The diagnosis is made on the basis of clinical parameters, the peripheral blood smear, and low immunoglobulin levels. Typically, IgM levels are low, IgA levels are elevated, and IgE levels may be elevated; paraproteins are occasionally observed. Skin immunologic testing (allergy testing) may reveal hyposensitivity. Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on the basis of low platelets and infections, and bone marrow biopsy may be performed. Decreased levels of Wiskott-Aldrich syndrome protein and/or confirmation of a causative mutation provides the most definitive diagnosis.

Sequence analysis can detect the WAS-related disorders of Wiskott–Aldrich syndrome, XLT, and XLN. Sequence analysis of the "WASp" gene can detect about 98% of mutations in males and 97% of mutations in female carriers. Because XLT and XLN symptoms may be less severe than full WAS and because female carriers are usually asymptomatic, clinical diagnosis can be elusive. In these cases, genetic testing can be instrumental in diagnosis of WAS-related disorders.

Jin et al. (2004) employ a numerical grading of severity:

- 0.5: intermittent thrombocytopenia

- 1.0: thrombocytopenia and small platelets (microthrombocytopenia)

- 2.0: microthrombocytopenia plus normally responsive eczema or occasional upper respiratory tract infections

- 2.5: microthrombocytopenia plus therapy-responsive but severe eczema or airway infections requiring antibiotics

- 3.0: microthrombocytopenia plus both eczema and airway infections requiring antibiotics

- 4.0: microthrombocytopenia plus eczema continuously requiring therapy and/or severe or life-threatening infections

- 5.0: microthrombocytopenia plus autoimmune disease or malignancy

The diagnosis of immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is consistent with the following criteria:

- Clinical examination

- Family history

- Laboratory findings

- Genetic testing

A prenatal diagnostic is possible and very reliable when mother is carrier of the syndrome. First, it's necessary to determine the fetus' sex and then study X-chromosomes. In both cases, the probability to transfer the X-chromosome affected to the descendants is 50%. Male descendants who inherit the affected chromosome will express the symptoms of the syndrome, but females who do will be carriers.

XLI can be suspected based on clinical findings, although symptoms can take varying amounts of time to become evident, from a few hours after birth, up to a year in milder cases. The diagnosis is usually made by a dermatologist, who also typically formulates the treatment plan (see below). STS enzyme deficiency is confirmed using a clinically available biochemical assay. Carrier detection can be performed in mothers of affected sons using this test (see Genetics, below). Molecular testing for DNA deletions or mutations is also offered, and can be particularly useful in the evaluation of individuals with associated medical conditions (see below). Prenatal diagnosis is possible using either biochemical or molecular tests. However, the use of prenatal diagnosis for genetic conditions that are considered to be generally benign raises serious ethical considerations and requires detailed genetic counseling.

Due to the wide range of genetic disorders that are presently known, diagnosis of a genetic disorder is widely varied and dependent of the disorder. Most genetic disorders are diagnosed at birth or during early childhood, however some, such as Huntington's disease, can escape detection until the patient is well into adulthood.

The basic aspects of a genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination. Prenatal diagnosis can detect the presence of characteristic abnormalities in fetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.

Menkes syndrome can be diagnosed by blood tests of the copper and ceruloplasmin levels, skin biopsy, and optical microscopic examination of the hair to view characteristic Menkes abnormalities. X-rays of the skull and skeleton are conducted to look for abnormalities in bone formation. Urine homovanillic acid/vanillylmandelic acid ratio has been proposed as a screening tool to support earlier detection. Since 70% of MNK cases are inherited, genetic testing of the mother can be performed to search for a mutation in the ATP7A gene.

X-ray and neuroimaging studies may be helpful in confirming a diagnosis of Coffin–Lowry syndrome. Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin–Lowry syndrome. Studies of enzyme activity can not be used to diagnose an affected female.

Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RSK2 gene. This testing can be used to confirm but not rule out the diagnosis of Coffin–Lowry syndrome because not all affected individuals have a detectable mutation.

The diagnosis of hyper IgM syndrome can be done via the following methods and tests:

- MRI

- Chest radiography

- Pulmonary function test

- Lymph node test

- Laboratory test (to measure CD40)

A diagnosis can be made on the combination of clinical features. This can then be confirmed by gene sequencing.

Aside from observing the symptoms characteristic of X-linked thrombocytopenia in infancy (easy bruising, mild anemia, mucosal bleeding), molecular genetic testing would be done to confirm the diagnosis. Furthermore, flow cytometry or western blotting would be used to test for decreased or absent amounts of WASp. Family history would also assist in diagnosis, with specific attention to maternally related males with "WAS"-related disorders. Because "WAS"-related disorders are phenotypically similar, it is important to confirm the absence of the diagnostic criteria for Wiskoff-Aldrich syndrome at the outset. These diagnostic criteria include eczema, lymphoma, autoimmune disorder, recurrent bacterial or viral infections, family history of maternally related males with a "WAS"-related disorder, and absent or decreased "WASp". X-linked congenital neutropenia can be diagnostically distinguished from XLT with persistent neutropenia, arrested development of the bone marrow, and normal "WASp" expression.

CDPX1 activity may be inhibited by warfarin because it is believed that ARSE has enzymatic activity in a vitamin K producing biochemical pathway. Vitamin K is also needed for controlling binding of calcium to bone and other tissues within the body.

