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At a glance

Congenital metabolic disease leading to defect of gluconeogenesis and severe acidemia. Other clinical features include hypotonia, hypoglycemia, hepatomegaly, and growth delay.

Synonyms

PEPCK Mitochondrial Deficiency; PEPCK Cytosolic Deficiency; PCK1 Deficiency.

Incidence

Extremely rare, reported in fewer than 20 patients.

Genetic inheritance

Autosomal recessive.

Pathophysiology

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is caused by homozygous PCK1 gene mutation. PEPCK is encoded by two genes PCK1 (cytosolic form, 20q13.31) and PCK2 (mitochondrial form, 14q11), and its expression is limited to the liver, kidney, and adipose tissue. PEPCK is the rate-controlling enzyme of gluconeogenesis in the liver and kidney; it converts pyruvate, lactate, alanine, and intermediates of the tricarboxylic acid cycle to glucose.

Diagnosis

Hypoglycemia associated with lactic acidosis; measurement of PEPCK activity on fresh liver biopsy. Caution: PEPCK activity is physiologically depressed in hyperinsulinar states and might be a secondary phenomenon in case of respiratory chain dysfunction.

Clinical aspects

Major manifestation is fasting hypoglycemia with lactic acidosis; multisystem involvement may be present with neuromuscular deficits, hepatic damage, renal tubular acidosis. Hepatomegaly with lethargy and hypotonia are common. Patients are not reported to survive into adulthood.

Precautions before anesthesia

A glucose-containing IV solution should be started at the beginning of the preoperative fasting period.

Anesthetic considerations

Avoidance of hypoglycemia; monitoring of lactacidemia.

Pharmacological implications

There are no specific implications.

Other conditions to be considered

  • Korsakoff Syndrome (Wernicke-Korsakoff Syndrome; Transketolase Defect Syndrome; Alcohol-Induced Encephalopathy Syndrome): Characterized by acute encephalopathy followed by chronic impairment of short-term memory. Early treatment with high doses of thiamine stabilizes the disease, yet thiamine deficiency is not sufficient to cause the syndrome. It is a deficiency of vitamin B1 (thiamine) caused by absorption problems and causing cardiovascular, central nervous system (CNS) disturbances, including peripheral nerve manifestations. There appears to be an inborn error of metabolism that is clinically important only when the diet is inadequate in thiamine indicating that this syndrome is a recessive disorder, presumably autosomal recessive. It is common in the Orient where excessive milling of rice reduces its thiamine content. Beriberi is caused by lack of dietary thiamine and its symptoms include myocardial failure, reversible by thiamine treatment.

  • Leigh Syndrome: An early-onset progressive neurodegenerative mitochondrial cytopathy with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system (CNS), including the brain stem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the CNS are involved. The most common underlying cause is a defect ...

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