Glutaric acidemia (type I) is another rare metabolic disorder, in which progressive choreoathetosis and dystonia are combined with intermittent acidemia. In some cases, ataxia of movement and a variable degree of mental retardation are also present. Glutaric acid is present in the urine, as are its metabolites 3-hydroxyglutarate and glutamate. The basic defect is in glutaryl CoA dehydrogenase, which has been found in leukocytes, hepatocytes, and fibroblasts. Neuropathologically, there is loss of neurons in the caudate, putamen, and pallidum, with gliosis.
A spongy change is said to affect the white matter.
Infants with glutaric acidemia are often subject to sudden episodes of acidosis, coma, and flaccidity. There are signal changes on MRI, corresponding to the acute necrosis of nerve cells in the basal ganglia. These crises can be prevented and the infants can develop normally if the diagnosis is made before the development of neurologic signs, for example, in the sibling of an older affected child, and treatment is undertaken with a diet low in protein, particularly in tryptophan and lysine (Cho et al).
THE LEUKODYSTROPHIES: SYNDROMES
OF BILATERAL HEMIPLEGIA, BLINDNESS,
Categorized here are late life manifestations of familial leukodystrophies. Of the several varieties of late-onset leukodystrophy, some are of unquestionable metabolic origin. The terms metachromatic, sudanophilic, orthochromic, etc., refer to the distinctive products of myelin degeneration and staining characteristics (or lack thereof) of the white matter in the individual leukodystrophies. As emphasized earlier, these are distinguished from the cerebral gray matter diseases (poliodystrophies), which have a different mode of presentation—seizures, myoclonus, chorea, choreoathetosis, and tremor being prominent. Instead, recognition of the entire group of leukodystrophies is based on symptoms and signs attributable to the interruption of tracts (corticospinal, corticobulbar, cerebellar peduncular, sensory) and visual pathways (optic nerve, optic tract, geniculocalcarine) and the infrequency or absence of seizures, myoclonus, and spike-and-wave abnormalities in the EEG. However, this distinction is not infallible, particularly in the later stages of the disease.
The syndrome of progressive spasticity and rigidity with spastic dysarthria and pseudobulbar palsy poses a difficult diagnostic problem. One’s first impulse is to assume the presence of a corticospinal disorder, especially if tendon reflexes are brisk, but frequently the plantar reflexes are flexor and the facial reflexes are not enhanced (“pseudo-pseudobulbar palsy,” a term we attribute to Marsden). In addition, unusual postures and a more plastic type of rigidity may occur, consistent with an extrapyramidal condition. Adrenomyeloneuropathy is another syndrome that combines reduced or absent tendon reflexes and Babinski signs, signifies a combination of corticospinal and peripheral nerve lesions, and is highly characteristic of metachromatic leukoencephalopathy.