What are the main differences in symptoms and severity between lactate dehydrogenase-A and lactate dehydrogenase-B deficiency?

Lactate dehydrogenase-A deficiency is the symptomatic form, characterized by exercise intolerance, muscle pain, cramps, and rhabdomyolysis (muscle breakdown) during strenuous activity. This can lead to myoglobinuria (dark urine) and potentially life-threatening kidney damage. In contrast, lactate dehydrogenase-B deficiency is typically asymptomatic, meaning individuals usually experience no symptoms or physical limitations and are often only diagnosed incidentally through routine blood tests showing reduced LDH activity.

What types of activities or exercises should someone with lactate dehydrogenase-A deficiency avoid, and what are the warning signs of a serious muscle breakdown?

Individuals with lactate dehydrogenase-A deficiency should generally avoid high-intensity, strenuous, or prolonged exercise that can trigger muscle breakdown (rhabdomyolysis). Activities that lead to significant muscle fatigue, pain, or cramping should be approached with caution

Lactate dehydrogenase deficiency

Lactate dehydrogenase deficiency is a rare genetic disorder that alters how the body breaks down sugar for energy, primarily affecting muscle cells. Depending on the genetic subtype, it can lead to severe exercise-induced muscle breakdown or remain completely asymptomatic.

Overview

Lactate dehydrogenase deficiency is a rare condition that affects how the body breaks down sugar to use as energy in cells, primarily muscle cells. In Japan, this condition affects approximately 1 in 1 million individuals; the prevalence of the condition in other countries is currently unknown.

There are two distinct types of this condition: lactate dehydrogenase-A deficiency (sometimes referred to as glycogen storage disease XI) and lactate dehydrogenase-B deficiency.

Symptoms

Lactate Dehydrogenase-A Deficiency

The severity of signs and symptoms among individuals with lactate dehydrogenase-A deficiency varies greatly. Common features include:

Fatigue, muscle pain, and cramps during exercise (exercise intolerance).
Breakdown of muscle tissue (rhabdomyolysis) triggered by high-intensity exercise or other strenuous activity.
The release of a protein called myoglobin from damaged muscle tissue, which is processed by the kidneys and released in the urine (myoglobinuria), causing the urine to appear red or brown.
Kidney damage from myoglobin, which in some cases can lead to life-threatening kidney failure.
Skin rashes.

Lactate Dehydrogenase-B Deficiency

People with lactate dehydrogenase-B deficiency typically do not have any signs or symptoms of the condition. They do not experience difficulty with physical activity and do not have any specific physical features related to the disorder. Affected individuals are usually discovered only when routine blood tests reveal reduced lactate dehydrogenase activity.

Causes & Genetic Factors

Mutations in the LDHA gene cause lactate dehydrogenase-A deficiency, and mutations in the LDHB gene cause lactate dehydrogenase-B deficiency. These genes provide instructions for making the lactate dehydrogenase-A and lactate dehydrogenase-B pieces (subunits) of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important for creating energy for cells. There are five different forms of this enzyme, each made up of four protein subunits in various combinations.

The version of lactate dehydrogenase made of four lactate dehydrogenase-A subunits is found primarily in skeletal muscles, which are used for movement. Skeletal muscles need large amounts of energy during high-intensity physical activity when the body's oxygen intake is not sufficient (anaerobic exercise). During anaerobic exercise, the lactate dehydrogenase enzyme is involved in breaking down sugar stored in the muscles (in the form of glycogen) to create additional energy. During the final stage of glycogen breakdown, lactate dehydrogenase converts a molecule called pyruvate to a similar molecule called lactate.

Mutations in the LDHA gene result in the production of an abnormal lactate dehydrogenase-A subunit that cannot attach (bind) to other subunits to form the enzyme. A lack of functional subunits reduces the amount of enzyme formed, mostly affecting skeletal muscles. As a result, glycogen is not broken down efficiently, leading to decreased energy in muscle cells. When muscle cells do not get sufficient energy during exercise or strenuous activity, the muscles become weak and muscle tissue can break down.

The version of lactate dehydrogenase made of four lactate dehydrogenase-B subunits is found primarily in cardiac muscle. In cardiac muscle, lactate dehydrogenase converts lactate to pyruvate, which can participate in other chemical reactions to create energy. LDHB gene mutations lead to the production of an abnormal lactate dehydrogenase-B subunit that cannot form the lactate dehydrogenase enzyme. Even though lactate dehydrogenase activity is decreased in the cardiac muscle of people with lactate dehydrogenase-B deficiency, they do not appear to have any signs or symptoms related to their condition. It is unclear why this type of enzyme deficiency does not cause any health problems.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

Deficiency of lactate dehydrogenase
Lactate dehydrogenase subunit deficiencies
LDH deficiency