PK deficiency Variations in Case Studies | For HCPs

Case Studies


Explore these case profiles to find out more about the consequences of misdiagnosis as well as symptoms and complications over time.

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Unexplained periods of sickness
Testing for general anemia, aplastic anemia, sickle cell anemia
Age 25
Presented at hospital with extreme abdominal pain; confirmed splenomegaly and gallstones
Diagnosis of PK deficiency
Ages 25 to 35
Patient feels "fairly well"
Age 36
Patient presents with severe pain; iron overload is observed. Chelation therapy initiated
Age 58
Presented at hospital with severe hemolytic crisis; first transfusion given Splenectomy and cholecystectomy performed
*Due to the variability of the disease, case profiles are not reflective of every patient.

Inflammatory anemia, hyperbilirubinemia attributed to Gilbert syndrome (not confirmed by genetic testing)
Age 27
Baseline hemoglobin (Hb) improvement of 11.5 to 12.5 g/dL
Age 29
Markers of hemolysis
  • Hb: 10.9 g/dL (low)
  • Absolute reticulocyte count:
    1030 × 109/L (high)
  • Haptoglobin: undetectable
  • Indirect bilirubin: 3.7 mg/dL (high)
Additional evaluations
  • Direct antiglobulin test: negative
  • Hb electrophoresis: unremarkable
  • Erythrocyte membrane defects: negative
PK enzyme and genetic testing
PK activity: 1.2 U/g Hb (reference range, 6.7-14.3 U/g Hb)
Compound heterozygosity for 2 PKLR missense mutations
*Due to the variability of the disease, case profiles are not reflective of every patient.
Patients with PK deficiency can be diagnosed at any age.
Among patients enrolled in the Pyruvate Kinase Deficiency Natural History Study, age at diagnosis ranged from 4 months to 60 years4,‡

Age-related data available for 243 of the 254 patients.

The Pyruvate Kinase Deficiency Natural History Study was funded by Agios Pharmaceuticals.

Symptom Burden

Diagnosed with PK deficiency in childhood; transfusion-dependent until splenectomized at age 8
Ages 8 to 49
5 RBC transfusions total
Nonsmoker; experiences decreased exercise tolerance, despite no changes to baseline hemoglobin, during her late 40s
Age 52
Receiving regular RBC transfusion (2 units every 8 weeks) to raise hemoglobin above 10.0 g/dL
Age 54
Requires 2 RBC units every 6 weeks
*Due to the variability of the disease, case profiles are not reflective of every patient.
In PK deficiency, hemoglobin levels may not correlate with disease severity4

Iron Overload

Transfusion dependence attributed to congenital anemia of unclear etiology
Age 8
Diagnosed with PK deficiency
Splenectomized; transfusion dependence resolved
Age 40

FACIT-F Score: 48 (score range, 0-52)

Ferritin 670 ng/mL (consensus cutoff, 500 ng/mL)

LIC: 8.9 mg/g dry weight (reference range, 0.17-1.8 mg/g dry weight)

Patient initiated on chelation therapy after being advised of the risks of iron overload

FACIT-F=Functional Assessment of Chronic Illness Therapy Fatigue.
*Due to the variability of the disease, case profiles are not reflective of every patient.

Diagnosed with nonspherocytic hemolytic anemia, later confirmed as PK deficiency
Given empirical iron supplementation
AGE 51
Symptoms of anemia minimal, and Hb averaged 9 g/dL; serum ferritin of 3700 μg/L
AGE 52
Hb level dropped to 6–7 g ⁄dL, and began requiring intermittent blood transfusions; refused chelation therapy
AGE 62
Diagnosed with diabetes mellitus and coincident hypotestosteronism; began chelation therapy (deferoxamine)
AGE 63
March: Heart failure secondary to iron overload precipitated an acute hospital admission; commenced on amiodarone and ACE inhibitors

April: Chelation therapy changed (due to suspected hearing impairment)

October: Became markedly confused with psychotic symptoms caused by acute hypothyroidism
  • Attributed to amiodarone and deferiprone, both of which can cause hypothyroidism; contribution of iron deposition in the thyroid gland uncertain
  • MRI confirmed extensive iron deposition in liver and pancreas; cardiac MRI not available
*Due to the variability of the disease, case profiles are not reflective of every patient.
Download our monitoring tool
Monitoring for iron overload is crucial to preventing complications and managing PK deficiency. Download our monitoring tool.6,7

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References: 1. Bianchi P, Fermo E, Glader B, et al. Addressing the diagnostic gaps in pyruvate kinase deficiency: consensus recommendations on the diagnosis of pyruvate kinase deficiency. Am J Hematol. 2019;94(1):149-161 [supplementary online material]. 2. Al-Samkari H, van Beers EJ, Kuo KHM, et al. The variable manifestations of disease in pyruvate kinase deficiency and their management [published online ahead of print March 12, 2020]. Haematologica. 2019;2019:240846. doi:10.3324/haematol.2019.240846. 3. Grace RF, Bianchi P, van Beers EJ, et al. Clinical spectrum of pyruvate kinase deficiency: data from Pyruvate Kinase Deficiency Natural History Study. Blood. 2018;131(20):2183-2192. 4. Zanella A, Fermo E, Bianchi P, Valentini G. Red cell pyruvate kinase deficiency: molecular and clinical aspects. Br J Haematol. 2005;130(1):11-25. 5. Marshall SR, Saunders PW, Hamilton PJ, Taylor PR. The dangers of iron overload in pyruvate kinase deficiency. Br J Haematol. 2003;120(6):1090-1091. 6. Grace RF, Layton DM, Barcellini W. How we manage patients with pyruvate kinase deficiency. Br J Haematol. 2019;184(5):721-734. 7. van Beers EJ, van Straaten S, Morton DH, et al. Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study. Haematologica. 2019;104(2):e51-e53.