Congenital Hemolytic and Dyserythropoietic Anemias

The main reason for this research study is to further understand how some red blood cells are formed incorrectly or they have an abnormal metabolism in a way that they break easier in the circulation or during their passage through the spleen.

Participants and/or family members diagnosed with non-immune hemolytic anemia due to a genetic disorder, such as, hemoglobin disorder, erythrocyte membrane skeleton disorders (e.g. spherocytosis, elliptocytosis, or stomatocytosis) or hydration defect (e.g. xerocytosis, overhydrocytosis) or red blood cell (RBC) enzyme disorders, or with a congenital dyserythropoietic anemia (CDA) will be asked to participate.

Study Overview

• Status: Recruiting
• Conditions: Hemolytic Anemia

Detailed Description

The purpose of this study is to explore for known or yet unknown genetic mutations causative for non-immune hemolysis and/or anemia, in patients with hemoglobin disorders, membrane skeleton defects (a group of diseases including hereditary spherocytosis, hereditary elliptocytosis and pyropoikilocytosis, and hereditary stomatocytosis syndromes), RBC enzymopathies (most common of them being glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase deficiency), and congenital dyserythropoietic anemias. The goal is to optimize genetic diagnosis for patients with non-immune congenital hemolytic anemias, and advance research on the pathogenesis and potentially improve treatment options for these rare disorders. We include analysis for genes that are known or suspected to participate in the making of healthy red blood cells. Sequencing analysis of the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) is also included because the clinical care of these patients frequently necessitate such testing to evaluate for increased risk of cholelithiasis, due to co-inheritance of Gilbert syndrome.

This is a non-interventional study, focusing on improving diagnosis and understanding the mechanisms of how abnormalities of genes may affect the making and survival of red blood cells.

The traditional tests that usually suggest the diagnosis of an erythrocyte cytoskeleton defect or a RBC enzymopathy (erythrocyte morphology in the blood smear, osmotic fragility test, and ektacytometry or enzyme activity assay respectively) do not always provide a definitive diagnosis, especially because the diagnosis with those methods requires a pure population of the patient's red blood cells, obtainable three months after last PRBC transfusion, and is therefore complicated or impossible in the patients who need frequent transfusions. Erythrocyte membrane proteins can be prepared from washed red blood cells or potentially from isolated reticulocytes from the patient. Analysis of such sample by electrophoresis on polyacrylamide gel followed by western blot for specific proteins can be a valuable tool that orients towards the diagnosis and may point to the specific gene responsible for the disease.

We propose a systematic approach to improve diagnostic evaluation of such diseases by completing a parallel analysis of ektacytometry, erythrocyte membrane proteins electrophoresis and western blot along with full exon sequencing using genomic DNA from isolated white blood cells in blood samples donated from approximately 400 patients and their parents. Our goal is to identify specific mutation(s) responsible for the patients' congenital hemolytic or dyserythropoietic anemia, and develop a genetic approach to the diagnosis of such diseases. In addition, such genetic data will offer valuable information towards understanding the pathogenesis of this group of diseases.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Amy Shova; Phone Number: 513-803-1917; Email: amy.shova@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

If medical history and review of the laboratory data obtained for clinical care, including CBC/reticulocyte count and review of the blood smear, indicates that the patient has a non-immune hemolytic anemia that may be due to a hemoglobinopathy, a red cell membrane skeleton or enzyme disorder, then the patients and their families will be asked for their participation in the study. The rare patients suspected to have congenital dyserythropoietic anemia will also be eligible for this study.

Description

Inclusion Criteria:

1. Patients who have been diagnosed, by medical history and review of the laboratory data obtained for clinical care, including CBC/reticulocyte count and review of the blood smear, with a hereditary hemolytic anemia, where the genetic etiology is challenging to be identified.
2. Parents and/or grandparents of children that have the above diagnosis. The parents and/or grandparents may or may not have non-immune hemolytic anemia (these will serve as positive or negative inherent controls)

Exclusion:

1) Patients with anemias known to be acquired and not associated with a genetic etiology.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with an Established Molecular Diagnosis of a Red Blood Cell Disorder	The proportion of participants in whom a molecular diagnosis is established through genetic and laboratory evaluation, defined as identification of pathogenic or likely pathogenic variants associated with hereditary hemolytic anemia (including hemoglobin disorders, erythrocyte membrane disorders, and red blood cell enzymopathies) or dyserythropoietic anemia.	From enrollment to completion of molecular and diagnostic evaluation (approximately 12-24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Identified Novel Genetic Variants Associated with Red Blood Cell Disorders	The number of participants in whom previously unreported or novel genetic variants or novel candidate genes potentially associated with red blood cell disorders are identified through molecular testing.	From enrollment to completion of molecular and diagnostic evaluation (approximately 12-24 months)
Description of Genotype-Phenotype Associations in Participants with Red Blood Cell Disorders	Assessment of the relationship between identified genetic variants and clinical and laboratory features, including effects on red blood cell production, morphology, and survival. Results will be summarized descriptively.	From enrollment to completion of molecular and diagnostic evaluation (approximately 12-24 months)

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2011
• Primary Completion (Estimated): July 1, 2050
• Study Completion (Estimated): July 1, 2052

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: June 12, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Hemic and Lymphatic Diseases; Anemia, Hemolytic
• Other Study ID Numbers: Congenital Hem/2011-1510

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No