Amino acid composition of body fluids and nervous tissue of normal calves and those affected with neuraxial oedema

High performance liquid chromatography was used in amino acid analyses of body fluids and nervous tissues from newborn Poll Hereford calves. After separation on a lithium cation exchange column, primary amino acids were derivatised with ortho-phthalaldehyde and detected fluorimetrically. Normal values are presented for plasma, cerebrospinal fluid, dorsal spinal cord, ventral spinal cord, medulla oblongata, pons, white matter of the cerebellum, grey matter of the cerebellum, frontal cortex, temporal cortex, occipital cortex, amygdala, thalamus, putamen, caudate nucleus and substantia nigra. Normal ratios of branched chain amino acids to alanine are presented for urine, formalin-fixed cerebrum and fixative. Amino acid analyses of tissues and body fluids from calves affected with neuraxial oedema has shown that this "disease" consists of two separate neurological conditions Inherited Congenital Myoclonus and Maple Syrup Urine Disease. Both conditions are inherited in an autosomal recessive manner. Calves affected with Inherited Congenital Myoclonus are bright and alert, but unable to stand from birth. If fed, they are viable for an indefinite period. The clinical signs are stimulus-responsive and spontaneous myoclonic spasms. There are no lesions in the central nervous system, but most Inherited Congenital Myoclonus calves have traumatic hip joint lesions, the result of myoclonic spasms in utero. Concentrations of free amino acids, including known neurotransmitters, in tissues and fluids were not consistently different from normal calves. Normal levels of minerals and enzymes were also found in plasma and/or cerebrospinal fluid. The biochemical lesion in Inherited Congenital Myoclonus has been shown to be a glycine receptor site abnormality in the spinal cord, with no effect on the free glycine pool. Calves affected with Maple Syrup Urine Disease are apparently normal at birth, but develop clinical signs of dullness and opisthotonus 1-3 days after birth. Death occurs within the first week. Vacuolation of the white matter of the central nervous system gives the oedematous appearance which originally initiated the term, "neuraxial oedema". Elevated levels of the three branched chain amino acids valine, isoleucine and leucine are evident in all samples analysed. The branched chain amino acids have also been shown to be elevated at birth. Ratios of valine, isoleucine and leucine to alanine are elevated in urine and fixed nervous tissue. A deficiency in the activity of the enzyme, branched chain keto acid decarboxylase has been demonstrated in fibroblast cultures from these calves. As a result of this block, the corresponding branched chain keto acids, ketoisovaleric, ketomethylvaleric and ketoisocaproic, are also elevated. This is the first reported aminoacidopathy in ruminants and the only known model of Maple Syrup Urine Disease in man.