An absolute neutrophil count (ANC) chronically less than 500/mm3, usually less than 200/mm3, is the main sign of Kostmann's. Other elements include the severity of neutropenia, the chronology (from birth; not emerging later), and other normal findings (hemoglobin, platelets, general body health). Isolated neutropenia in infants can occur in viral infections, autoimmune neutropenia of infancy, bone marrow suppression from a drug or toxin, hypersplenism, and passive placental transfer of maternal IgG.

A bone marrow test can assist in diagnosis. The bone marrow usually shows early granulocyte precursors, but myelopoietic development stops ("arrests") at the promyelocyte and/or myelocyte stage, so that few maturing forms are seen. Neutrophil survival is normal.

Needs mention of (rarer) myelokathexis types. e.g. G6PC3 variant and

Generally accepted reference range for absolute neutrophil count (ANC) in adults is 1500 to 8000 cells per microliter (µl) of blood. Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/µl):

- Mild neutropenia (1000 <= ANC < 1500): minimal risk of infection

- Moderate neutropenia (500 <= ANC < 1000): moderate risk of infection

- Severe neutropenia (ANC < 500): severe risk of infection.

Each of these are either derived from laboratory tests or via the formula below:

ANC = formula_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 blood count typically shows decreased numbers of blood cells—including a decreased amount of circulating red blood cells, white blood cells, and platelets.

The bone marrow may show hemophagocytosis.

The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.

The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.

The serum fibrinogen level is usually low and the D-dimer level is elevated.

The sphingomyelinase is elevated.

Bone marrow biopsy shows histiocytosis.

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.

Typically, a diagnosis of DBA is made through a blood count and a bone marrow biopsy.

A diagnosis of DBA is made on the basis of anemia, low reticulocyte (immature red blood cells) counts, and diminished erythroid precursors in bone marrow. Features that support a diagnosis of DBA include the presence of congenital abnormalities, macrocytosis, elevated fetal hemoglobin, and elevated adenosine deaminase levels in red blood cells.

Most patients are diagnosed in the first two years of life. However, some mildly affected individuals only receive attention after a more severely affected family member is identified.About 20–25% of DBA patients may be identified with a genetic test for mutations in the RPS19 gene.

Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term.

Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival.

Neutropenia that is developed in response to chemotherapy typically becomes evident in seven to fourteen days after treatment. Conditions that indicate the presence of neutropenic fever are implanted devices; leukemia induction; the compromise of mucosal, mucociliary and cutaneous barriers; a rapid decline in absolute neutrophil count, duration of neutropenia >7–10 days, and other illnesses that exist in the patient.

Signs of infection in patients can be subtle. Fevers are a common and early observation. Sometimes overlooked is the presence of hypothermia, which can be present in sepsis. Physical examination and accessing the history and physical examination is focussed on sites of infection. Indwelling line sites, areas of skin breakdown, sinuses, nasopharynx, bronchi and lungs, alimentary tract, and skin are assessed.

The diagnosis of neutropenia is done via the low neutrophil count detection on a full blood count. Generally, other investigations are required to arrive at the right diagnosis. When the diagnosis is uncertain, or serious causes are suspected, bone marrow biopsy may be necessary. Other investigations commonly performed: serial neutrophil counts for suspected cyclic neutropenia, tests for antineutrophil antibodies, autoantibody screen (and investigations for systemic lupus erythematosus), vitamin B and folate assays. Rectal examinations are usually not performed due to the increased risk of introducing bacteria into the blood stream and the possible development of rectal abscesses. A routine chest X-ray and urinalysis may be can not be relied upon or considered normal due to the absence of neutrophils.

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)

The diagnosis is made after a complete blood count, a routine blood test. The absolute neutrophil count in this test will be below 500, and can reach 0 cells/mm³. Other kinds of blood cells are typically present in normal numbers.

To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia and leukemias. This requires a bone marrow examination that shows normocellular (normal amounts and types of cells) blood marrow with underdeveloped promyelocytes. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.

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.

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.

In some cases, the direct coombs will be negative but severe, even fatal HDN can occur. An indirect coombs needs to be run in cases of anti-C, anti-c, and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN.

