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

PEPCK Mitochondrial Deficiency.

Extremely rare (four patients up to 2002).

Phosphoenolpyruvate carboxykinase (PEPCK) is encoded by two genes PCK1 (cytosolic form, located on chromosome 20) and PCK2 (mitochondrial form), and its expression is limited to the liver, kidney, and adipose tissue. Mode of inheritance is suspected as an autosomal recessive trait.

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.

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.

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 do not survive longer than 36 months.

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

Avoidance of hypoglycemia; monitoring of lactacidemia.

There are no specific implications.

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 B-1 (thiamine) caused by absorption problems and causing cardiovascular, CNS disturbances, including peripheral nerve manifestations. 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 disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, 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 in oxidative phosphorylation. Other clinical features include lesions of the optic nerve, heart, and breathing system. Symptoms during infancy include failure to thrive, tremors, and skin changes. It is suggested that it is inherited as an autosomal recessive trait.

Pyruvate Carboxylase Deficiency: A rare metabolic disorder characterized by severe lactic acidemia, CNS deterioration, vomiting, irritability, electrolyte imbalances, inactivity, hypotonia, abnormal eye movements, and seizures. The course of this disorder is progressive. It is inherited as an autosomal recessive trait.

Kerr DS, Wexler ID, Zinn AB: Disorders of pyruvate metabolism and the tricarboxylic acid cycle, in Fernandes J, Saudubray J-M, ...

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