Lactate dehydrogenase (LDH) deficiency is a rare genetic condition impacting the body’s ability to break down sugars for energy, especially within muscle cells. This disorder occurs when the body does not produce enough of the lactate dehydrogenase enzyme.
The Role of Lactate Dehydrogenase (LDH)
Lactate dehydrogenase (LDH) is an enzyme found in nearly all body tissues, including muscles, red blood cells, heart, liver, and kidneys. Its primary function involves a reversible conversion between lactate and pyruvate, which are molecules central to energy production. This process is particularly important during anaerobic conditions, where oxygen levels are low, such as during strenuous physical activity.
During intense exercise when oxygen is scarce, LDH converts pyruvate into lactate. This regenerates NAD+, necessary for glycolysis, which produces ATP, the body’s main energy currency. When oxygen becomes available, LDH can convert lactate back to pyruvate for energy generation or transport to the liver for glucose production through the Cori cycle.
Recognizing LDH Deficiency: Symptoms and Types
Symptoms of LDH deficiency typically become apparent in adulthood and usually do not worsen over time. The specific symptoms experienced depend on the type of LDH deficiency present. There are two primary types: lactate dehydrogenase-A deficiency (LDH-A deficiency) and lactate dehydrogenase-B deficiency (LDH-B deficiency).
Individuals with LDH-A deficiency often experience fatigue, muscle pain, and cramps, particularly during physical exertion. This condition can lead to exercise intolerance, making sustained activity difficult. In some cases, high-intensity exercise can cause rhabdomyolysis, a breakdown of muscle tissue that releases myoglobin into the bloodstream. Myoglobin can then be processed by the kidneys and excreted in the urine, giving it a red or brown color, and potentially leading to kidney damage or even life-threatening kidney failure. Some individuals with LDH-A deficiency may also develop skin rashes.
In contrast, people with LDH-B deficiency typically do not exhibit any noticeable signs or symptoms. This type of deficiency is often discovered incidentally during routine blood tests that reveal reduced LDH activity.
Causes, Diagnosis, and Management of LDH Deficiency
Lactate dehydrogenase deficiency is a genetic disorder inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene typically do not show symptoms themselves but can pass the gene to their children.
The condition is caused by mutations in either the LDHA gene, which leads to LDH-A deficiency, or the LDHB gene, which results in LDH-B deficiency. These genes provide instructions for creating the LDH-A and LDH-B subunits that combine to form the complete lactate dehydrogenase enzyme. A mutation in either gene results in an abnormal subunit that cannot properly form the enzyme, leading to reduced enzyme activity.
Diagnosis of LDH deficiency typically involves a combination of methods. Blood tests are often used to measure LDH levels, and they may also reveal elevated levels of other metabolites such as creatine phosphokinase, lactate, and pyruvate, which are often increased when this condition is present. Genetic testing is commonly performed to confirm the specific gene mutation, particularly if a family history of the condition exists. In certain situations, a muscle biopsy might be considered to check for abnormalities in muscle tissue.
There is currently no cure for LDH deficiency, as it is a genetic condition. Management focuses on supportive care and addressing symptoms as they arise. This can include avoiding strenuous exercise to prevent muscle breakdown and pain, and staying well-hydrated. Physical therapy may be beneficial for managing muscle cramps and pain, and for gradually improving exercise tolerance. Genetic counseling can also provide valuable information about inheritance patterns and assist families in making informed decisions about managing the condition.