Ignite Creation Date:
2024-05-06 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 2:28 PM
Study NCT ID:
NCT05300373
Status:
UNKNOWN
Last Update Posted:
2022-03-29
First Post:
2022-03-18
Brief Title:
Evaluation of Adenosine Deaminase ADA Enzyme Deficiency in Patients With Lymphopenia andor Elevated Immunoglobulin E
Sponsor:
TRPHARM
Organization:
TRPHARM
Study Overview
Official Title:
Prospective Observational Study Evaluating the Prevalence of Adenosine Deaminase ADA Enzyme Deficiency Disease in Patients With Lymphopenia andor Immunoglobulin E Elevation in Adult Immunology and Hematology 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 study was designed as an observational prospective epidemiological screening study Patients who have been admitted to the center and whose lymphopenia andor Immunoglobulin E elevation has been detected in at least one examination in their medical history will be included
In accordance with the relevant legislation patients are required to accept and sign the Informed Consent Form regarding their participation in the study
Current data that the physician has already questioned in his daily practice will be collected from patients who have agreed to participate in the study and a blood sample will be taken from patients on Guthrie paper This sample will be prepared by taking it from the patient as the physician deems appropriate dripping it into a special area designated on Guthrie paper and drying it
The test result will be sent to the researcher by e-mail 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 in patients with lymphopenia will be evaluated In addition with this study it will be scientifically demonstrated whether lymphopenia is a parameter that facilitates early diagnosis of ADA patients
In accordance with the relevant legislation patients are required to accept and sign the Informed Consent Form regarding their participation in the study
Current data that the physician has already questioned in his daily practice will be collected from patients who have agreed to participate in the study and a blood sample will be taken from patients on Guthrie paper This sample will be prepared by taking it from the patient as the physician deems appropriate dripping it into a special area designated on Guthrie paper and drying it
The test result will be sent to the researcher by e-mail 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 in patients with lymphopenia will be evaluated In addition with this study it will be scientifically demonstrated whether lymphopenia is a parameter that facilitates early diagnosis of ADA patients
Detailed Description:
Primary immunodeficiencies are encountered with signs and symptoms related to various disciplines of medicine and are detected more often in our country than in other societies
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 USA 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 Each step that is effective in the emergence of an immune response creates the potential for a primary immunodeficiency disease Due to the development of molecular and cellular techniques the possibility of prenatal diagnosis has arisen with the detection of localization and mutations of the defective gene in various immunodeficiencies 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 SCID 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 figure 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 at 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 About 1300 a year in our countryconsidering that 000 babies have been born it should be expected that 140 new cases of SCID should be encountered every year The number of cases diagnosed in our country is much lower than this figure
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 AKIS 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 SCI 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 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
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 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
Although studies are continuing for SCID which has not yet been included in the screening program in our country the tandem mass spectrometer which can be used to diagnose ADA deficiency is used in newborn screening programs for metabolic diseases Studies of newborn screening with a tandem mass spectrometer for ADA and PNP deficiencies which is also a metabolic disease began after 2010 and it has been shown that this method is a low-cost and reliable method Early and late onset ADA deficiency cases can be detected with sensitivity and specificity reaching 100 with this method
Importance of early diagnosis In Early Onset ADA deficiency patients usually consult a doctor with signs of infections The fact that infections are already common in the dairy childhood age group makes diagnosis difficult If there is no similar case in the family that has been diagnosed before or if this is not paid attention to in the history the diagnosis of the cases is delayed In late-onset ADA deficiency the diagnosis is much more difficult Low awareness of the disease and its symptoms usually results in these cases not being diagnosed not being able to get effective treatment and organ damage For this reason early diagnosis is very important in terms of quality of life as well as vital importance
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 USA 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 Each step that is effective in the emergence of an immune response creates the potential for a primary immunodeficiency disease Due to the development of molecular and cellular techniques the possibility of prenatal diagnosis has arisen with the detection of localization and mutations of the defective gene in various immunodeficiencies 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 SCID 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 figure 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 at 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 About 1300 a year in our countryconsidering that 000 babies have been born it should be expected that 140 new cases of SCID should be encountered every year The number of cases diagnosed in our country is much lower than this figure
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 AKIS 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 SCI 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 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
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 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
Although studies are continuing for SCID which has not yet been included in the screening program in our country the tandem mass spectrometer which can be used to diagnose ADA deficiency is used in newborn screening programs for metabolic diseases Studies of newborn screening with a tandem mass spectrometer for ADA and PNP deficiencies which is also a metabolic disease began after 2010 and it has been shown that this method is a low-cost and reliable method Early and late onset ADA deficiency cases can be detected with sensitivity and specificity reaching 100 with this method
Importance of early diagnosis In Early Onset ADA deficiency patients usually consult a doctor with signs of infections The fact that infections are already common in the dairy childhood age group makes diagnosis difficult If there is no similar case in the family that has been diagnosed before or if this is not paid attention to in the history the diagnosis of the cases is delayed In late-onset ADA deficiency the diagnosis is much more difficult Low awareness of the disease and its symptoms usually results in these cases not being diagnosed not being able to get effective treatment and organ damage For this reason early diagnosis is very important in terms of quality of life as well as vital importance
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