ACKR1)
• Allelic: Wiskott-Aldrich syndrome (WAS)
• Anauxetic dysplasia 1 (RMRP)
• Anemia, XL, with/-out neutropenia +/- platelet abnormalities (GATA1)
• Barth syndrome (TAFAZZIN)
• Benign ethnic neutropenia (ACKR1)
• Bone marrow failure syndrome 3 (DNAJC21)
• CINCA syndrome (NLRP3)
• Chediak-Higashi syndrome (LYST)
• Congenital disorder of glycosylation, type IIw (SLC37A4)
• Dursun syndrome (G6PC3)
• Familial Mediterranean fever, AD + AR (MEFV)
• Familial cold inflammatory syndrome 1 (NLRP3)
• Glycogen storage disease Ib + Ic (SLC37A4)
• Griscelli syndrome, type 1 (MYO5A)
• Griscelli syndrome, type 2 (RAB27A)
• Griscelli syndrome, type 3 (MLPH)
• Hyper-IgD syndrome (MVK)
• Keratoendothelitis fugax hereditaria (NLRP3)
• Marshall syndrome (COL11A1)
• Muckle-Wells syndrome (NLRP3)
• Myelokathexis, isolated (CXCR4)
• Neutropenia, cyclic (ELANE)
• Neutropenia, nonimmune chronic idiopathic, of adults (GFI1)
• Neutropenia, severe congenital 1, AD (ELANE)
• Neutropenia, severe congenital 2, AD (GFI1)
• Neutropenia, severe congenital 3, AR (HAX1)
• Neutropenia, severe congenital 4, AR (G6PC3)
• Neutropenia, severe congenital, 5, AR (VPS45)
• Neutropenia, severe congenital, 7, AR (CSF3R)
• Neutropenia, severe congenital, 8, AD (SRP54)
• Neutropenia, severe congenital, XL (WAS)
• Periodic fever, familial (TNFRSF1A)
• Reticular dysgenesis (AK2)
• Shwachman-Diamond syndrome (SBDS)
• Shwachman-Diamond syndrome 2 (EFL1)
• Transcobalamin II deficiency (TCN2)
• WHIM [Warts, Hypogammaglobulinemia, Infections, Myelokathexis] syndrome 1 (CXCR4)