PROTEIN METABOLISM THAT DO NOT INVOLVE THE LEUCINE PATHWAY
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.
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
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.
and methylmalonic acidemias
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
metabolic profile of propionic acidemia consists of the accumulation of
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).