Clinical trial NCT06278337: X-linked Moesin Associated Immunodeficiency
Official title: Etude Multicentrique Internationale rétrospective Des Patients Atteints de déficit Immunitaire associé à la moésine lié au Chromosome X (X Maid Pour X-linked Moesin Associated Immunodeficiency)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Immune Deficiency
Autoimmune Diseases
Infections
Diagnosis
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2024-02-26
Enrollment: 16
Sex: MALE
Minimum age (years): 4
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Given the small number of participants and the purpose of the study, the group may include deceased patients (at least 1 of the 16 participants). The sample size is 16 patients already identified, and possibly other patients who may be identified once the existence of the the existence of the international registry. Final enrolment will correspond to all X-MAID patients diagnosed worldwide who agree to take part in the study.

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

Eligibility criteria: Inclusion Criteria:

* Male patient with a mutation in the MOESIN gene (MSN)
* No objection to the collection of personal health data

Exclusion Criteria:

-

Primary outcomes:
measure: The main objective
timeFrame: through study completion, and average 3 years
Secondary outcomes:
measure: Secondary objectives1
timeFrame: through study completion, and average 3 years
Other outcomes:
measure: secondary objectives 2
timeFrame: through study completion, and average 3 years
measure: secondary objective 3
timeFrame: 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
measure: secondary objectives 4
timeFrame: Among patients diagnosed in the first years of life, none showed developmental defects.
measure: secondary objective 5
timeFrame: 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.
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Philadelphia
country: United States
facility: Perelman School of medecine
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Brisbane
country: Australia
facility: Genomic Research Centre, School of Biomedical Sciences Institute of Health and Biomedical Innovation
city: Bruxelles
country: Belgium
facility: Hôpital Universitaire de la Reine Fabiola
city: Paris
country: France
facility: Hôpital Necker
city: Rennes
country: France
facility: CHU Rennes, CNRS UMR 629
city: Saint-Étienne
country: France
facility: CHU St Etienne Hôpital Nord
city: Bunkyō-Ku
country: Japan
facility: Tokyo Medical and Dental University (TMDU)
city: Rotterdam
country: Netherlands
facility: Departments of Internal Medicine and Immunology
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Isabelle ANDRE, doctor
role: PRINCIPAL_INVESTIGATOR
References: