Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two children are described who suffered from episodes of metabolic acidosis and progressive mental and motor deterioration. The patients showed periodic elevation of blood lactate, pyruvate and alanine, which was accompanied by vomiting, hypotonia or convulsions. The concentrations of lactate and pyruvate in cerebrospinal fluid were found to be increased. Liver biopsies revealed a decrease in pyruvate carboxylase activity and normal pyruvate decarboxylase activity. No inhibitor of TPP-ATP phosphoryl transferase was detected in urine from the patients. These findings suggest that congenital lactic acidosis due to pyruvate carboxylase deficiency is probably a different disease entity from Leigh's encephalomyelopathy. A possible mechanism of brain damage caused by a defect in pyruvate carboxylase is postulated.
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PMID:Congenital lactic acidosis due to pyruvate carboxylase deficiency: absence of an inhibitor of TPP-ATP phosphoryl transferase. 20 66

Fourteen new cases of cytochrome oxidase (COX)-associated Leigh syndrome (LS) are combined with 20 reported cases to describe the clinical, laboratory, and radiological features of this devastating metabolic condition. Three clinical stages are identified. Most patients have normal neurological development during the first 8-12 months (stage I). Somatic complaints are common, including chronic diarrhea, recurrent vomiting, anorexia, and decelerating body and head growth. The second stage evolves during late infancy and early childhood when motor regression becomes evident. Eye signs, altered breathing patterns, pyramidal, extrapyramidal, and cerebellar signs emerge and sudden clinical deterioration occurs during intercurrent infectious or metabolic stress. The last stage may extend from 2 to 10 years and is manifested by extreme hypotonia, swallowing difficulties and undernutrition. Feeding assistance is necessary and seizures may occur. The CSF lactate concentration is consistently elevated and MRI abnormalities are seen in the subcortical structures. COX deficiency affects most tissues, but is not always generalized. For example, 3 patients with a cardiomyopathy had normal COX activity in cultured skin fibroblasts. Nearly normal amounts of cross-reacting material are present by ELISA and immunoblot analyses. Parental consanguinity has been found in several families, the hereditary pattern is recessive and males are affected more commonly (2:1). The biomolecular abnormality causing COX deficiency in LS is unknown, but the available evidence implicates a nuclear-encoded protein that affects the structure or the stability of the holoenzyme complex.
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PMID:Cytochrome c oxidase-associated Leigh syndrome: phenotypic features and pathogenetic speculations. 165 84

Subacute necrotizing encephalomyelopathy (SNE; Leigh's disease), though a defined entity in neuropathological and morphological terms, is characterized by high clinical heterogenity. SNE of infancy can be defined and diagnosed on the basis of clinical symptoms more readily than juvenile and adult forms. Four patients with SNE displayed combinations of recurrent vomiting, difficulty in swallowing, failure to thrive, impairment of ocular innervation, muscle tone regulation and central regulation of respiration. These symptoms, particularly in combination, point to a disorder of the brainstem and basal ganglia. In addition, all four patients were suffering from lactic acidosis. Other possible indicators, but not in all 4 patients, were abnormal CT brain scans, impaired nerve conduction velocity, elevated CSF protein levels and enlarged mitochondria in muscle cells. Abnormal brainstem auditory evoked potentials have proved to be one of the best criteria for early diagnosis of brainstem lesions. Enzyme assays of pyruvate degradation in cultured skin fibroblasts revealed diminished activity of the pyruvate dehydrogenase complex in one patient (52 pmol/mg protein x min; median range 313, 82-917, n: 58). This paper summarizes the findings and proposes primary and secondary criteria of assistance in establishing an initial clinical diagnosis of infantile SNE. As no common pathogenetic mechanisms have yet been recognized and no uniform diagnostic markers are yet available, the diagnosis still requires confirmation by histological examination of brain and brainstem, as was the case with all four patients presented.
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PMID:[Diagnostic criteria in classical infantile subacute necrotizing encephalomyelopathy (Leigh's disease)]. 271 38

A new patient with Leigh's syndrome (subacute necrotizing encephalomyelopathy due to pyruvate dehydrogenase complex deficiency) is presented. A Turkish boy of consanguinously married healthy parents developed progressive muscle weakness since infancy. At the age of 3 years he was unable to sit, stand or walk. Clinical examination showed general muscle weakness, hypotonia, muscle hypotrophy, bilateral ptosis, partial bilateral external ophthalmoplegia, nystagmus, intention tremor and hypoactive tendon reflexes. The EEG showed diffuse slowing, the cerebral CT scan disclosed mild hydrocephalus e vacuo. Motor nerve conduction velocity was slightly decreased, the EMG revealed signs of neuropathy. In the biopsied muscle only a mild hypotrophy of type 2 fibres was found, no abnormal mitochondria could be detected. The sural nerve was slightly abnormal: loss of large myelinated axons, loss of unmyelinated nerves. CSF protein was elevated to 80 mg/dl, protein electrophoresis revealed the pattern of markedly impaired blood-CSF barrier. Serum lactate and pyruvate were permanently elevated. In the urine the excretion of alanine was raised. The clinical state deteriorated during intercurrent infections; somnolence, vomiting and Cheyne-Stoke's respiration occurred. At the age of 3 1/2 years the child died of pneumonia. In the liver tissue a decreased activity of the pyruvate dehydrogenase complex was found. Neuropathological examination of the brain demonstrated wide-spread changes of Leigh's spongiform encephalopathy. Several enzyme deficiencies have hitherto been associated with Leigh's syndrome: This patients confirms earlier findings that a subgroup of Leigh's syndrome is caused by pyruvate dehydrogenase complex deficiency.
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PMID:[Leigh's subacute necrotizing encephalomyelopathy due to decreased activity of the pyruvate dehydrogenase complex]. 312 26

