OF FATTY ACID METABOLISM
coma due to a disorder of fatty acid oxidation may occur with any of the
following conditions: (1) deficiency of short-chain, medium-chain, or
long-chain acyl-CoA dehydrogenases; (2)
multiple acyl-CoA dehydrogenase deficiency (glutaric acidemia II) More
(3) hydroxymethylglutaryl-CoA dehydrogenase deficiency; and (4) carnitine
The characteristic features of fatty acid oxidation disorders are mild
metabolic acidosis, nonketotic hypoglycemia, low or normal total carnitine
blood levels, dicarboxylic aciduria.
Mild hyperammonemia and slight elevation of liver transaminases may also
be present with fatty acid oxidase disorders. Final diagnosis is established
by demonstration of the enzymatic defect in leukocytes and fibroblasts.
Treatment consists of stopping fat intake, correcting hypoglycemia with
glucose, and providing oral carnitine at 100 mg/kg per day. Riboflavin
at 50 to 750 mg daily is recommended. Fasting should be avoided.
OF CARBOHYDRATE METABOLISM
due to an inborn error in the metabolism of carbohydrates occurs in fructose-1-6
diphosphate deficiency and in fructose-1-phosphate aldolase deficiency
(hereditary fructose intolerance). Fructose-1-6 diphosphate deficiency
produces accumulation of lactic and pyruvic acids, increased ketosis,
and hypoglycemia. Treatment consists of continuous glucose supplementation
to avoid gluconeogenesis. Hereditary fructose intolerance presents with
vomiting after the introduction of fruit juice or table sugar to the neonatal
diet. Continuous vomiting leads to coma. Carbohydrate abnormalities are
diagnosed by finding reduced enzyme activity in the liver. Treatment consists
of eliminating fructose from the diet and correcting hypoglycemia.
syndrome is produced by mutations in methyl-CpG-binding protein 2 (MECP2),
located at the Xq28. Rett syndrome produce neonatal encephalopathy in
boys. The encephalopathy is characterized by seizures, cortical myoclonus,
hypotonia and central apnea. Rett syndromes in male neonates may occur
in families with females siblings affected by Rett syndrome or not.
The study of choice is DNA for Rett syndrome. Genetic evaluation for
parents is warranted.
OF A NEONATE WITH A SUSPECTED METABOLIC DISORDER
help establish a prompt diagnosis of a metabolic disorder in a neonate
with a suspected metabolic disorder, group them according to the results
of the most readily available blood test: blood pH, glucose, lactate and
ammonia, and urine ketones. Neonates with ketoacidosis and hypoglycemia
are likely to have a metabolic error that involves the leucine pathway,
propionic or methylmalonic acidemias, or a disorder of carbohydrate metabolism.
Neonates with hyperammonemia and respiratory alkalosis usually have a
urea cycle defect. Neonates with low urinary ketones and hypoglycemia
usually have a disorder of mitochondrial fatty acid oxidation. Neonates
with lactic acidosis are likely to have pyruvate dehydrogenase deficiency,
pyruvate carboxylase deficiency, or a respiratory chain enzyme defect,
but other disorders are frequently occurs in this group. The evaluation
of neonates with lactic acidosis is complicated since elevated lactic
acids frequently occur in a large number of disorders.
errors of metabolism that present with lactic acidosis in neonates can
be grouped according to the results of the urine organic acids. Lactic
acidosis and organic aciduria occur with fatty acid oxidative defects,
biotinidase and multiple carboxylase deficiencies and in organic acidemias.
Lactic acidosis without organic aciduria occurs in pyruvate dehydrogenase,
glucogenic enzymes, pyruvate carboxylase, and respiratory chain defects.
errors of metabolism that present with lactic acidosis without organic
acidemia can be further grouped according to the lactate/pyruvate ratio
and the pyruvate concentration. The normal lactate (0.8 to 2.2 mmol/L)
to pyruvate (0.04 to 0.01 mmol/L) blood concentration ratio is less than
25 (lactate 25: pyruvate 1). The lactate/pyruvate ratio depends on the
state of tissue oxygenation (lactate = pyruvate multiplied by the state
of tissue oxygenation [x]). The state of tissue oxygenation x depends
on the amount of NADH2 and NAD in the cytosol (NADH2/NAD).
So a metabolic disorder associated with lactic acidosis and a high number
in x will have a high serum lactate level despite low serum pyruvate levels
(increased lactate/pyruvate ratio [lactate >35: pyruvate 1]); whereas
diseases with lactic acidosis and a lower x will have a high serum lactate
level at the expense of a high pyruvate level (low lactate/pyruvate level
[lactate <25: pyruvate 1]).