Among the diagnostic tests that can be done in determining if an individual has complement deficiencies is:

- CH50 measurement

- Immunochemical methods/test

- C3 deficiency screening

- Mannose-binding lectin (lab study)

- Plasma levels/regulatory proteins (lab study)

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

In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).

Pneumococcus and haemophilus infections prevention can be taken via immunization for those with complement deficiency. Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.

The basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte and granulocyte counts) and immunoglobulin levels (the three most important types of antibodies: IgG, IgA and IgM).

Other tests are performed depending on the suspected disorder:

- Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocytes): different groups of T lymphocytes (dependent on their cell surface markers, e.g. CD4+, CD8+, CD3+, TCRαβ and TCRγδ), groups of B lymphocytes (CD19, CD20, CD21 and Immunoglobulin), natural killer cells and monocytes (CD15+), as well as activation markers (HLA-DR, CD25, CD80 (B cells).

- Tests for T cell function: skin tests for delayed-type hypersensitivity, cell responses to mitogens and allogeneic cells, cytokine production by cells

- Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses

- Tests for phagocyte function: reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity.

Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.

Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease are present, but not all.

Those affected with deficiency of the interleukin-1–receptor antagonist can have diagnosis achieved via noting an increase of erythrocyte sedimentation rate, as well as the following:

- Genetic test

- Radiological findings

- Clinical findings

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.

Flow cytometry with monoclonal antibodies is used to screen for deficiencies of CD18.

In terms of treatment a 2013 review indicates that colchicine can be used for DIRA. Additionally there are several other management options such as anakinra, which blocks naturally occurring IL-1, this according to a 2016 pediatric textbook.

The diagnosis of the disease is mainly clinical (see diagnostic criteria). A laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).

- Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.

- Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein cholesterol levels.

- Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.

- Antinuclear antibodies (ANA) and antidouble-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.

- A genetic workup should be performed if the familial form of lipodystrophy is suggested.

Laboratory work for associated diseases includes:

- Metabolic disease - fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome.

- Autoimmune disease - ANA, antidouble-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF.

As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.

Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.

In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.

In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.

A review published in 2004, which was based on 35 patients seen by the respective authors over 8 years and also a literature review of 220 cases of acquired partial lipodystrophy (APL), proposed an essential diagnostic criterion. Based on the review and the authors experience, they proposed that APL presents as a gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the "cephalocaudal" sequence, sparing the lower extremities. The median age of the onset of lipodystrophy was seven years. Several autoimmune diseases, in particular systemic lupus erythematosus and dermatomyositis, were associated with APL. The prevalence rates of diabetes mellitus and impaired glucose tolerance were 6.7% and 8.9%, respectively. Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. About 22% of patients developed membranoproliferative glomerulonephritis (MPGN) after a median of about 8 years following the onset of lipodystrophy. Compared with patients without renal disease, those with MPGN had earlier age of onset of lipodystrophy (12.6 ± 10.3 yr vs 7.7 ± 4.4 yr, respectively; p < 0.001) and a higher prevalence of C3 hypocomplementemia (78% vs 95%, respectively; p = 0.02).

The adipose stores of the gluteal regions and lower extremities (including soles) tend to be either preserved or increased, particularly among women. Variable fat loss of the palms, but no loss of intramarrow or retro-orbital fat, has been demonstrated.

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

There is no treatment for MKD. But, the inflammation and the other effects can be reduced to a certain extent.

- IL-1 targeting drugs can be used to reduce the effects of the disorder. Anakinra is antagonist to IL-1 receptors. Anakinra binds the IL-1 receptor, preventing the actions of both IL-1α and IL-1β, and it has been proved to reduce the clinical and biochemical inflammation in MKD. It can effectively decreases the frequency as well as the severity of inflammatory attacks when used on a daily basis. Disadvantages with the usage of this drug are occurrence of painful injection site reaction and as the drug is discontinued in the near future the febrile attacks start. (Examined in a 12-year-old patient).

- Canakinumab is a long acting monoclonal antibody which is directed against IL-1β has shown to be effective in reducing both frequency and severity in patients suffering from mild and severe MKD in case reports and observational case series. It reduces the physiological effects but the biochemical parameter still remain elevated (Galeotti et al. demonstrated that it is more effective than anakinra –considered 6 patients suffering from MKD).

- Anti-TNF therapy might be effective in MKD, but the effect is mostly partial and therapy failure and clinical deterioration have been described frequently in patients on infliximab or etanercept. A beneficial effect of human monoclonal anti-TNFα antibody adalimumab was seen in a small number of MKD patients.

- Most MKD patients are benefited by anti-IL-1 therapy. However, anti-IL-1-resistant disease may also occur. Example. tocilizumab (a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor). This drug is used when the patients are unresponsive towards Anakinra. (Shendi et al. treated a young woman in whom anakinra was ineffective with tocilizumab). It was found that it was effective in reducing the biochemical and clinical inflammation [30].Stoffels et al. observed reduction of frequency and severity of the inflammatory attacks, although after several months of treatment one of these two patients persistently showed mild inflammatory symptoms in the absence of biochemical inflammatory markers.

