The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are autosomal recessive, while properdin deficiency could be X-linked inheritance, and finally MBL deficiency can be both.

Acquired hypocomplementemia may occur in the setting of bone infections (osteomyelitis), infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low C3 and C4 Membranoproliferative glomerulonephritis usually has low C3.

Patients with terminal complement pathway deficiency should receive meningococcal and pneumococcal vaccinations. They can receive live vaccines.

By definition, primary immune deficiencies are due to genetic causes. They may result from a single genetic defect, but most are multifactorial. They may be caused by recessive or dominant inheritance. Some are latent, and require a certain environmental trigger to become manifest, like the presence in the environment of a reactive allergen. Other problems become apparent due to aging of bodily and cellular maintenance processes.

A survey of 10,000 American households revealed that the prevalence of diagnosed primary immunodeficiency approaches 1 in 1200. This figure does not take into account people with mild immune system defects who have not received a formal diagnosis.

Milder forms of primary immunodeficiency, such as selective immunoglobulin A deficiency, are fairly common, with random groups of people (such as otherwise healthy blood donors) having a rate of 1:600. Other disorders are distinctly more uncommon, with incidences between 1:100,000 and 1:2,000,000 being reported.

Suspect terminal complement pathway deficiency with patients who have more than one episode of Neisseria infection.

Initial complement tests often include C3 and C4, but not C5 through C9. Instead, the CH50 result may play a role in diagnosis: if the CH50 level is low but C3 and C4 are normal, then analysis of the individual terminal components may be warranted.

Complement 2 deficiency is a type of complement deficiency caused by any one of several different alterations in the structure of complement component 2.

It has been associated with an increase in infections.

It can present similarly to systemic lupus erythematosus (SLE).

Complement 4 deficiency is a genetic condition affecting complement component 4.

It can present with lupus-like symptoms.

Complement 3 deficiency is a genetic condition affecting complement component 3.

It can cause systemic lupus erythematosus-like symptoms.

It can lead to an increase in pyogenic infections from encapsulated bacteria.

Properdin deficiency is a rare X-linked disease in which properdin, an important complement factor, is deficient. Affected individuals are susceptible to fulminant meningococcal disease.

Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes (APSs), polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes, are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected.There are three types of APS or (in terms that mean the same thing) three APSs, and there are a number of other diseases which have endocrine autoimmunity.

Symptoms can be reduced through avoidance of leucine, an amino acid. Leucine is a component of most protein-rich foods; therefore, a low-protein diet is recommended. Some isolated cases of this disorder have responded to supplemental biotin; this is not altogether surprising, consider that other biotin-related genetic disorders (such as biotinidase deficiency and holocarboxylase synthetase deficiency) can be treated solely with biotin. Individuals with these multiple carboxylase disorders have the same problem with leucine catabolism as those with 3-methylcrotonyl-CoA carboxylase deficiency.

It is one of the 29 conditions currently recommended for newborn screening by the American College of Medical Genetics.

Estimating the mortality rate based on the available literature is difficult. Several case reports have revealed an association between acquired partial lipodystrophy and other diseases.

Nephropathy, in the form of membranoproliferative glomerulonephritis, occurs in about 20% of patients. Usually, patients do not have clinically evident renal disease or abnormalities in renal function until they have had the disease for 8 or more years. Membranoproliferative glomerulonephritis usually presents with asymptomatic proteinuria or hematuria.

The disease may gradually progress. About 40-50% of patients develop end-stage renal disease over the course of 10 years. This condition is responsible for most recurrent hospital admissions in patients with acquired partial lipodystrophy. Rapid progression of renal disease in a pregnant patient was reported. Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations.

Associated autoimmune diseases (e.g., systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population. Although uncommon, insulin resistance increases cardiovascular risk. Susceptibility to bacterial infections probably results from a C3 deficiency (due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial killing.

Around 250 cases have been reported since the recognition of this syndrome. It is a rare syndrome with no known prevalence, although it is more common than the generalized form of acquired lipodystrophy (Lawrence syndrome).

- Race: No clear relationship exists between incidence and race in this syndrome; however, most reported patients have been of European descent.

- Age: The median age of onset of lipodystrophy has been reported to be around seven years; however, onset occurring as late as the fourth or fifth decade of life also has been reported. The median age at presentation has been about 25 years, and women have been found to present later than men (age 28 for women, age 18 for men).

- Sex: Analysis of the pooled data revealed female patients were affected about four times more often than males.

Leukocyte adhesion deficiency-1 (LAD1) is a rare and often fatal genetic disorder in humans.

Each "type" of this condition has a different cause, in terms of IPEX syndrome is inherited in males by an x-linked recessive process. FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of the IPEX condition.

Because the CD18 gene has been cloned and sequenced, this disorder is a potential candidate for gene therapy.

The cause of GS has not been discovered. The basic defect is most likely in the bone marrow and there is some evidence of autoimmune pathogenesis.