There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling. Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.

- Free Cell DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas.

- Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells.

- CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.

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 cause of Felty's syndrome is unknown, but it has been found to be more common in those with chronic rheumatoid arthritis. Some patients have Human Leukocytic Antigen (HLA-DR4) in their serum. This syndrome is mostly present in people having extra articular manifestations of rheumatoid arthritis. People with this syndrome are at risk of infection because they have a low white blood cell count.

In developing new chemotherapeutics（化疗方法），the efficacy of the drug against the disease is often balanced against the likely level of myelotoxicity the drug will cause. In-vitro colony forming cell (CFC) assays using normal human bone marrow grown in appropriate semi-solid media such as ColonyGEL have been shown to be useful in predicting the level of clinical myelotoxicity a certain compound might cause if administered to humans. These predictive in-vitro assays reveal effects the administered compounds have on the bone marrow progenitor cells that produce the various mature cells in the blood and can be used to test the effects of single drugs or the effects of drugs administered in combination with others.

A complete blood count (CBC) can be done to diagnose anemia (normochromic, normocytic), thrombocytopenia, and neutropenia. Abnormal liver function tests are commonly used to help in diagnosis as the spleen and liver are strongly affected by one another.

Bone marrow suppression due to anti-cancer chemotherapy is much harder to treat and often involves hospital admission, strict infection control, and aggressive use of intravenous antibiotics at the first sign of infection.

G-CSF is used clinically (see Neutropenia) but tests in mice suggest it may lead to bone loss.

GM-CSF has been compared to G-CSF as a treatment of chemotherapy-induced myelosuppression/Neutropenia.

The Multinational Association for Supportive Care in Cancer (MASCC) risk index can be used to identify low-risk patients (score ≥21 points) for serious complications of febrile neutropenia (including death, intensive care unit admission, confusion, cardiac complications, respiratory failure, renal failure, hypotension, bleeding, and other serious medical complications). The score was developed to select patients for therapeutic strategies that could potentially be more convenient or cost-effective. A prospective trial demonstrated that a modified MASCC score can identify patients with febrile neutropenia at low risk of complications, as well.

In contrast, the Clinical Index of Stable Febrile Neutropenia (CISNE) score is specific of patients with solid tumors and seemingly stable episodes. CISNE is able to discriminate groups of patients who are at low, intermediate, and high risk of complications in this population. With the CISNE, the complication rate was determined to be 1.1% for low-risk patients, 6.2% for intermediate-risk patients, and 36.0% for high-risk patients. The prime purpose of this model was to avoid complications from an early hospital release. On the contrary, CISNE should not be used so much to select low-risk patients for outpatient treatment.

Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

The diagnosis is confirmed by bone marrow smears that show "giant inclusion bodies" in the cells that develop into white blood cells (leukocyte precursor cells). CHS can be diagnosed prenatally by examining a sample of hair from a fetal scalp biopsy or testing leukocytes from a fetal blood sample.

Under light microscopy the hairs present evenly distributed, regular melanin granules, larger than those found in normal hairs. Under polarized light microscopy these hairs exhibit a bright and polychromatic refringence pattern.

This form usually lessens in severity within two years of diagnosis.

The use of prophylactic antibiotics has been proposed.

See article at BioMed Central site:

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.

Initially, the clinical presentation of SDS may appear similar to cystic fibrosis. However, CF can be excluded with a normal chloride in sweat test but faecal elastase as a marker of pancreatic function will be reduced. The variation, intermittent nature, and potential for long-term improvement of some clinical features make this syndrome difficult to diagnose. SDS may present with either malabsorption, or hematological problems. Rarely, SDS may present with skeletal defects, including severe rib cage abnormalities that lead to difficulty in breathing. Diagnosis is generally based on evidence of exocrine pancreatic dysfunction and neutropenia. Skeletal abnormalities and short stature are characteristics that can be used to support the diagnosis. The gene responsible for the disease has been identified and genetic testing is now available. Though useful in diagnostics, a genetic test does not surmount the need for careful clinical assessment and monitoring of all patients.