A review from 2000 stated that life expectancy was reduced because of a tendency to develop cancer relatively early as well as deaths due to infections related to immunodeficiency.

There is no treatment for NBS, however in those with agammaglobulinemia, intravenous immunoglobulin may be started. Prophylactic antibiotics are considered to prevent urinary tract infections as those with NBS often have congenital kidney malformations. In the treat of malignancies radiation, alkylating antineoplastic agents, and epipodophyllotoxins are not used, and methotrexate can be used with caution and, the dose should be limited. Bone marrow transplants and hematopoietic stem cells transplants are also considered in the treatment of NBS. The supplementation of Vitamin E is also recommended. A ventriculoperitoneal shunt can be placed in patients with hydrocephaly, and surgical intervention of congenital deformities is also attempted.

Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date. Arts syndrome patients were also found to have reduced levels of hypoxanthine levels in urine and uric acid levels in the serum. In vitro, PRS-1 activity was reduced in erythrocytes and fibroblasts.

The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with telangiectasia and sometimes increased infections, and confirmed by specific laboratory abnormalities (elevated alpha-fetoprotein levels, increased chromosomal breakage or cell death of white blood cells after exposure to X-rays, absence of ATM protein in white blood cells, or mutations in each of the person’s ATM genes).

A variety of laboratory abnormalities occur in most people with A-T, allowing for a tentative diagnosis to be made in the presence of typical clinical features. Not all abnormalities are seen in all patients. These abnormalities include:

- Elevated and slowly increasing alpha-fetoprotein levels in serum after 2 years of age

- Immunodeficiency with low levels of immunoglobulins (especially IgA, IgG subclasses, and IgE) and low number of lymphocytes in the blood

- Chromosomal instability (broken pieces of chromosomes)

- Increased sensitivity of cells to x-ray exposure (cells die or develop even more breaks and other damage to chromosomes)

- Cerebellar atrophy on MRI scan

The diagnosis can be confirmed in the laboratory by finding an absence or deficiency of the ATM protein in cultured blood cells, an absence or deficiency of ATM function (kinase assay), or mutations in both copies of the cell’s ATM gene. These more specialized tests are not always needed, but are particularly helpful if a child’s symptoms are atypical.

All individuals with A-T should have at least one comprehensive immunologic evaluation that measures the number and type of lymphocytes in the blood (T-lymphocytes and B-lymphocytes), the levels of serum immunoglobulins (IgG, IgA, and IgM) and antibody responses to T-dependent (e.g., tetanus, Hemophilus influenzae b) and T-independent (23-valent pneumococcal polysaccharide) vaccines. For the most part, the pattern of immunodeficiency seen in an A-T patient early in life (by age five) will be the same pattern seen throughout the lifetime of that individual. Therefore, the tests need not be repeated unless that individual develops more problems with infection. Problems with immunity sometimes can be overcome by immunization. Vaccines against common bacterial respiratory pathogens such as Hemophilus influenzae, pneumococci and influenza virus (the “flu”) are commercially available and often help to boost antibody responses, even in individuals with low immunoglobulin levels. If the vaccines do not work and the patient continues to have problems with infections, gamma globulin therapy (IV or subcutaneous infusions of antibodies collected from normal individuals) may be of benefit. A small number of people with A-T develop an abnormality in which one or more types of immunoglobulin are increased far beyond the normal range. In a few cases, the immunoglobulin levels can be increased so much that the blood becomes thick and does not flow properly. Therapy for this problem must be tailored to the specific abnormality found and its severity.

If an individual patient’s susceptibility to infection increases, it is important to reassess immune function in case deterioration has occurred and a new therapy is indicated. If infections are occurring in the lung, it is also important to investigate the possibility of dysfunctional swallow with aspiration into the lungs (see above sections under Symptoms: Lung Disease and Symptoms: Feeding, Swallowing and Nutrition.)

