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
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
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
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, ...