- A beneficial effect of hematopoietic stem cell transplantation can be used in severe mevalonate kinase deficiency conditions (Improvement of cerebral myelinisation on MRI after allogenic stem cell transplantation was observed in one girl). But, liver transplantation did not influence febrile attacks in this patient.

CD25 deficiency or interleukin 2 receptor alpha deficiency is an immunodeficiency disorder associated with mutations in the interleukin 2 receptor alpha (CD25) (IL2RA) gene. The mutations cause expression of a defective α chain or complete absence thereof, an essential part of high-affinity interleukin-2 (IL-2) receptors. The result is a syndrome described as IPEX-like or a SCID.

In one patient, deficiency of CD25 on CD4+ lymphocytes caused significantly impaired sensitivity to IL-2. This was demonstrated by a lack of measurable response in anti-inflammatory interleukin-10 (IL-10) secretion to low-dose IL-2 incubation. Greatly reduced IL-10 secretion compared to healthy humans results in a syndrome comparable to IPEX syndrome, a type of autoimmunity which is caused by FoxP3 transcription factor dysfunction. In addition to IPEX-like symptoms, CD25 deficiency increases susceptibility to viral infections and possibly fungal and bacterial infections.

As IL-2 is an important inducer of lymphocyte proliferation, the absence of highly sensitive IL-2 receptors may also significantly hinder activation and clonal expansion of CD8+ and CD4+ lymphocytes and NK cells. One case also reported the absence of CD1, a MHC-like glycoprotein involved in the presentation of lipid antigens to T cells, in a CD25 deficient patient. Furthermore, chronic upregulation of anti-apoptotic Bcl-2 in thymocytes was also described possibly allowing autoreactive T cells to escape deletion.

HFM must be distinguished from cerebral folate deficiency (CFD)– a condition in which there is normal intestinal folate absorption, without systemic folate deficiency, but a decrease in CSF folate levels. This can accompany a variety of disorders. One form of CFD is due to loss-of-mutations in folate receptor-α, (FRα), which transports folates via an endocytic process. While PCFT is expressed primarily at the basolateral membrane of the choroid plexus, FRα, is expressed primarily at the apical brush-border membrane. Unlike subjects with HFM, patients with CFD present with neurological signs a few years after birth. The basis for the delay in the appearance of clinical manifestations due to loss of FRα function is not clear; the normal blood folate levels may be protective, although for a limited time.

The CSF folate level is usually undetectable at the time of diagnosis. Even when the blood folate level is corrected, or far above normal, the CSF folate level remains low, consistent with impaired transport across the choroid plexus. The normal CSF folate level in children over the first three years of life is in the 75 to 150 nM range. In subjects with HFM it is very difficult indeed, rarely possible, to bring the CSF folate level into the normal range even with substantial doses of parenteral folate (see below).

Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the enzyme mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36).

The disorder was first described in 1985.

Classified as an inborn error of metabolism, mevalonate kinase deficiency usually results in developmental delay, hypotonia, anemia, hepatosplenomegaly, various dysmorphic features, mental retardation, an overall failure to thrive and several other features.

There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders; however, some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus, or ciclosporin.

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.

No cure currently exists; however, gene therapy has been proposed.

Detection of the disorder is possible with an organic acid analysis of the urine. Patients with SSADH deficiency will excrete high levels of GHB but this can be difficult to measure since GHB has high volatility and may be obscured on gas chromatography or mass spectrometry studies by a high urea peak. Other GABA metabolites can also be identified in urine such as glycine. Finally, succinic semialdehyde dehydrogenase levels can be measured in cultured leukocytes of the patient. This occurs due to the accumulation of 4,5-dihydroxyhexanoic acid which is normally undetectable in mammalian tissues but is characteristic of SSADH deficiency. This agent can eventually compromise the pathways of fatty acid, glycine, and pyruvate metabolism, and then become detectable in patients' leukocytes. Such enzyme levels can also be compared to non-affected parents and siblings.

Viral infection is a very common cause of lymphoproliferative disorders. In children, the most common is believed to be congenital HIV infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.

Since the essential pathology is due to the inability to absorb vitamin B from the bowels, the solution is therefore injection of IV vitamin B. Timing is essential, as some of the side effects of vitamin B deficiency are reversible (such as RBC indices, peripheral RBC smear findings such as hypersegmented neutrophils, or even high levels of methylmalonyl CoA), but some side effects are irreversible as they are of a neurological source (such as tabes dorsalis, and peripheral neuropathy). High suspicion should be exercised when a neonate, or a pediatric patient presents with anemia, proteinuria, sufficient vitamin B dietary intake, and no signs of pernicious anemia.

Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.