Phosphofructokinase (PFK) deficiency

roblib — Mon, 22 Mar 2010 17:50:09 +0000

What is ... ?:

The enzyme PFK is important in energy metabolism in red blood cells and in skeletal muscle during intense exercise. PFK deficiency is an inherited disorder that causes premature breakdown (hemolysis) of red blood cells, and a reduced tolerance for exercise. Affected dogs have chronic mild anemia with intermittent bouts of acute hemolysis, often associated with intense exercise, overheating or prolonged barking.

How is ... inherited?:

This is an autosomal recessive trait which means both parents of an affected dog are carriers of the disorder. Carriers have about one half normal enzyme activity in red blood cells and muscle tissue, and are clinically unaffected.

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Affected dogs have a persistent mild anemia (low levels of red blood cells) for which they are generally able to compensate. Intermittently they will have acute episodes of red blood cell breakdown (hemolysis), when they become lethargic and weak. This is usually associated with intense exercise or excessive barking or panting. Their mucous membranes (eg. gums) are pale or jaundiced and they usually run a high fever. You may notice the urine is brown due to the excretion of blood breakdown products. At these times your dog will require veterinary attention.

Dogs with this condition can have a normal life span. Management of this condition requires avoidance of stress, strenuous exercise, overheating and over excitement.

How is ... diagnosed?:

Based on clinical examination and blood tests, your veterinarian will diagnose hemolytic anemia (low levels of red blood cells due to increased breakdown) in your dog. Further tests will be required to diagnose this specific condition.

How is ... treated?:

There is no specific treatment for this disorder, other than supportive care during an episode of bleeding (which may require a blood transfusion). Carrier and affected dogs should be removed from the breeding population.

The condition can be well-managed, and your veterinarian will discuss this with you. You will need to be alert for signs associated with increased intravascular hemolysis (red cell breakdown), such as weakness, lethargy, pale or jaundiced mucous membranes, or brownish urine. It is also important to avoid stressful situations, strenuous exercise, excitement that will cause a great deal of barking, and high environmental temperatures.

For the veterinarian:

CLINICAL: persistent compensated hemolytic anemia (PCV at or near normal) with intermittent hyperventilation-induced hemolytic crises with (usually mild) exertional myopathy, poor exercise tolerance; during hemolytic crisis, signs may include lethargy, weakness, hepatosplenomegaly, muscle wasting, pale or icteric mucous membranes, pyrexia (to 41 degrees Celsius).

LABORATORY: A specific genetic test can identify carriers and affected animals at any age (see reference below). Affected and carrier dogs can also be identified based on PFK activity in blood samples. Check with your clinical pathology lab for requirements for sample submission.

Breeding advice:

Because this is an autosomal recessive trait, both parents of affected dogs carry the defective gene. Neither affected (homozygous) or carrier dogs (heterozygous) should be used for breeding. There is a DNA test that can identify carrier dogs at any age (see reference below). Many affected and carrier dogs have already been removed from the breeding population.

Resources:

Harvey, J.W. 1995. Congenital hemolytic anemias and methemoglobinemias. ACVIM-Proceedings of the 13th Annual Veterinary Medical Forum: 37-40.

Henderson A. Anemia, Hemolytic. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:64-66.

Sargan DR. Phosphofructokinase deficiency. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.

Genetic testing (English and French) Labgenvet: www.labgenvet.ca

www.vetgen.com - information on genetic testing available

Pyruvate kinase (PK) deficiency

roblib — Mon, 29 Mar 2010 14:26:31 +0000

What is ... ?:

Pyruvate kinase is a key enzyme in energy metabolism in red blood cells. This inherited disorder causes a deficiency in this enzyme which results in a marked shortening of the life span of red blood cells, and therefore a severe hemolytic anemia - low red blood cell numbers due to cell breakdown.

How is ... inherited?:

What breeds are affected by ... ?:

What does ... mean to your dog & you?:

Dogs with PK deficiency usually show signs by 4 months to 1 year of age. Because of the severe anemia (low levels of red blood cells), affected dogs are slow to grow, and show a mild weakness and a low tolerance for exercise. Unfortunately these dogs also gradually develop changes in their bones, specifically replacement of the bone marrow with fibrous tissue, and hardening or abnormal density of bone (called myelofibrosis and osteosclerosis). Dogs with pyruvate kinase deficiency usually die before 4 years of age, due to bone marrow failure and/or liver disease.

How is ... diagnosed?:

Signs of anemia include pale mucous membranes (your dog's gums for example), an increased heart rate and a reduced tolerance for exercise. Your veterinarian will do blood tests to determine the cause of the anemia which in this disorder is due to increased red blood cell breakdown. Further tests will be required to diagnose this specific condition as the cause of the hemolytic anemia.

How is ... treated?:

There is no specific treatment for this disorder, other than supportive care as necessary.

For the veterinarian:

HEMATOLOGY: persistent, severe (PCV 12 to 26%), highly regenerative anemia which becomes less responsive as the dog ages.
DIAGNOSIS: Erythrocytes from affected dogs completely lack the normal R-type PK isoenzyme, but they do have an abnormal M-type PK isoenzyme. Thus special laboratory tests are required to diagnose a PK deficient dog, rather than simply measuring total PK activity. Carrier dogs, with half normal activity, can also be identified. Check with your clinical pathology lab for requirements for sample submission. A DNA diagnostic test has been developed for Basenjis and West Highland white terriers which can identify carriers and affected animals at any age (see reference below).
OTHER SIGNS: hepatosplenomegaly, progressive myelofibrosis and osteosclerosis, +/- terminal liver disease with hemochromatosis and cirrhosis.

Breeding advice:

Resources:

Harvey, J.W. 1995. Congenital hemolytic anemias and methemoglobinemias. ACVIM-Proceedings of the 13th Annual Veterinary Medical Forum: 37-40.
Henderson A. Anemia, Hemolytic. In: Côté E, ed. Clinical Veterinary Advisor Dogs and Cats. Missouri: Mosby Elsevier, 2007:64-66.
Sargan DR. Pyruvate kinase deficiency. In IDID - Inherited diseases in dogs:web-based information for canine inherited disease genetics.
vetGen - information on genetic testing available (Basenjis and West Highland white terriers)

Hemolytic anemia

Phosphofructokinase (PFK) deficiency

Pyruvate kinase (PK) deficiency