Summary about Disease
Dihydrolipoamide dehydrogenase (DLDH) deficiency, also known as E3 deficiency, is a rare inherited metabolic disorder that disrupts the body's ability to process certain amino acids and carbohydrates. This deficiency affects several important enzyme complexes involved in energy production within the mitochondria. These complexes include the pyruvate dehydrogenase complex (PDH), alpha-ketoglutarate dehydrogenase complex (α-KGDH), branched-chain ketoacid dehydrogenase complex (BCKDH), and the glycine cleavage system. A defect in the DLDH enzyme disrupts the function of all these complexes, leading to a build-up of toxic substances in the blood and tissues.
Symptoms
Symptoms of DLDH deficiency vary significantly in severity and age of onset. They can include:
Early onset (infancy): Severe lactic acidosis, hypotonia (floppy muscle tone), failure to thrive, seizures, developmental delay, and liver problems. May be fatal in early infancy.
Later onset (childhood or adulthood): Milder lactic acidosis, ataxia (lack of coordination), peripheral neuropathy, muscle weakness, exercise intolerance, and cognitive impairment. Episodes may be triggered by illness or stress.
Intermittent symptoms: Some individuals experience symptoms only during periods of metabolic stress, such as illness or fasting.
Causes
DLDH deficiency is caused by mutations in the DLD gene. This gene provides instructions for making the dihydrolipoamide dehydrogenase (E3) enzyme. The deficiency is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected. Individuals who carry only one copy of the mutated gene are carriers and do not typically exhibit symptoms.
Medicine Used
4. Medicine used There is no specific cure for DLDH deficiency. Treatment focuses on managing symptoms and preventing metabolic crises. Common management strategies include:
Dietary modifications: A low-carbohydrate, high-fat (ketogenic) diet may be recommended to reduce the reliance on affected metabolic pathways.
Supplementation:
Thiamine (vitamin B1) and L-carnitine may be prescribed.
Riboflavin (Vitamin B2) is often prescribed to improve enzyme function.
Emergency treatment: During metabolic crises, intravenous fluids, glucose, and bicarbonate may be necessary to correct dehydration, hypoglycemia, and acidosis.
Medications: Other medications may be used to manage specific symptoms, such as seizures.
Is Communicable
DLDH deficiency is not communicable. It is a genetic disorder caused by a mutation in the DLD gene and is inherited from parents to their children. It cannot be spread through contact with an affected individual.
Precautions
Individuals with DLDH deficiency, and their families, should take the following precautions:
Strict adherence to dietary guidelines: Following the prescribed diet is crucial for managing the condition.
Avoidance of prolonged fasting: Fasting can trigger metabolic crises. Regular meals and snacks are essential.
Prompt treatment of illness: Even minor illnesses can lead to metabolic decompensation. Seek medical attention promptly.
Awareness of metabolic triggers: Identify and avoid potential triggers, such as stress, infection, or certain medications.
Emergency plan: Have a written emergency plan outlining steps to take during a metabolic crisis. This should be shared with caregivers and healthcare providers.
Genetic counseling: Family members should consider genetic counseling to assess their risk of being carriers and the risk of having affected children.
How long does an outbreak last?
The duration of a metabolic crisis or "outbreak" varies depending on the severity of the condition, the promptness of treatment, and the individual's response to therapy. A mild episode might resolve within a few hours with appropriate management, while a severe episode could last for days or even weeks, potentially requiring hospitalization.
How is it diagnosed?
Diagnosis of DLDH deficiency typically involves a combination of the following:
Clinical evaluation: Assessment of symptoms, medical history, and family history.
Laboratory tests:
Blood tests to measure lactic acid, ammonia, and amino acid levels.
Urine tests to detect organic acids.
Fibroblast enzyme assay: Measuring DLDH enzyme activity in cultured skin cells.
Genetic testing: Sequencing of the DLD gene to identify mutations.
Newborn Screening: While not universally included, some newborn screening programs can detect DLDH deficiency.
Timeline of Symptoms
The timeline of symptoms can vary significantly:
Neonatal/Infancy: Severe lactic acidosis, hypotonia, feeding difficulties, respiratory distress, liver dysfunction, neurological problems (seizures, coma), and potentially death within weeks or months.
Childhood: Delayed development, ataxia, muscle weakness, fatigue, episodes of vomiting and lethargy during illness.
Adulthood: Exercise intolerance, peripheral neuropathy, cognitive impairment, episodes of lactic acidosis triggered by stress or illness. Some individuals may have a milder presentation with subtle symptoms.
Important Considerations
Variable Expression: The severity of DLDH deficiency can vary widely, even among individuals with the same genetic mutation.
Early Diagnosis: Early diagnosis and treatment are crucial to improve outcomes and prevent irreversible damage.
Long-Term Management: DLDH deficiency requires lifelong management, including dietary modifications, supplementation, and monitoring.
Multidisciplinary Care: Management often involves a team of specialists, including a metabolic geneticist, nutritionist, neurologist, and other healthcare professionals.
Research: Ongoing research is focused on developing new therapies and improving the understanding of DLDH deficiency.