The underlying causes of CVID are largely obscure. Genetic mutations can be identified as the cause of disease in about 10% of people, while familial inheritance accounts for 10–25% of cases. Rather than arising from a single genetic mutation, CVID seems to result from variety of mutations that all contribute to a failure in antibody production. Mutations in the genes encoding ICOS, TACI, CD19, CD20, CD21, CD80 and BAFFR have been identified as causative of CVID. Susceptibility to CVID may also be linked to the major histocompatibility complex (MHC) of the genome, particularly to DR-DQ haplotypes. A mutation in the NFKB2 gene has recently been shown to cause CVID-like symptoms in a murine model. The frequency of this NFKB2 mutation in the CVID population is, however, yet to be established. Diagnosis
According to a European registry study, the mean age at onset of symptoms was 26.3 years old. As per the criteria laid out by ESID (European Society for Immunodeficiencies) and PAGID (Pan-American Group for Immunodeficiency), CVID is diagnosed if:
the person presents with a marked decrease of serum IgG levels (<4.5 g/L) and a marked decrease below the lower limit of normal for age in at least one of the isotypes IgM or IgA;
the person is four years of age or older;
the person lacks antibody immune response to protein antigens or immunization.Diagnosis is chiefly by exclusion, i.e. alternative causes of hypogammaglobulinemia, such as X-linked agammaglobulinemia, must be excluded before a diagnosis of CVID can be made.
For example, an individual who has been diagnosed with associative agnosia in the visual modality would not be able to match pictures of a laptop that is open with a laptop that is closed. Pure alexia
Individuals with pure alexia usually have difficulty reading words as well as difficulty with identifying letters. In order to assess whether an individual has pure alexia, tests of copying and recognition must be performed. An individual with pure alexia should be able to copy a set of words, and should be able to recognize letters. Prosopagnosia
Individuals are usually shown pictures of human faces that may be familiar to them such as famous actors, singers, politicians or family members. The pictures shown to the patient are selected to be age and culture appropriate. The task involves the examiner asking the individual to name each face. If the individual cannot name whose face appears in the picture, the examiner may ask a question that would help to recognize the face in the picture. Treatment
For all practical purposes, there is no direct cure. Patients may improve if information is presented in other modalities than the damaged one. Different types of therapies can help to reverse the effects of agnosia. In some cases, occupational therapy or speech therapy can improve agnosia, depending on its cause.Initially many individuals with a form of agnosia are unaware of the extent to which they have either a perceptual or recognition deficit. This may be caused by anosognosia which is the lack of awareness of a deficit.