Specificity of the urine inhibitor test for Leigh's disease

Pincus, Jonathan H.; Cooper, Joel; Piros, Katalin; Turner, Virginia

doi:10.1212/wnl.24.9.885

Cited by 37 publications

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“…Our study appears to confirm that the investigated population is at high risk for development of SNE, since the incidence of the inhibitor factor (14 out of 68, or 20%) was significantly higher than in a control population (4%) [19]. A strong correlation was found between the incidence of inhibitor factor and the presence of neurological abnormalities in family members investigated.…”

Section: Discussionsupporting

confidence: 84%

“…Two showed inhibition in the equivocal range ( 2 5 to 40%), while 2 individuals lacked the inhibitor factor by urine assay. The TDP-ATP phosphoryltransferase inhibitor factor has proved useful in the diagnosis of SNE during life [ 3 , 4 , [17][18][19] and has correlated with pathological evidence of the disease. False positive and false negative results have been reported [17-191.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic leigh disease: A genetic and biochemical study

Plaitakis

Whetsell

Cooper

et al. 1980

Annals of Neurology

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The large family of a 21-year-old man who died of Leigh disease was investigated for evidence of neurological abnormalities and presence of the adenosine triphosphate-thiamine diphosphate phosphoryltransferase inhibitor factor. Of 217 persons (seven generations) included in the pedigree, 68 were examined neurologically and biochemically. Fourteen (20%), 5 of whom had abnormal neurological findings, were found to excrete the inhibitor factor. Clinical manifestations varied from severe neurological affliction to subtle deficits. A chronic relapsing course was frequently encountered, with exacerbations occurring in association with apparent metabolic stress. Parental consanguinity was identified in the propositus as well as in other family members with neurological abnormalities. Males and females were affected, and no vertical transmission of the trait was found. These multigenerational data suggest that Leigh disease in adults is inherited in an autosomal recessive manner and has variable degrees of expression with a wide spectrum of neurological manifestations.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Chronic leigh disease: A genetic and biochemical study

Plaitakis

Whetsell

Cooper

et al. 1980

Annals of Neurology

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“…A sample of urine from the propositus did not contain the inhibitor which has been proposed as a test for Leigh's syndrome (29). The necrotic foci, glial reaction, and capillary proliferation characteristic of Leigh's encephalomyelopathy were absent in the brains of the two sisters of the propositus (27).…”

Section: Discussionmentioning

confidence: 93%

Sensitivity to Carbohydrate in a Patient with Familial Intermittent Lactic Acidosis and Pyruvate Dehydrogenase Deficiency

et al. 1976

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Pediat. Res. 10: 7 13-720 (1976) Alaninuria metabolic acidosis inborn e r r o r of metabolism pyruvate dehydrogenase deficiency lactic acidosis skin fibrosis m e n t a l retardation Extract diet containing 65% carbohydrates precipitated a severe episode of lactic acidosis and whose two sisters died of the same disorder. His A 9-year-old boy with severe mental and growth retardation and cultured skin fibroblasts proved to be deficient i n PDH activity, diffuse neurologic damage had minimal elevation of blood pyruvate (0.21 mM) and lactate (2.1 mM) on a normal diet hut developed CASE REPORTS life-threatening lactic acidosis (pH 7.14; lactate 21.0 mM) on a diet containing 65% carbohydrates and 15% fat. Subsequently, CASE I blood pyruvate levels rose significantly higher than in 16 control subjects during a glucose tolerance test whereas the glucose levelsThe propositus. JB. was born without complications at term were normal. after a normal pregnancy. Birth weight. length, and head circumTwo sisters died with spontaneous lactic acidosis and an otherwise ference were normal. He was hypoactive and hypotonic and was similar clinical course. ~h~i~ brains at autopsy were severely said to have a "peculiar" odor. Psychomotor development virtualdeficient in myelin but showed no evidence for active &myelination.ly ceased by 3 months of age; growth decelerated at 2 years and Cultured skin fibroblasts from the patient oxidized respiratory infections despite 4 years in a state hospital. Severe normally. ~h~ activity of the pyruvate dehydrogenase complex in neurologic deficits were noted early and were similar to those cell-free extracts (59* 16 pmol/min/mg protein) was significantly described below. less than that for control subjects (389* 35; P < 0.001), but the When seen at age 8.5 years, the patient was severely stunted in activities pyruvate decarboxylase and of the 2-oxoglutarate de-growth, profoundly retarded. had flexion deformities of the hands hydrogenase complex were within the normal range. Pyruvate de-and feet, but had no dysplastic features. Weight was 11.4 kg; hydrogenase levels in extracts of the parents9 cells were midway height, 95 cm; and head circumference. 50 cm. His pulse rate was between those of the patients and the control subjects. ~i~i~~ never found to be below 100. He appeared to hear and see and had experiments, addition of excess cofactor, and studies of activation no evidence of optic atrophy or retinitis pigmentosa. He could not failed to implicate a soluble inhibitor, abnormal binding of co-turn over, sit up. hold his head up, follow, or transfer objects. His factors, or defective activation as causes of the reduced enzyme posture was dystonic with continual choreoathetoid movements. activitv.He tended to hold his muscles rigidly but was profoundly ~h~" data are consistent an inherited defect in the second hypotonic when he relaxed. There were bilateral extensor plantar enzyme of the pyruvate dehydrogenase complex, lipoate acetyl-reflexes. The deep tendon reflexes were normal to slightly in...