The mainstay of treatment consists of thymectomy and immunoglobulin replacement with IVIG (Kelesidis, 2010). Immunodeficiency does not resolve after thymectomy (Arnold, 2015). To treat the autoimmune component of the disease, immune-suppression is sometimes used and it is often challenging to determine if a patient’s symptoms are infectious or autoimmune (Arnold, 2015).

Patients should have serological testing for antibodies to toxoplasma and cytomegalovirus. If receiving a transfusion, CMV negative blood should be used in those with negative serological testing. Live vaccines should also be avoided (Kelesidis, 2010). The CDC recommends pneumococcal, meningococcal, and Hib vaccination in those with diminished humoral and cell-mediated immunity (Hamborsky, 2015).

Some have advocated treating prophylactically with TMP-SMX if CD4 counts are lower than 200 cells/mm^3, similar to AIDS patients (Kelesidis, 2010).

Primary immune deficiency diseases are those caused by inherited genetic mutations. Secondary or acquired immune deficiencies are caused by something outside the body such as a virus or immune suppressing drugs.

Primary immune diseases are at risk to an increased susceptibility to, and often recurrent ear infections, pneumonia, bronchitis, sinusitis or skin infections. Immunodeficient patients may less frequently develop abscesses of their internal organs, autoimmune or rheumatologic and gastrointestinal problems.

- Primary immune deficiencies

- Severe combined immunodeficiency (SCID)

- DiGeorge syndrome

- Hyperimmunoglobulin E syndrome (also known as Job’s Syndrome)

- Common variable immunodeficiency (CVID): B-cell levels are normal in circulation but with decreased production of IgG throughout the years, so it is the only primary immune disorder that presents onset in the late teens years.

- Chronic granulomatous disease (CGD): a deficiency in NADPH oxidase enzyme, which causes failure to generate oxygen radicals. Classical recurrent infection from catalase positive bacteria and fungi.

- Wiskott-Aldrich syndrome (WAS)

- Autoimmune lymphoproliferative syndrome (ALPS)

- Hyper IgM syndrome: X-linked disorder that causes a deficiency in the production of CD40 ligand on activated T-cells. This increases the production and release of IgM into circulation. The B-cell and T-cell numbers are within normal limits. Increased susceptibility to extracellular bacteria and opportunistic infections.

- Leukocyte adhesion deficiency (LAD)

- NF-κB Essential Modifier (NEMO) Mutations

- Selective immunoglobulin A deficiency: the most common defect of the humoral immunity, characterized by a deficiency of IgA. Produces repeating sino-pulmonary and gastrointestinal infections.

- X-linked agammaglobulinemia (XLA; also known as Bruton type agammaglobulinemia): characterized by a deficiency in tyrosine kinase enzyme that blocks B-cell maturation in the bone marrow. No B-cells are produced to circulation and thus, there are no immunoglobulin classes, although there tends to be a normal cell-mediated immunity.

- X-linked lymphoproliferative disease (XLP)

- Ataxia-telangiectasia

- Secondary immune deficiencies

- AIDS

Zinc deficiency in children can cause delayed growth and has been claimed to be the cause of stunted growth in one third of the world's population.

An allergy is an abnormal immune reaction to a harmless antigen.

- Seasonal allergy

- Mastocytosis

- Perennial allergy

- Anaphylaxis

- Food allergy

- Allergic rhinitis

- Atopic dermatitis

Zinc deficiency during pregnancy can negatively affect both the mother and fetus. Animal studies indicate that maternal zinc deficiency can upset both the sequencing and efficiency of the birth process. An increased incidence of difficult and prolonged labor, hemorrhage, uterine dystocia and placental abruption has been documented in zinc deficient animals. These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger protein. A review of pregnancy outcomes in women with acrodermatitis enteropathica, reported that out of every seven pregnancies, there was one abortion and two malfunctions, suggesting the human fetus is also susceptible to the teratogenic effects of severe zinc deficiency. However, a review on zinc supplementation trials during pregnancy did not report a significant effect of zinc supplementation on neonatal survival.

Zinc deficiency can interfere with many metabolic processes when it occurs during infancy and childhood, a time of rapid growth and development when nutritional needs are high. Low maternal zinc status has been associated with less attention during the neonatal period and worse motor functioning. In some studies, supplementation has been associated with motor development in very low birth weight infants and more vigorous and functional activity in infants and toddlers.

Protein S deficiency is a disorder associated with increased risk of venous thrombosis. Protein S, a vitamin K-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activate protein C in the degradation of factor Va and factor VIIIa. Decreased (antigen) levels or impaired function of protein S leads to decreased degradation of factor Va and factor VIIIa and an increased propensity to venous thrombosis. Protein S circulates in human plasma in two forms: approximately 60 percent is bound to complement component C4b β-chain while the remaining 40 percent is free, only free protein S has activated protein C cofactor activity