Lipoamide dehydrogenase was measued in cultivated skin fibroblasts from twelve patients with Friedreich's ataxia and nine normal controls. No difference in specific activity, subcellular distribution and Vmax or Km was observed between patients and controls.

The uptake of 14C-laurine was studied in the platelets of 20 ataxic patients and 20 age-matched normal control subjects. No significant differences were found in uptake or kinetics of taurine between the two groups of subjects. If a transport defect in taurine exists in Friedreich's ataxia, it is not present in all tissues. Preliminary indication was obtained in favor of heterogenity of the uptake pattern between ataxic individuals.

In a previous study we reported low values of taurine and aspartic acid in the CSF of patients with Friedreich's ataxia, when the results were compared to the literature. Further studies have revealed that tinforetold difficulties with the advertised methodology of sequential multi-sample amino acid analysis were responsible for low values in the determination of these two amino acids in the small volumes necessary for CSF. A corrected method is presented. With the latter method the differences disappear for CSF taurine and aspartic acid, but they remain valid for the previously reported blood and urine values in Friedreich's ataxia. GABA levels are also normal in Friedreich's ataxia CSF.

A single intraperitoneal injection of 3-acetyl pyridine produces, within 24 hours of administration, signs of cerebellar ataxia and damage to the medulla oblongata and to the climbing fibers of the cerebellum. These changes are accompanied by changes in the concentration of certain amino acids in the appropriate areas. Glutamic acid is decreased in cerebellum, medulla, cortex, striatum, hippocampus, retina and olfactory bulbs, while taurine is specifically decreased in the cerebellum and medulla oblongata and aspartic acid in the retina. The concentrations of GABA and glycine are not modified in any of the areas studied. Glutamine is generally increased in concentration in areas of cell damage.

Rats rendered diabetic by alloxan monohydrate were studied to investigate the effect of increased blood glucose upon the concentration of various putative neurotransmitter amino acids in the cerebellum. No modification was found in the concentrations of glutamate, gamma aminobutyric acid (GABA), glutamine, glycine or taurine, but there was a significant decrease in the cerebellar concentration of aspartate in the diabetic animals. This raises the question of the specificity of the aspartic acid defect found in some form of ataxia.

The intraperitoneal (IP) or intraventricular (IVT) administration of small amounts of taurine did not modify pentobarbital-induced sleep or pituitary hormone release. However, the drastic increment in plasma GH values induced by morphine administration was completely blocked by the IVT injection of the amino acid. Whether taurine plays a physiological role in the control ofGH secretion is highly speculative.

In a detailed investigation of nucleotide synthesis, intercom'ersion and degradation, no difference was found between subjects with Friedreich's Ataxia and normal controls. It appears improbable that this disorder is related to a primary defect in purine metabolism.

A systematic study of plasma lipids and lipoproteins was carried out in II cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using II healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.

This review evaluates the theoretical background and experimental data behind a new development: the replacement therapy of deficient central cholinergic systems with the dietary precursors choline or lecithin. Cholinergic deficiency states are possibly present in five neurological entities: Huntington's chorea, Tardive Dyskinesia, Gilles de la Tourette's disease, Friedreich's ataxia and presenile dementia. Preliminary data from various laboratories, including our own, in each of these disorders indicate that some clinical improvement can occasionally be seen, and that this approach deserves further investigation.

In the present overview an attempt is made to summarize the investigations carried out during the first part of Phase Two of the Quebec Cooperative Study of Friedreich's Ataxia. These investigations delineated the relative importance of various biochemical leads uncovered during the preliminary survey. It is possible to indicate some findings that may be primary and which should be pursued in subsequent investigations. Among these, the observation of an abnormal composition of high density lipoproteins in Friedreich's Ataxia appears to be the most important.