A 55-year-old man with a subacute onset of slurred speech, ataxia, nystagmus, extrapyramidal rigidity, decreased tendon reflexes, vomiting, bilateral optic atrophy, and clonic jerks died of bronchopneumonia and respiratory failure. Neuropathological examination showed lesions characteristic of subacute necrotizing encephalopathy. Clinicopathological observations of reported cases of Leigh's syndrome in the adult are reviewed.
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PMID:Leigh's syndrome in an adult. 652 Jun 17

A 28-month-old Korean girl developed a rapidly progressive disease, characterized by disturbance of consciousness, tremor, nystagmus, ophthalmoplegia, irregular deep respiration and vomiting. The patient succumbed 2 weeks after the onset of the illness. CT scan disclosed bilaterally symmetrical, low density lesions in the white matter and lateral basal ganglia. Distinctive histopathological findings at postmortem included spongiotic necrosis of the neuropil, marked capillary vascularity, persistence of relatively normal neurons in severely damaged zones, and comparatively little astrocytosis. The bilaterally symmetrical distribution of these changes in the putamen and periaqueductal gray matter of the midbrain were compatible with Leigh's disease.
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PMID:Leigh's subacute necrotizing encephalomyelopathy: possible diagnosis by CT scan. 731 63

An example of subacute necrotizing encephalopathy, the fifth case in Thailand, was recorded. A 7-month-old boy presented clinically with vomiting, lethargy, respiratory difficulty, deteriorated consciousness, and hypotonia. The CT brain scan disclosed bilateral symmetrical radiolucencies in the basal ganglia, especially the lentiform nuclei, and thalami. Postmortem examination of these areas as well as the periaqueductal region revealed subacute necrotizing encephalopathy. It was characterized by necrosis, gliosis, and status spongiosus of the neuropil with relatively preserved neurons, and hyperplasia of small blood vessels as well as endothelium. As far as we are aware, the vast majority of abnormalities in the basal ganglia visualized by CT brain imaging often show calcific foci or high attenuation with asymmetrical distribution. Bilateral symmetrical lesions of low density are rare. We reported such an abnormality in a postmortem proven case of Leigh's disease. To recognize this finding should lead to correct antemortem diagnosis of the latter.
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PMID:Subacute necrotizing encephalopathy (Leigh's disease) in a child with particular reference to CT finding. 775 78

A two-and-a-half-year-old male child presented with recurrent attacks of intractable vomiting, psychomotor retardation since 14 months of age. He had also lower cranial nerve palsy and corticospinal involvement. Magnetic resonance imaging had shown multiple well circumscribed areas of hypointusity in T1 weighted image which were brightly hyperintense in heavily T2-weighted image. The lesions were seen in basal ganglia, thalamii and brainstem and spared mamillary bodies. Magnetic resonance spectroscopy demonstrated lactate peak in the affected areas confirming the diagnosis of Leigh's disease. The child responded well to large dose of vitamin 'B' therapy.
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PMID:Antemortem diagnosis of Leigh's disease: role of magnetic resonance studies. 1083 40

A 15-month-old female child presented with sudden onset cough and hyperventilation along with evidence of metabolic acidosis. She had past history of recurrent vomiting, episodes of abnormal posturing, difficulty in deglutition and regression of milestones since 12 months of age. CT scan of the brain revealed hypodense lesions in bilateral basal ganglia and on MRI there were T2 hyperintensities in bilateral lentiform nuclei, caudate nuclei, thalamus, red nuclei and dentate nuclei. Biochemical examination revealed persistently elevated serum lactate levels with high lactate/pyruvate ratio. Resuscitative measures were of no avail and the child succumbed to the illness on the second day of admission. Neuropathological examination at autopsy demonstrated marked spongiosis, focal necrosis, endothelial proliferation, reactive astrogliosis and extensive demyelination involving bilateral basal ganglia, midbrain and spinal cord which were typical of Leigh's sub acute necrotizing encephalomyelopathy.
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PMID:Leigh's syndrome. 1557 26

Diffuse astrocytoma with bilateral thalamic involvement is extremely rare. We present a case of 10 years old female who presented with decreased mentation, dysarthria, decreased performance at school and later on with seizures. MRI scans were performed twice and were reported as Leigh's disease and hemimegalencephaly respectively. Patient presented again with complaint of unconsciousness, vomiting and chest congestion. No further imaging was performed. Biopsy showed grade III Astrocytoma with bilateral thalamic involvement. Patient was admitted to intensive care unit but could not survive and expired.
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PMID:Diffuse bilateral thalamic astrocytoma. 1737 6


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