Most people with A-T have low lymphocyte counts in the blood. This problem seems to be relatively stable with age, but a rare number of people do have progressively decreasing lymphocyte counts as they get older. In the general population, very low lymphocyte counts are associated with an increased risk for infection. Such individuals develop complications from live viral vaccines (measles, mumps, rubella and chickenpox), chronic or severe viral infections, yeast infections of the skin and vagina, and opportunistic infections (such as pneumocystis pneumonia). Although lymphocyte counts are often as low in people with A-T, they seldom have problems with opportunistic infections. (The one exception to that rule is that problems with chronic or recurrent warts are common.) The number and function of T-lymphocytes should be re-evaluated if a person with A-T is treated with corticosteroid drugs such as prednisone for longer than a few weeks or is treated with chemotherapy for cancer. If lymphocyte counts are low in people taking those types of drugs, the use of prophylactic antibiotics is recommended to prevent opportunistic infections.

If the tests show significant abnormalities of the immune system, a specialist in immunodeficiency or infectious diseases will be able to discuss various treatment options. Absence of immunoglobulin or antibody responses to vaccine can be treated with replacement gamma globulin infusions, or can be managed with prophylactic antibiotics and minimized exposure to infection. If antibody function is normal, all routine childhood immunizations including live viral vaccines (measles, mumps, rubella and varicella) should be given. In addition, several “special” vaccines (that is, licensed but not routine for otherwise healthy children and young adults) should be given to decrease the risk that an A-T patient will develop lung infections. The patient and all household members should receive the influenza (flu) vaccine every fall. People with A-T who are less than two years old should receive three (3) doses of a pneumococcal conjugate vaccine (Prevnar) given at two month intervals. People older than two years who have not previously been immunized with Prevnar should receive two (2) doses of Prevnar. At least 6 months after the last Prevnar has been given and after the child is at least two years old, the 23-valent pneumococcal vaccine should be administered. Immunization with the 23-valent pneumococcal vaccine should be repeated approximately every five years after the first dose.

In people with A-T who have low levels of IgA, further testing should be performed to determine whether the IgA level is low or completely absent. If absent, there is a slightly increased risk of a transfusion reaction. “Medical Alert” bracelets are not necessary, but the family and primary physician should be aware that if there is elective surgery requiring red cell transfusion, the cells should be washed to decrease the risk of an allergic reaction.

People with A-T also have an increased risk of developing autoimmune or chronic inflammatory diseases. This risk is probably a secondary effect of their immunodeficiency and not a direct effect of the lack of ATM protein. The most common examples of such disorders in A-T include immune thrombocytopenia (ITP), several forms of arthritis, and vitiligo.

Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.

The following chromosome instability syndromes are known:

- Ataxia telangiectasia

- Ataxia telangiectasia-like disorder

- Bloom syndrome

- Fanconi anaemia

- Nijmegen breakage syndrome

Revesz syndrome has so far been observed only in children. There is not much information about the disease because of its low frequency in general population and under reporting of cases.

Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides and open new avenues of therapeutic intervention. Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring.

Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.

This condition is rare. Only four cases have been described up to 2017.

The features of this condition include

- Facial dysmorphism

- Short stature

- Mild motor control and learning difficulties

- Mild ataxia

- Microcephaly

- Normal intelligence

- Conjunctival telangiectasia

- Recurrent sinus infections

- Decreased serum IgA

- Late onset of pulmonary fibrosis

- Increased alpha-fetoprotein

- Increased radiosensitivity

Diagnosis is suspected clinically and family history, neuroimaging and genetic study helps to confirm Behr Syndrome.

Blood lactate and pyruvate levels usually are elevated as a result of increased anaerobic metabolism and a decreased ratio of ATP:ADP. CSF analysis shows an elevated protein level, usually >100 mg/dl, as well as an elevated lactate level.

A neuro-ophthalmologist is usually involved in the diagnosis and management of KSS. An individual should be suspected of having KSS based upon clinical exam findings. Suspicion for myopathies should be increased in patients whose ophthalmoplegia does not match a particular set of cranial nerve palsies (oculomotor nerve palsy, fourth nerve palsy, sixth nerve palsy). Initially, imaging studies are often performed to rule out more common pathologies. Diagnosis may be confirmed with muscle biopsy, and may be supplemented with PCR determination of mtDNA mutations.

