Stroke, hemiparesis and deficient mitochondrial ?-oxidation

Abstract

We describe on a 3-year-old child referred for evaluation and therapy of a cerebral vascular accident with residual hemiplegia and partial epilepsy. Metabolic investigations initially showed normal urinary organic acids as well as normal blood and urinary amino acids. Blood carnitine fractions had been pathological and a secondary carnitine deficiency was diagnosed and treated by oral L-carnitine supplementation. During carnitine treatment, abnormal urinary acylcarnitine profiles were noticed with excessive amounts of several carnitine esters including propionylcarnitine, butyryl- and/or isobutyryl-carnitine, isovaleryl- and/or 2-methylbutyryl-carnitine, hexanoylcarnitine and octanoylcarnitine. Subsequently, an urinary organic acid profile suggestive of glutaric aciduria type II was recorded during a clinical decompensation crisis. Morphological and biochemical studies on skeletal muscle and skin fibroblasts were performed and confirmed the existence of a defect of the mitochondrial beta-oxidation pathways with lipidic myopathy, reduced palmitate and octanoate oxidation rates in cultured fibroblasts. Glutaric aciduria type II increases the list of metabolic disorders characterized by hemiplegia and other sequelae of brain ischaemia such as stroke-like episode, seizures, aphasia, ataxia and myoclonia, similar to those seen in MELAS.

Mitochondrial Disease

“…1,[73][74][75] Stroke often involves the occipital or parietal lobes and usually follows a nonvascular distribution that is seen on a head CT scan. 1,[73][74][75] Stroke often involves the occipital or parietal lobes and usually follows a nonvascular distribution that is seen on a head CT scan.…”

“…7,51,55,89,90 Lactate levels are increased when normal oxidative phosphorylation is disrupted and NADH concentration increases. 7,14,74,77,90 Low levels of carnitine suggest carnitine deficiency or an abnormality of CPT I or II, which may be isolated or may occur concomitantly with diseases of oxidative phosphorylation or hyperlactemia. However, normal lactate levels and a normal lactate-to-pyruvate ratio do not exclude mitochondrial disease.…”

Case 39-1998

“…Certain organic-acid disorders have been associated with stroke-like episodes, including methylmalonicacidemia, propionicacidemia, isovalericacidemia, and two forms of glutaricaciduria (types I and II). 10,11 However, the clinical features of these disorders, which include an extrapyramidal syndrome characterized by dystonia and tremor and pyramidal-tract signs such as spastic quadriparesis, were absent in this case. 12 Neuroimaging shows predominant involvement of basal ganglia in cases with stroke, 13,14 and diffuse, deep white-matter involvement is typical.…”

Inherited Metabolic Disorders and Stroke Part 2

“…33 Stroke in a 3-year-old child with GAT2 has been described. 34 Because of the low incidence of GAT2, risk factors for and pathogenesis of stroke in this disorder have not been defined.…”

“…Patients with GAT2 are treated with a lowfat, low-protein, and high-carbohydrate diet. 34 lism, ammonia, into urea. This process occurs partly in the mitochondrion and partly in the cytoplasm of cells.…”