Masp2 Deficiency

MASP2 deficiency is caused by an autosomal recessive homozygous mutation in the MASP2 gene (605102) located at chromosome 1p36.

MASP2 deficiency is defined as MASP2 protein levels < 100 ng/ml, occurs in about 4% of Caucasians and in up to 18% of some African populations. Some individuals with MASP2 deficiency are at increased risk for infection or autoimmune disease, but most are asymptomatic. MASP2 plays a role in activating the lectin pathway of the complement system; therefore, deficiency can lead to defects in the complement system (Thiel et al. 2007; Sokolowska et al. 2015).

Stengaard-Pedersen et al (2003) described a patient with an inherited deficiency of MASP2 who was healthy until the age of 13 years when a diagnosis of ulcerative colitis was made. At the age of 29 years: erythema multiforme.

Systemic lupus erythematosus was suspected based on joint symptoms and myalgias combined with a weakly positive antinuclear antibody test. The patient responded well to treatment with prednisolone, and additional immunosuppressive medications were subsequently started. Subsequently, severe pneumococcal pneumonia with sepsis was documented several times. Progressive pulmonary fibrosis was diagnosed at the age of 30 years. Lab: MASP2 protein level was < 10 ng/ml, indicating severe deficiency. The patient's MBL-MASP complex contained MASP1 and the MASP1 isoform MASP3, but not MASP2 or the MASP2 isoform MAP19.

Sokolowska et al (2015) reported 2 unrelated individuals with pulmonary tuberculosis who were homozygous for the MASP2 D120G polymorphism. All 3 individuals had low serum MASP2 concentrations and low MBL-MASP2 complex activities. One of the tuberculosis patients also had an MBL2 (154545) mutation (154545.0001) that affected both MBL serum concentration and activity. Sokolowska et al (2015), in a review of published cases, including both of their cases, noted that 10 patients were reported with MASP2 deficiency and severe disease, mainly affecting the respiratory tract. However, they also found homozygous deficiency for MASP2 in 7 healthy controls.

St. Swierzko et al (2009) studied MASP2 concentrations in cord blood in a large cohort of 1 788 newborns of Caucasian origin: the median value was 93 ng/ml. Newborns with MASP2 concentrations less than 42 ng/ml were considered MASP2-deficient and had a shorter mean gestational age and a higher incidence of preterm birth and low birth weight. There was no association between this SNP and preterm birth, low birth weight, or perinatal infections.

1. Sokolowska A et al. (2015) Mannan-binding lectin-associated serine protease-2 (MASP-2) deficiency in two patients with pulmonary tuberculosis and one healthy control. Cell Molec Immun 12: 119-121.
2. St. Swierzko A et al. (2009) Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large cohort of neonates and its clinical associations. Molec. Immun. 46: 1696-1701.
3. Stengaard-Pedersen K et al (2003) Inherited deficiency of mannan-binding lectin-associated serine protease 2. New Eng J Med 349: 554-560.
4. Thiel S et al (2007) Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun 8: 154-163.