Diffuse, symmetric white matter abnormalities were demonstrated by magnetic resonance imaging (MRI) suggesting that Behr syndrome may represent a disorder of white matter associated with an unknown biochemical abnormality.

LIG4 syndrome (also known as Ligase IV syndrome) is an extremely rare condition caused by mutations in the DNA Ligase IV (LIG4) gene. Some mutations in this gene are associated with a resistance against multiple myeloma and Severe Combined Immunodeficiency. Severity of symptoms depends on the degree of reduced enzymatic activity of Ligase IV or gene expression.

As DNA ligase IV is essential in V(D)J recombination, the mechanism by which immunoglobulins, B cell and T cell receptors are formed, patients with LIG4 syndrome may suffer from less effective or defective V(D)J recombination. Some patients have a severe immunodeficiency characterized by pancytopenia, causing chronic respiratory infections and sinusitis. Clinical features also include Seckel syndrome-like facial abnormalities and microcephaly. Patients also suffer from growth retardation and skin conditions, including photosensitivity, psoriasis and telangiectasia. Although not present in all, patients may also present with hypothyroidism and type II diabetes and possibly malignancies such as acute T-cell leukemia. The clinical phenotype of LIG4 syndrome closely resembles that of Nijmegen breakage syndrome (NBS).

No treatment is available for most of these disorders. Mannose supplementation relieves the symptoms in PMI-CDG (CDG-Ib) for the most part, even though the hepatic fibrosis may persist. Fucose supplementation has had a partial effect on some SLC35C1-CDG (CDG-IIc or LAD-II) patients.

Different types of ataxia:

- congenital ataxias (developmental disorders)

- ataxias with metabolic disorders

- ataxias with a DNA repair defect

- degenerative ataxias

- ataxia associated with other features.

Revesz syndrome is a genetic disease thought to be caused by short telomeres. Patients with Revesz syndrome have presented with heterozygous mutations in TINF2 gene which is located on chromosome 14q12. There is no treatment for this disease yet.

The Seckel syndrome or microcephalic primordial dwarfism (also known as bird-headed dwarfism, Harper's syndrome, Virchow-Seckel dwarfism, and Bird-headed dwarf of Seckel) is an extremely rare congenital nanosomic disorder.

Inheritance is autosomal recessive.

It is characterized by intrauterine growth retardation and postnatal dwarfism with a small head, narrow bird-like face with a beak-like nose, large eyes with down-slanting palpebral fissures , receding mandible and intellectual disability.

A mouse model has been developed. This mouse model is characterized by a severe deficiency of ATR protein. These mice suffer high levels of replicative stress and DNA damage. Adult Seckel mice display accelerated aging. These findings are consistent with the DNA damage theory of aging.

In most cases, between the age of 2 and 4 oculomotor signals are present. Between the age of 2 and 8, telangiectasias appears. Usually by the age of 10 the child needs a wheel chair. Individuals with autosomal recessive cerebellum ataxia usually survive till their 20s; in some cases individuals have survived till their 40s or 50s.

It is supposed to be caused by defects of genes on chromosome 3 and 18. One form of Seckel syndrome can be caused by mutation in the gene encoding the ataxia telangiectasia and Rad3 related protein () which maps to chromosome 3q22.1-q24. This gene is central in the cell's DNA damage response and repair mechanism.

Types include:

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.

While the clinical picture may point towards the diagnosis of the Roussy–Lévy syndrome, the condition can only be confirmed with absolute certainty by carrying out genetic testing in order to identify the underlying mutations.

Diagnosis is visual with measurement of spot size. The number of spots can have clinical significance for diagnosis of associated disorders such as Neurofibromatosis type I. Greater than or equal to 6 spots of at least 5mm in diameter in pre-pubertal children and at least 15mm in post-pubertal individuals is one of the major diagnostic criteria for NF1.

Café au lait spots can be removed with lasers. Results are variable as the spots are often not completely removed or can come back after treatment. Often, a test spot is treated first to help predict the likelihood of treatment success.