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ERRORS OF PROTEIN METABOLISM THAT DO NOT INVOLVE THE LEUCINE PATHWAY

Errors of protein metabolism that do not involve the leucine pathway include glycine encephalopathy, propionic and methylmalonic acidemias, sulfite oxidase deficiency, and pyruvate metabolism disorders. Propionic and methylmalonic acidemias are also known as organic acidemias.

Glycine encephalopathy
Glycine encephalopathy is diagnosed by finding elevated glycine in the blood, urine, or cerebrospinal fluid in the absence of: (1) ketosis, (2) abnormal serum amino profile, and (3) abnormal urine organic acid profile. The cerebrospinal fluid to plasma glycine ratio is above 0.09 (in normal circumstances and in secondary hyperglycemia it is below 0.04). The diagnosis is only excluded by finding a normal cerebrospinal fluid glycine level. Three findings may suggest glycine encephalopathy: (1) hiccups; (2) an EEG with a burst suppression pattern; and (3) a brain imaging study with white matter hypodensity and partial or total absence of the corpus callosum. There is no satisfactory pathophysiologic treatment. Seizures should be treated with diazepam. The prognosis of glycine encephalopathy is very poor in most cases, although a transient variety with good prognosis also occurs. Elevated levels of glycine are also found in inborn errors of metabolism that have an increase in coenzyme-A derivatives including tiglyl-CoA, propionyl-CoA, methylmalonyl-CoA, and isovaleryl-CoA. The disorders produced by these enzyme deficiencies are denominated secondary hyperglycinemia.

Propionic and methylmalonic acidemias
Coma due to propionic and methylmalonic acidemias lack specific clinical characteristics. These disorders should be considered in neonates with urine pH below 5.5 and if the calculated anion gap (Na - [Cl + HCO3]) is in excess of 20 mmol/L.
The metabolic profile of propionic acidemia consists of the accumulation of propionyl-CoAanditsmetabolites in urine: methylcitrate and 3-hydroxypropionate. In addition, the metabolic profile reflects dysfunction of the citric acid cycle (lactic acidosis), pyruvate dehydrogenase complex (lactic acidosis), N-acetylglutamate synthetase (hyperammonemia), and glycine cleavage (hyperglycinemia).

 

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Volpe, 1995 Volpe, 1990 Tada, 1990 Ozand, 1991a Ozand, 1991b Burlina, 1999