Viewing Study NCT05300360



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Last Modification Date: 2024-10-26 @ 2:28 PM
Study NCT ID: NCT05300360
Status: UNKNOWN
Last Update Posted: 2022-03-29
First Post: 2022-03-18

Brief Title: Prevalence of Adenosine Deaminase ADA Enzyme Deficiency Disease in Adult Patients With Pulmonary Alveolar Proteinosis
Sponsor: TRPHARM
Organization: TRPHARM

Study Overview

Official Title: Prospective Observational Study Evaluating the Prevalence of Adenosine Deaminase ADA Enzyme Deficiency Disease in Adult Patients With Pulmonary Alveolar Proteinosis in Pulmonology Clinics
Status: UNKNOWN
Status Verified Date: 2022-03
Last Known Status: ENROLLING_BY_INVITATION
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: This observational study was designed as a prospective epidemiological screening study Patients who have applied to the centers participating in the study and who have previously been clinically or pathologically diagnosed with PAP Pulmonary alveolar proteinosis will be included in the study Up-to-date data will be collected from patients who have agreed to participate in the study and a blood sample with DBS will be taken from patients The blood taken will be subjected to analysis for ADA metabolites For patients with a high metabolic test the responsible researcher will advise on clarifying the diagnosis with a genetic test other than the study In case of formation of new information for each patient consultation will be provided by the responsible researcher Thus the prevalence of ADA enzyme deficiency disease will be evaluated in patients diagnosed with PAP
Detailed Description: PAP Pulmonary alveolar proteinosis is a rare disease with a frequency of 036 per million As a result of intensive accumulation of surfactant components in the lungs it leads to respiratory distress at various levels PAP has been frequently monitored among patients with ADA enzyme deciency Primary immunodeficiency diseases are a group of diseases that are accompanied by chronic andor recurrent bacterial fungal protozoal and viral infections that develop as a result of primary or congenital immunodeficiency The incidence dec in society varies from 110000 to 1100000 Combined immunodeficiencies account for 15-29 of primary immunodeficiencies Severe Combined Immunodeficiencies SCID are a heterogeneous group of diseases caused by hereditary errors in genes involved in the development andor function of T B and sometimes NK cells which cause serious dysfunction of the immune system The incidence is estimated at 1100000 live births in the United States Although the exact incidence of inbreeding is not known in our country where inbreeding is common it is expected that those who show autosomal recessive transition will be more common especially The recognition of these disorders by clinicians is important for reducing long-term complications due to recurrent infections and preventing mortality with appropriate treatment The frequency of SCIDY in our country is unknown Unlike in Europe and America SCID types which are autosomal recessive in our country are considered to be the most common form due to the high rates of inbreeding The ratio obtained by comparing the number of live babies born in a year in Konya with the number of SCID cases diagnosed in the same year in the Pediatric Immunology Clinic of the Meram Faculty of Medicine of Selcuk University the only primary immunodeficiency diagnostic center in the region is 110000 This preliminary study shows that in our country this disease is much more common than in Europe and America To date more than 20 genetic defects have been identified that cause SCID All known genetic defects disrupt the development of cells of the immune system causing combined immunodeficiency One of them the ADA defect is also a metabolic disease due to which there is a lack of enzymes ADA catalyzes the deamination of purine nucleosides adenosine Ado and 2-deoxyadenosine dAdo which are produced during the degradation and transformation of RNA and DNA ADA is a cleansing enzyme it detoxifies purines In ADA deficiency 2-deoxyadenosine dAdo is phosphorylated and converted into deoxyadenosine triphosphate dATP Accumulation of DATP disrupts DNA repair and replication In ADA deficiency a high percentage of dATP accumulates especially in erythrocytes and lymphocytes Increased levels of adenosine break down the wall of the lymphocyte It inhibits the development of lymphocytes in the thymus A kind of lymphocyte intoxication occurs It leads to a severe form of lymphopenia Approximately 10-20 of SCID are diagnosed as ADA enzyme deficiency It shows an autosomal recessive transition Your gene is 20 it is localized on the long arm of the chromosome

Clinically there are early and late onset types

Classic-early onset ADA deficiency Although normal at birth patients present with infections seen from the first months of life resulting in death if left untreated In addition to the AKI table neuro-developmental disorders sensorineural hearing loss andor skeletal abnormalities have also been reported in these patients Although hematopoietic stem cell transplantation enzyme replacement therapy and gene therapy are treatment approaches that provide cure early diagnosis determines the prognosis

Late-onset ADA deficiency Patients may present with recurrent infections bronchiectasis autoimmunity human papillomavirus HPV infections at an older age even in adulthood Lymphopenia is an invariable finding High IgE and eosinophilia may be observed In these cases residual enzyme activity due to the type of mutation causes a late onset This phenotype accounts for 10-15 of all cases of ADA deficiency

Patients with late-onset ADA enzyme deficiency appear in the form of case reports in a study in which the data of two patients were shared in Zurich in 1997 one patient had a history of recurrent otitis and pulmonary infection bronchiectasis lymphopenia and immunoglobulin E elevation The other patient his cousin ADA was diagnosed by chance while undergoing a bone marrow scan due to enzyme deficiency He had a history of recurrent tonsillitis

In a study conducted by Hacettepe University published in 2018 The data of 13 ADA enzyme deficient patients were evaluated and it was determined that 3 patients with latedelayed diagnosis had ADA enzyme deficiency A patient with a late diagnosis of ADA enzyme deficiency was found to have recurrent pneumonia bronchiectasis and immunoglobulin E elevation

In the study in which the data of a patient with a late onset ADA enzyme deficiency published in Konya from our country in 2010 were shared it was observed that the patient had a history of resection of the lower left lobe due to bronchiectasis lymphopenia and an increase in immunoglobulin E

Diagnosis ADA enzyme deficiency is included in severe combined immunodeficiencies and is observed with lymphopenia and infections The diagnosis is made by measuring the activity of the enzyme ADA in erythrocytes or lymphocytes in patients with suspected clinical and laboratory features such as lymphopenia bronchiectasis By mutation analysis a gene defect is shown However T-cell receptor excision circles TREC test is used for early diagnosis However since the TREC test is found to be normal at birth in late-onset patients screening that leads patients to an early diagnosis can only be achieved by measuring ADA metabolites

In late-onset ADA deficiency it is difficult to diagnose Low awareness of the disease and its symptoms usually results in these cases not being diagnosed not being able to reach effective treatment permanent organ damage and patient loss For this reason diagnosis of patients is very important in terms of quality of life as well as vital importance

Reason ADA enzyme deficiencies account for approximately 15 of severe combined immunodeficiencies In 15-20 of patients with ADA enzyme deficiency ADA enzyme deficiency is observed with a late diagnosis Because of the inability of these patients to get a diagnosis their treatment is also inadequate For the first time in our country this study aims to determine the diagnosis and obtain preliminary data on the prevalence of ADA disease by looking at ADA metabolites in a group of adult patients diagnosed with PAP

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None