Patients presenting with this disease undergo antibiotic treatment and gammaglobulin transfusions. Antibiotics are used to fight off the pathogenic organisms and the gammaglobulin helps provide a normal balance of antibodies to fight the infection. Bone marrow transplantation may be an option in some cases.

OMIM: 308230

The visible signs and symptoms of MPS II in younger people are usually the first clues leading to a diagnosis. In general, the time of diagnosis usually occurs about 2 to 4 years of age. Doctors may use laboratory tests to provide additional evidence that an MPS disorder is present, before making a definitive diagnosis, by measuring the iduronate-2-sulfatase (I2S) enzyme activity. The most commonly used laboratory screening test for an MPS disorder is a urine test for GAGs. The urine test for GAGs can occasionally be normal, yet the child still may have an MPS disorder. A definitive diagnosis of Hunter syndrome is made by measuring I2S activity in serum, white blood cells, or fibroblasts from skin biopsy. In some people with Hunter syndrome, analysis of the" I2S" gene can determine clinical severity. Prenatal diagnosis is routinely available by measuring I2S enzymatic activity in amniotic fluid or in chorionic villus tissue.

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.

Diagnosis for "type 1" of this condition for example, sees that the following methods/tests are available:

- Endoscopic

- CT scan

- Histologic test

Not all genetic disorders directly result in death, however there are no known cures for genetic disorders. Many genetic disorders affect stages of development such as Down syndrome. While others result in purely physical symptoms such as muscular dystrophy. Other disorders, such as Huntington's disease show no signs until adulthood. During the active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy. This includes physical therapy, pain management, and may include a selection of alternative medicine programs.

The activity of arylsulfatase E can be measured with the substrate 4-methylumbelliferyl sulfate.

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.

Five "types" of hyper IgM syndrome have been characterized:

- Hyper-IgM syndrome type 1 (X-linked), characterized by mutations of the "CD40LG" gene. In this type, T cells cannot tell B cells to switch classes.

- Hyper-IgM syndrome type 2 (autosomal recessive), characterized by mutations of the "AICDA" gene. In this type, B cells cannot recombine genetic material to change heavy chain production

- Hyper-IgM syndrome type 3 characterized by mutations of the "CD40" gene. In this type, B cells cannot receive the signal from T cells to switch classes.

- Hyper-IgM syndrome type 4 which is a defect in class switch recombination downstream of the AICDA gene that does not impair Somatic Hypermutation.

- Hyper-IgM syndrome type 5 characterized by mutations of the "UNG" gene.

For this condition, differential diagnosis sees that the following should be considered:

- CD25 deficiency

- STAT5b deficiency

- Severe immunodeficiency(combined)

- X-linked thrombocytopenia

Orofaciodigital syndrome type 1 is diagnosed through genetic testing. Some symptoms of Orofaciodigital syndrome type 1 are oral features such as, split tongue, benign tumors on the tongue, cleft palate, hypodontia and other dental abnormalities. Other symptoms of the face include hypertelorism and micrognathia. Bodily abnormalities such as webbed, short, joined, or abnormally curved fingers and toes are also symptoms of Orofaciodigital syndrome type 1. The most frequent symptoms are accessory oral frenulum, broad alveolar ridges, frontal bossing, high palate, hypertelorism, lobulated tongue, median cleft lip, and wide nasal bridge. Genetic screening of the OFD1 gene is used to officially diagnose a patient who has the syndrome, this is detected in 85% of individuals who are suspected to have Orofaciodigital syndrome type 1.

The current (2008) diagnostic criteria for HLH are

1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11.

OR

2. Fulfillment of five out of the eight criteria below:

- Fever (defined as a temperature >100.4 °F, >38 °C)

- Enlargement of the spleen

- Decreased blood cell counts affecting at least two of three lineages in the peripheral blood:

- Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml) (anemia)

- Platelets <100×10/L (thrombocytopenia)

- Neutrophils <1×10/L (neutropenia

- High blood levels of triglycerides (fasting, greater than or equal to 265 mg/100 ml) and/or decreased amounts of fibrinogen in the blood (≤ 150 mg/100 ml)

- Ferritin ≥ 500 ng/ml

- Haemophagocytosis in the bone marrow, spleen or lymph nodes

- Low or absent natural killer cell activity

- Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)

In addition, in the case of familial HLH, no evidence of malignancy should be apparent.

It should be noted that not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis as delays results in increased mortality. The diagnostic criteria were developed in pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individual's risk of HLH.

The assessment for Smith-Finemen-Myers syndrome like any other mental retardation includes a detailed family history and physical exam that tests the mentality of the patient. The patient also gets a brain and skeletal imaging though CT scans or x-rays. They also does a chromosome study and certain other genetic biochemical tests to help figure out any other causes for the mental retardation.

The diagnosis of SFMS is based on visible and measurable symptoms. Until 2000, SFMS was not known to be associated with any particular gene. As of 2001, scientists do not yet know if other genes are involved in this rare disease. Generic analysis of the ATRX gene may prove to be helpful in diagnosis of SFMS.

Recent studies have found that the life expectancy of males with XLT is not significantly affected. Individuals with XLT typically experience milder symptoms than those with other "WAS"-related disorders. For this reason, the long term prognosis for individuals with XLT is generally positive as long as symptoms are managed appropriately. Enhanced treatment methods in the past two decades have significantly improved the prognosis as well.