Pyruvate Kinase Deficiency Natural History Study

Study Overview
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Brief Summary
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The purpose of this study is to describe the range and incidence of symptoms, treatments, and complications related to pyruvate kinase deficiency (PKD). Eligible patients are those of all ages with known PKD or with a hemolytic anemia and a family member with PKD. The study will collect retrospective medical history, routine clinical care data, and quality of life measures at baseline and annually for patients with PKD.

Detailed Description
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The purpose of the Pyruvate Kinase Deficiency (PKD) Natural History Study is to describe the natural history of PKD and the range and incidence of symptoms, treatments, and complications related to PKD. The study will collect retrospective medical history and routine clinical care data at baseline and annually for patients with PKD. Patients without a genetic diagnosis will have a blood sample drawn for genetic diagnostic confirmation for research purposes. Understanding the clinical variation among participants with PKD, and assessing treatments specific to PKD and their outcomes will accelerate improvement in the care of patients with PKD. Understanding the natural history of PKD may be useful in the design of future interventional studies. Detailed genotypic and phenotypic characterization of the cohort will allow for continued in depth characterization of PKD. Finally, the PKD Natural History Study will identify interested participants for future PKD studies. Primary Objectives: To estimate the transfusion burden in splenectomized and non-splenectomized participants with PKD. To establish a patient registry as a potential source for recruitment to future research studies in PKD. Secondary Objectives: To determine if patient-reported outcomes, including quality of life and fatigue scales, are associated with age, genotype, hemoglobin nadir, and/or transfusion burden, overall and within the subgroups of splenectomized vs. non-splenectomized participants; To describe changes over time in the range of hemoglobin values and markers of hemolysis within individual participants and among participants with PKD; To estimate the incidence of past splenectomy and annual splenectomy rate, as treatment for PKD; To estimate the prevalence and severity and describe the treatment of hepatic and cardiac iron overload and its complications in PKD (liver, cardiac, growth defects, hypogonadotropic hypogonadism, and other endocrine defects). To describe the changes in these complications that may occur over time and by age group; To estimate the prevalence of co-morbidities associated with chronic hemolysis in PKD, to identify which co-morbidities are the most common, and to determine if the prevalence and/or severity of co-morbidities change over time and by age at the time of the first appearance of the co-morbidity; To determine pregnancy outcomes among participants with PKD; To describe genotypic and phenotypic variation among participants and explore genotype-phenotype correlation in PKD.

Official Title
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Pyruvate Kinase Deficiency (PKD) Natural History Study

Conditions
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Pyruvate Kinase Deficiency, Congenital Non-Spherocytic Hemolytic Anemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of all ages with biochemically or genetically diagnosed PKD. Patients with a hemolytic anemia AND a family member with genetically diagnosed PKD The participant or the guardian of the participant is willing and able to give written informed consent and/or assent. Exclusion Criteria: The participant or the guardian of the participant is unwilling or unable to give written informed consent and/or assent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pyruvate Kinase Deficiency<br>Patients of all ages with Pyruvate Kinase Deficiency | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| transfusion burden in splenectomized and non-splenectomized participants |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient-reported outcomes | EuroQoL-5D-5L, Functional Assessment of Cancer Therapy-Anemia (FACT-An), Pediatric Quality of Life Inventory 4.0 (pedsQL 4.0), Pediatric Functional Assessment of Chronic Illness-Fatigue (pedsFACIT-F), Patient Reported Outcomes Measurement Information System Fatigue (PROMIS Fatigue) | enrollment, annually, up to 2 years | 
| changes over time in hemoglobin and markers of hemolysis |  | enrollment, annually, up to 2 years | 
| prevalence and severity of iron overload |  | enrollment, annually, up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pyruvate kinase deficiency, hemolytic anemia, anemia, enzymopathy, jaundice, splenectomy, health-related quality of life, Hematologic diseases