hypoproteinemia, hypercatabolic

Hypoproteinemia, hypercatabolic (also called Beta-2-microglobulin deficiency or immunodeficiency 43) is an inherited disorder that primarily affects the immune and respiratory systems. It results from pathogenic variants in the B2M gene, which encodes beta-2-microglobulin, a protein required for normal immune surveillance. Lack of functional beta-2-microglobulin leads to low blood protein levels and a heightened breakdown of serum proteins, leaving individuals vulnerable to severe, recurrent lung infections. Symptoms usually become apparent in childhood, although the exact age of onset can vary. Fewer than several dozen families have been reported, so precise prevalence estimates are not well established.

Bronchiectasis and persistent hypoproteinemia are defining features and are present in every reported individual. Many children first come to medical attention with repeated respiratory infections that progress to chronic airway damage, visible on chest imaging as bronchiectasis or organizing pneumonia. Laboratory testing consistently shows very low serum beta-2-microglobulin, reduced albumin, and markedly decreased immunoglobulin G (IgG), along with a poor antibody response to polysaccharide vaccines. Over time, some individuals develop lung abscesses or subcutaneous nodules, and immune cell studies may reveal reduced natural killer cells or low total B-cell counts. Not all individuals experience all features, and severity varies considerably.

The condition is caused by autosomal recessive variants in the B2M gene. Beta-2-microglobulin forms part of the major histocompatibility complex class I molecule, which presents protein fragments to immune cells. Without this component, immune signaling is impaired and serum proteins are broken down more rapidly, leading to the characteristic hypoproteinemia and susceptibility to infection. Because the disorder is autosomal recessive, a child must inherit one altered copy of B2M from each carrier parent to be affected. Carrier parents are typically healthy but have a 25 percent chance with each pregnancy to have an affected child and a 50 percent chance to have a carrier child. Extended family members may wish to pursue carrier testing and genetic counseling.

Currently, management focuses on supportive care tailored to each individual’s needs. Aggressive treatment of respiratory infections, routine pulmonary hygiene, and regular monitoring by immunology and pulmonology specialists form the backbone of care. Nutritional support may be required to address ongoing protein loss. Because this is an inherited condition, affected families benefit from genetic counseling to discuss recurrence risks and testing options for relatives. Patients should discuss treatment strategies with their healthcare team to determine the most appropriate interventions for their situation.

Long-term outlook depends on the severity of lung disease and the effectiveness of infection control. With vigilant respiratory care and prompt treatment of infections, many individuals achieve improved quality of life, although chronic lung damage can progress and may require ongoing intervention. Outcomes vary widely, reflecting differences in infection burden, access to multidisciplinary care, and individual response to therapy.