Summary about Disease
Malate dehydrogenase (MDH) deficiency is a rare genetic metabolic disorder that disrupts the citric acid cycle (Krebs cycle) responsible for cellular energy production. This deficiency primarily affects the nervous system and muscles due to reduced energy availability. MDH deficiency can manifest in varying degrees of severity.
Symptoms
Symptoms can vary widely depending on the severity of the deficiency. Common symptoms include:
Developmental delay
Muscle weakness (hypotonia)
Failure to thrive
Seizures
Lactic acidosis (build-up of lactic acid in the blood)
Encephalopathy (brain dysfunction)
Hypoglycemia
Causes
MDH deficiency is caused by mutations in the MDH2 gene. This gene provides instructions for making the malate dehydrogenase 2 enzyme, a critical component of the citric acid cycle. The mutations disrupt the enzyme's function, leading to impaired energy production. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no specific cure for MDH deficiency. Treatment focuses on managing symptoms and preventing complications. Medical interventions may include:
Dietary management: High-fat, low-carbohydrate (ketogenic) diet may provide an alternative energy source.
Supplementation: B vitamins, carnitine, and other supplements may be used to support metabolic function.
Seizure medications: Anticonvulsants to control seizures.
Lactic acidosis management: Sodium bicarbonate or other alkali agents.
Is Communicable
No, MDH deficiency is not communicable. It is a genetic disorder caused by gene mutations and cannot be transmitted from person to person.
Precautions
Precautions for individuals with MDH deficiency include:
Adhering to prescribed dietary and medication regimens.
Avoiding prolonged fasting or strenuous exercise, which can trigger metabolic crises.
Monitoring for signs of lactic acidosis or hypoglycemia.
Regular medical checkups to monitor disease progression and adjust treatment as needed.
Genetic counseling for families planning to have children.
How long does an outbreak last?
MDH deficiency isn't characterized by outbreaks. The symptoms are typically chronic, though their severity may fluctuate depending on factors like illness, stress, or dietary changes.
How is it diagnosed?
Diagnosis of MDH deficiency typically involves a combination of:
Clinical evaluation: Assessing symptoms and medical history.
Laboratory testing: Blood tests to measure lactic acid levels, glucose levels, and other metabolic markers.
Enzyme assay: Measuring MDH enzyme activity in blood or tissue samples.
Genetic testing: Analyzing the MDH2 gene to identify mutations.
Muscle biopsy: In some cases, a muscle biopsy may be performed to assess muscle tissue and enzyme activity.
Timeline of Symptoms
The onset and progression of symptoms can vary. Some individuals may show symptoms in infancy, while others may not develop symptoms until later in childhood or even adulthood. The timeline is highly variable and depends on the severity of the enzyme deficiency.
Important Considerations
Early diagnosis and intervention are crucial to managing MDH deficiency and improving outcomes.
Treatment is focused on symptomatic relief and minimizing metabolic stress.
Individuals with MDH deficiency require ongoing medical management by a team of specialists, including a geneticist, neurologist, and metabolic specialist.
Genetic counseling is recommended for families to understand the inheritance pattern and recurrence risk.