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“…Pincus et al (1974) suggested an abnormality in thiamine metabolism and proposed a urine inhibitor test as specific for Leigh's disease, but this specificity was later disclaimed. Pincus et al (1974) suggested an abnormality in thiamine metabolism and proposed a urine inhibitor test as specific for Leigh's disease, but this specificity was later disclaimed.…”

Section: Discussionmentioning

confidence: 99%

Cytochromec oxidase deficiency in three patients with Leigh's disease

Rocco¹,

Veneselli²,

Ciccone³

et al. 1988

J of Inher Metab Disea

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Sabacute necrotizing encephalomyopathy, first reported by Leigh more than 30 years ago, is an autosomal recessive disorder characterized by multiple symmetrical loci of incomplete necrosis (spongy degeneration) in brainstem, spinal cord, basal ganglia and cerebellum. The clinical picture is heterogeneous, depending on the variability of lesions, but usually it consists of disorders of respiratory rhythm, nuclear and supranuclear oculomotor paralysis, other signs of cranial nerve dysfunction, abnormal movements, ataxia and optic atrophy.Different biochemical causes have been proposed: defects of pyruvate carboxylase, pyruvate dehydrogenase complex and the respiratory chain are reported in patients affected with Leigh's disease. We report here three new patients, in whose fibroblasts we found partial defects of cytochrome oxidase. We emphasize that the association of typical neuroradiological lesions with one of the proposed biochemical markers can lead to premortem diagnosis in living patients and to early genetic counselling. CASE REPORTCase 1: R. Cosimo is the first child of healthy, related parents (first cousins). He had normal psychomotor development during the first 2 years of age; after which time he began to show failure to thrive, vomiting, arm and head tremor and jerky eye movements. At the age of 3 years he was first admitted to our department. Clinical examination revealed hypotonia, paralysis of vertical gaze, horizontal nystagmus, cerebellar intentional tremor, inco-ordination and hyporeflexia; mental abilities were quite normal.Lactic acidaemia ranged between 40 and 30.3 mg dL -1 (normal values 5-20) and pyruvic acidaemia between 0.56 and 0.38 mg dL -1 (normal values 0.36--0.59). CSF proteins were 43 mg dL -a with normal electrophoretic pattern. The boy continued to deteriorate and at the age of 4 years he was readmitted to hospital. At this time the clinical picture consisted of cerebellar ataxia, optic atrophy and mental deterioration; nerve conduction velocity was decreased. CT scan showed typical basal ganglia lesions (Figure 1). The child is still alive at the age of 6 years and 189 Journal of Inherited Metabolic Disease. ISSN 0141-8955.

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Specificity of the urine inhibitor test for Leigh's disease

Cited by 37 publications

References 0 publications

Chronic leigh disease: A genetic and biochemical study

Chronic leigh disease: A genetic and biochemical study

Sensitivity to Carbohydrate in a Patient with Familial Intermittent Lactic Acidosis and Pyruvate Dehydrogenase Deficiency

Cytochromec oxidase deficiency in three patients with Leigh's disease

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