Introduction & Key Takeaways

Welcome! Dr. Houston here to discuss pyruvate kinase (PK) deficiency, a rare but important inherited metabolic disorder in cats that leads to hemolytic anemia and can impact quality of life and breeding decisions.

• 🧬 Caused by PKLR gene mutations—autosomal recessive in cats.
• ✅ Predisposed breeds: Abyssinian, Somali, plus others like Bengals, Maine Coons, domestic shorthairs.
• ⚠️ Symptoms range from mild lethargy to severe anemia, jaundice, and organ enlargement.
• 💉 Diagnosis via CBC, reticulocyte count, enzyme assay, and genetic testing.
• 🩺 No cure; management includes supportive care, transfusions, sometimes splenectomy.
• 🔄 Breeding guidance critical: avoid mating carriers to prevent affected offspring.
• 🔬 Emerging therapies? In humans, the drug *mitapivat* shows promise—but not yet used in cats.

1. What Is PK Deficiency?

PK deficiency is a genetic enzyme defect that impairs RBC energy production. Without functional pyruvate kinase, red blood cells can’t produce enough ATP, leading to early cell death (hemolysis) :contentReference[oaicite:3]{index=3}.

While humans may have many mutations, cats typically carry a specific intronic SNP in the PKLR gene—leading to faulty splicing and truncated protein :contentReference[oaicite:4]{index=4}.

The result? RBCs live shorter lives and the cat develops hemolytic anemia—often chronic or intermittent :contentReference[oaicite:5]{index=5}.

2. Who’s Affected?

PK deficiency is autosomal recessive—an affected cat inherits mutated genes from both parents, while carriers (one copy) remain healthy :contentReference[oaicite:6]{index=6}.

Breeds commonly impacted include:

• Abyssinian, Somali
• Domestic shorthair/longhair
• Bengal, Maine Coon, Norwegian Forest, Siberian, Egyptian Mau, LaPerm, Savannah, Singapura, Australian Mist, Toyger :contentReference[oaicite:7]{index=7}.

Onset can be as young as a few months but most often by 3–5 years old :contentReference[oaicite:8]{index=8}.

3. Signs & Symptoms

Key clinical signs include:

• Lethargy, weakness, exercise intolerance 💤 :contentReference[oaicite:9]{index=9}
• Pale gums, jaundice (rarely), poor coat, weight loss :contentReference[oaicite:10]{index=10}
• Enlarged spleen and liver (hepatosplenomegaly) :contentReference[oaicite:11]{index=11}
• Tachycardia, increased respiratory rate :contentReference[oaicite:12]{index=12}
• Intermittent hemolytic episodes—fatigue, fever, dark urine :contentReference[oaicite:13]{index=13}
• Occasional diarrhea, pica behavior :contentReference[oaicite:14]{index=14}

Severity varies widely—some remain stable with mild symptoms, others need lifesaving care :contentReference[oaicite:15]{index=15}.

4. Diagnosis

Diagnostic steps:

1. History & physical exam: breed, age, signs, breed history.
2. CBC & reticulocyte count: anemia, elevated immature RBCs, reticulocytosis :contentReference[oaicite:16]{index=16}.
3. Biochemistry: increased bilirubin, liver enzymes; sometimes hyperglobulinemia :contentReference[oaicite:17]{index=17}.
4. Enzyme assay: measures RBC pyruvate kinase activity.
5. Genetic testing: cheek swab or blood sample confirms mutation/carrier status :contentReference[oaicite:18]{index=18}.
6. Exclude other causes: infectious (FeLV, Mycoplasma), iron-deficiency, immune-mediated anemia :contentReference[oaicite:19]{index=19}.

5. Treatment & Management

There is no cure—care is symptomatic and supportive :contentReference[oaicite:20]{index=20}.

• Supportive care: quality nutrition, hydration, rest, stress reduction :contentReference[oaicite:21]{index=21}.
• Blood transfusions: for severe anemia or hemolytic crisis :contentReference[oaicite:22]{index=22}.
• Splenectomy: occasionally used to reduce RBC destruction in spleen :contentReference[oaicite:23]{index=23}.
• Medications: iron, folate, enteral antioxidants if needed—and carefully manage infections.
• Emerging drugs: *Mitapivat* approved in humans (2022) as a PK activator; yet not currently used in cats, but promising for the future :contentReference[oaicite:24]{index=24}.
• Regular vet checks: CBC monitoring, organ health, transfusion planning.

6. Prognosis

Outcome depends on severity:

• 🟢 Mild cases → good quality of life with minimal treatment and monitoring.
• ⚠️ Severe cases → dependent on transfusions, possible organ complications, risk of shortened lifespan :contentReference[oaicite:25]{index=25}.
• 💔 Stressors (like infection) can trigger life-threatening hemolytic crises :contentReference[oaicite:26]{index=26}.