Mitochondrial PEPCK deficiency

Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK) Deficiency is a rare metabolic disorder characterized by a deficiency in the mitochondrial form of the enzyme phosphoenolpyruvate carboxykinase (PEPCK). This enzyme plays a crucial role in gluconeogenesis, the metabolic pathway that allows the liver and kidneys to produce glucose from non-carbohydrate sources. The deficiency leads to various metabolic complications, primarily affecting the body's ability to maintain glucose homeostasis.

Symptoms and Clinical Presentation

Patients with mitochondrial PEPCK deficiency may present a range of symptoms, primarily due to hypoglycemia (low blood sugar levels), which is a direct consequence of impaired gluconeogenesis. Clinical manifestations can include:

• Fatigue
• Muscle weakness
• Hypoglycemia
• Lactic acidosis
• Growth retardation in children

The severity and onset of symptoms can vary significantly among individuals, with some cases detected in infancy and others in later childhood or early adulthood.

Genetics

Mitochondrial PEPCK deficiency is inherited in an Autosomal recessive manner. This means that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The gene responsible for encoding the mitochondrial form of PEPCK is located on chromosome 20q13.31. Mutations in this gene lead to reduced activity or complete absence of the enzyme, disrupting normal gluconeogenesis.

Diagnosis

Diagnosis of mitochondrial PEPCK deficiency involves a combination of clinical evaluation, biochemical tests, and genetic testing. Biochemical tests may reveal low blood sugar levels, elevated lactate levels, and other anomalies indicative of impaired gluconeogenesis. Genetic testing can confirm the diagnosis by identifying mutations in the gene responsible for the enzyme.

Treatment

There is no cure for mitochondrial PEPCK deficiency, and treatment focuses on managing symptoms and preventing hypoglycemia. Strategies may include:

• Frequent carbohydrate-rich meals to maintain blood sugar levels
• Cornstarch therapy to provide a slow-release form of glucose
• Dietary management to avoid fasting and manage lactic acidosis

In some cases, medications may be used to help control symptoms or complications arising from the disorder.

Prognosis

The prognosis for individuals with mitochondrial PEPCK deficiency varies depending on the severity of the enzyme deficiency and the effectiveness of the management strategies. Early diagnosis and intervention can improve the quality of life and reduce the risk of severe complications.

See Also

• Gluconeogenesis
• Metabolic disorder
• Hypoglycemia
• Lactic acidosis