Clinical Guidance

Males with CD40 ligand deficiency show remarkable variability in clinical symptoms. No specific genotype-phenotype correlations for CD40LG have been identified . However, the and pathogenic variants have been reported in unrelated families with milder and later-onset disease . Whether or not this is a true association needs to be evaluated with study of additional families with these pathogenic variants.

Source: GeneReviews — "CD40 Ligand Deficiency"

Diagnostic Criteria

Suggestive Findings

CD40 ligand deficiency should be suspected in any male presenting with Pneumocystis jirovecii pneumonia, persistent Cryptosporidium diarrhea, recurrent upper- and lower-respiratory tract bacterial infections, neutropenia, or sclerosing cholangitis and associated bile duct tumors with the following laboratory abnormalities:

• Absent or low serum concentrations of immunoglobulin (Ig) G and IgA

• Normal or elevated serum concentrations of IgM

• Normal number and distribution of T, B, and NK lymphocyte subsets

• Normal T-cell proliferation in response to mitogens

• Decreased expression of CD40 ligand (CD40L) on the surface of activated CD4 cells (not universal)

Establishing the Diagnosis

The diagnosis of CD40 ligand deficiency is established in a male proband with typical clinical and la...

Source: GeneReviews — "CD40 Ligand Deficiency"

Differential Diagnosis

Genetic disorders of interest in the differential diagnosis of CD40 ligand deficiency are listed in . Table 2. CD40 Ligand Deficiency: Differential Diagnosis

Management Guidelines

No clinical practice guidelines for CD40 ligand deficiency have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with CD40 ligand deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

CD40 Ligand Deficiency: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Hematology/

Immunology

| • CBC w/differential

• IgG levels

• T, B, NK cell numbers

| For evidence of cytopenias

Pulmonary

| Baseline chest radiograph pulmonary function testing | For chronic lung changes due to infection; if present, consider pulmonology eval.

Gastrointestinal

| PCR-based testing of stools | For presence of Cryptosporodium or other enteric pathogens; if present, partner w/gastroenterologist.

Nutritional assessment |

Hepatobiliary

| Baseline liver function testing liver/ biliary tree ultrasound | For evidence of hepatocyte dysfunction developing biliary dilatation

Transplantation

| All affected persons should be offered HLA typing at diagnosis. | For consideration of HSCT

Genetic counseling

| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of CD40 ligand deficiency to facilitate medical personal decision making

Source: GeneReviews — "CD40 Ligand Deficiency"

Clinical Guidance

Avoid areas that place the individual at risk of contracting Cryptosporidium including pools, lakes, ponds, or certain water sources. Avoid drinking unpurified or unfiltered water. Live vaccines such as rotavirus, MMR (measles, mumps, and rubella), varicella, live attenuated polio, and BCG (bacillus Calmette-Gurin for tuberculosis) should not be given to individuals with CD40 ligand deficiency.

Source: GeneReviews — "CD40 Ligand Deficiency"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "CD40 Ligand Deficiency"

Surveillance Guidelines

No guidelines have been published for ongoing surveillance in individuals with CD40 ligand deficiency. presents the current recommendations of the authors. Table 5. CD40 Ligand Deficiency: Recommended Surveillance

Source: GeneReviews — "CD40 Ligand Deficiency"