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Mannose-binding lectin deficiency

Authors
Maarten W Bronkhorst, MD, FEBS, FRCS
Lee H Bouwman, MD, PhD, FEBVS
Section Editor
Luigi D Notarangelo, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Mannose-binding lectin (MBL), also known as mannan-binding protein (MBP), is a protein that is involved in complement activation via the lectin pathway (figure 1). The complement system provides immediate defense against infection and has proinflammatory effects.

MBL deficiency has been variously defined as a serum levels either <100 or <500 ng/mL. It is a laboratory finding that does not necessarily equate to a clinical disorder. Numerous case-control studies with widely varying methodologies have reported that MBL deficiency is associated with a large and heterogeneous group of disease processes. However, subnormal levels are also found in healthy people. To date, there is no consensus on the clinical relevance of MBL deficiency or its treatment.

This topic reviews the genetics, epidemiology, diagnosis, and management of MBL deficiency and also reviews diseases associated with both low and high levels of MBL. Genetic defects and polymorphisms of the MBL2 gene, the function of the MBL protein, and other disorders of the complement system are discussed separately. (See "Mannose-binding lectin" and "Inherited disorders of the complement system" and "Acquired deficiencies of the complement system".)

EPIDEMIOLOGY

Genetic variants within the mannose-binding lectin 2 (MBL2) gene are extremely common [1,2]. Heterozygosity, or the presence of a DNA variant in one MBL2 allele, is found in more than 30 percent of the population in most ethnic groups evaluated. Thus, up to 40 percent of most populations may have single nucleotide polymorphisms (SNPs) in one or both MBL2 alleles [3,4]. (See "Mannose-binding lectin", section on 'The MBL gene'.)

PATHOPHYSIOLOGY

Genetics — The normal or wild-type MBL2 allele is referred to as "A." Three structural region point mutations have been identified, all in exon 1, designated alleles "B," "C," and "D." As a group, these variant alleles have also been referred to as "O." There is an autosomal pattern of inheritance. However, the MBL serum phenotype is gene-dose dependent, so inheritance cannot be defined as dominant or recessive. The level of functional MBL is decreased by as much as 90 percent, even in heterozygotes. The effect of the D allele in heterozygotes is less dramatic than that of the B or C alleles. (See "Mannose-binding lectin", section on 'The MBL gene'.)

                     

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Literature review current through: Nov 2016. | This topic last updated: Mon Jun 13 00:00:00 GMT 2016.
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