Autoimmune Diseases, Diagnosis, Immune Deficiency, Infections
Conditions
Brief summary
Moesin deficiency was initially described in 7 male participants aged 4 to 69 years and is characterized by lymphopenia of the 3 lineages and moderate neutropenia. Genetically, 6 out of 7 participants had the same missense mutation in the moesin gene located on the X chromosome. The 7th patient has a mutation leading to the premature introduction of a STOP codon into the protein.Clinically the 7 participants with X-linked moesin-associated immunodeficiency all presented with recurrent bacterial infections of the respiratory, gastrointestinal or urinary tracts, and some had severe varicella.Therapeutically, in the absence of a molecular diagnosis and due to his SCID-like phenotype, one patient was treated with geno-identical hematopoietic stem cell transplantation . The remaining are untreated or treated with immunoglobulin substitution and/or prophylactic antibiotics. Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The Investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigator propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each patient according to his or her clinical picture
Detailed description
Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigators propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each participant according to his or her clinical picture
Interventions
GENETICgenetic restrospective study
it is not an interventional study but observational
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
4 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male patient with a mutation in the MOESIN gene (MSN) * No objection to the collection of personal health data
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The main objective | through study completion, and average 3 years | The main objective is to study the clinical results of the different therapeutic options applied to X-MAID patients, and to investigate whether there is a correlation between treatment responses and mutation position |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary objectives1 | through study completion, and average 3 years | Circumstances of genetic diagnosis: at what age are these patients diagnosed, and by what means? (role of prenatal screening). |
Other
| Measure | Time frame | Description |
|---|---|---|
| secondary objectives 2 | through study completion, and average 3 years | What is the state of their immune system and, depending on this state, the CID or SCID classification of the disease. |
| secondary objective 3 | All the patients are male. As a result of their immune deficiency, patients suffer from recurrent bacterial infections of the respiratory, digestive and urinary tracts, as well as, in some cases, skin manifestations such as eczema, alopecia and molluscum | What are the clinical manifestations of the disease (cutaneous, infectious, autoimmune)? |
| secondary objectives 4 | Among patients diagnosed in the first years of life, none showed developmental defects. | What impact does the disease have on their development? |
| secondary objective 5 | Treatments range from no prophylaxis at all to antibiotic prophylaxis, with or without immunoglobulin therapy, granulocyte-colony-stimulating factor therapy or hematopoietic stem cell allograft. | What are the treatments and their consequences? |
Countries
Australia, Belgium, France, Japan, Netherlands, United States
Contacts
Primary ContactIsabelle ANDRE, Doctor
Outcome results
None listed