Primary ficolin-3 deficiency D84.8

Mutations in the FCN3 gene located at chromosome 1p36.11. The proteins encoded by this gene, the ficolins are a group of proteins consisting of a collagen-like domain and a fibrinogen-like domain.

Ficolin-3 deficiency is caused by a mutation (+1637delC) in the FCN3 gene. It is a rare disorder that has been associated with both infections (in childhood) and autoimmune diseases such as systemic lupus erythematosus (SLE) (Troldborg A etal. 2019). One case with membranous glomerulonephritis and ficolin-3 deficiency was reported (Michalski M et al. 2015).

The pattern of transmission of complete FCN3 deficiency in the family reported by Schlapbach et al. (2011) was consistent with autosomal recessive inheritance. The parents who were heterozygous for the mutation showed an approximately 50% decrease in serum FCN3 levels, indicating haploinsufficiency.

Munthe-Fog et al (2009) reported a patient with immunodeficiency and recurrent infections since childhood who had complete ficolin-3 deficiency. Other features included brain abscesses and recurrent digital verrucae vulg.

Lab:Lymphocyte counts normal; T-cell responses normal; selectively deficient antibody response to pneumococcal polysaccharide vaccine.

Schlapbach et al (2011) reported two unrelated children who developed necrotizing enterocolitis associated with severe H-ficolin deficiency. One of the patients died at 4 weeks of age. The other patient recovered but had repeated skin infections with Staphylococcus aureus. At the age of 4 years, he had no more severe infections. Evidence was a homozygous truncating FCN3 polymorphism (604973.0001).

Michalski et al (2012) reported a male infant born at 35 weeks' gestation who developed Streptococcus agalactiae infection. Laboratory tests showed complete H-ficolin deficiency as well as low MBL (MBL2; 154545), undetectable MASP2 (605102), and low L-ficolin (FCN2; 601624). No severe infections occurred during the 5-year follow-up period, but microcephaly, poor growth, and mental retardation occurred. The patient was homozygous for the common truncating FCN3 polymorphism (604973.0001).

Michalski et al (2015) reported two unrelated patients with ficolin-3 deficiency. One was a 50-year-old man with nephrotic syndrome due to membranous glomerulonephritis. Immunosuppressive therapy resulted in reactivation of Epstein-Barr virus infection, which resolved after treatment was discontinued. He had no further serious infections during his lifetime. The other patient was an 11-month-old boy who had pneumonia before surgery to repair a ventricular septal defect. Both patients were homozygous for the common FCN3 polymorphism (604973.0001) and had decreased or undetectable serum ficolin-3 levels.

1. Michalski M et al. (2015) Primary ficolin-3 deficiency--is it associated with increased susceptibility to infections? (Letter) Immunobiology 220: 711-713.
2. Michalski M et al. (2012) H-ficolin (ficolin-3) concentrations and FCN3 gene polymorphism in neonates. Immunobiology 217: 730-737.
3. Munthe-Fog L et al (2009) Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency. New Eng J Med 360: 2637-2644.
4. Schlapbach LJ et al (2011) Congenital H-ficolin deficiency in premature infants with severe necrotising enterocolitis. (Letter) Gut 60: 1438-1439.
5. Troldborg A etal. (2019) Ficolin-3 Deficiency Is Associated with Disease and an Increased Risk of Systemic Lupus Erythematosus. J Clin Immunol 39:421-429.