Pyruvate Kinase Deficiency Natural History Study

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:

1. To estimate the transfusion burden in splenectomized and non-splenectomized participants
with PKD.

2. To establish a patient registry as a potential source for recruitment to future research
studies in PKD.

Secondary Objectives:

1. 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;

2. To describe changes over time in the range of hemoglobin values and markers of hemolysis
within individual participants and among participants with PKD;

3. To estimate the incidence of past splenectomy and annual splenectomy rate, as treatment
for PKD;

4. 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;

5. 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;

6. To determine pregnancy outcomes among participants with PKD;

7. To describe genotypic and phenotypic variation among participants and explore
genotype-phenotype correlation in PKD.

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.