1/44. Necrotizing encephalopathy and macrocephaly with mitochondrial complex I deficiency.A neonate presented in the first weeks after birth with vomiting. He was unresponsive, with hypotonia, macrocephaly, and lactic acidosis. The cranial computed tomographic scan revealed a hypodense brain, with increased brain volume and extensive cerebral edema. He died at 6 weeks of age; postmortem examination revealed necrotizing encephalopathy with marked brain edema, spongiosis, thalamic necrosis, and basal ganglia calcifications. Enzyme studies of the mitochondrial respiratory chain revealed complex I deficiency in both muscle and liver.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
2/44. Unique astrocytic inclusion in a 2 month-old baby showing Leigh-like brain lesions with lactic acidosis.An unique cytoplasmic inclusion was found in astrocytes of a 2-month-old female baby who showed Leigh-like brain lesions with lactic acidosis, hypoglycemia and hepatomegaly. Although a defective enzyme was not determined, a metabolic disorder was suggested from clinicopathological observations. Symmetrically distributed lesions consisting of marked gliosis and proliferation of capillaries were observed in the basal ganglia, thalami and tegmentum. The astrocytic cytoplasmic inclusion was exclusively found in the cerebral and cerebellar white matter, where myelination was immature. The inclusion was round and eosinophilic, and positive for glial fibrillary acidic protein, vimentin, alphaB-crystallin, S-100 protein and microtubule associated protein 1B, immunohistochemically. An electron microscopic examination revealed an accumulation of intermediate filaments, ribosome and rough endoplasmic reticulum in the inclusion. The characteristic of this inclusion is different from that of other reported inclusions. The inclusion showed positive immunoreaction against CuZn superoxide dismutase, catalase, advanced glycation end-product and 4-hydroxy-2-nonenal antibodies, which suggest that oxidative stress is involved in the genesis of the inclusion.- - - - - - - - - - ranking = 85.709286446529keywords = metabolic disorder, brain (Clic here for more details about this article) |
3/44. leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency.Three cases of leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay. The diagnosis was made on the basis of the clinical characteristics, biochemical abnormalities, and typical brain magnetic resonance imaging with symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) deficiency was demonstrated in muscle tissue in all patients and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was present in these patients since only one had a SURF-1 gene mutation. The clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in one of the described cases is of extreme interest; to our knowledge, this association has never been reported in the literature.- - - - - - - - - - ranking = 0.66666666666667keywords = brain (Clic here for more details about this article) |
4/44. lactic acid elevation in extramitochondrial childhood neurodegenerative diseases.We report three children, each of whom seemed to have a primary mitochondrial disorder at presentation but was eventually diagnosed with an extramitochondrial inherited metabolic disease. The first patient presented at 6 months with developmental delay. magnetic resonance imaging showed an abnormal signal in the white matter, and magnetic resonance spectroscopy showed elevated lactate peaks. A muscle biopsy showed complex IV deficiency, but leukocyte measurement of galactosylceramide beta-galactosidase activity was markedly diminished, consistent with Krabbe's disease. The second patient presented at birth with seizures and later had developmental delays. There was brain atrophy on neuroimaging. serum and cerebrospinal fluid lactate levels were elevated. She had persistently elevated urine thiosulfate, which was diagnostic for molybdenum cofactor deficiency. The third child presented at 2 months with seizures and hypotonia. magnetic resonance imaging showed an abnormal signal in the basal ganglia and surrounding white matter, whereas magnetic resonance spectroscopy showed elevated lactate peaks. A brain biopsy was diagnostic for Alexander's disease. These cases and others in the literature suggest that lactic acid elevation in the central nervous system can be found in a number of extramitochondrial neurologic diseases. Such diseases would constitute a third category of lactic acidosis.- - - - - - - - - - ranking = 0.66666666666667keywords = brain (Clic here for more details about this article) |
5/44. congenital disorders of glycosylation (CDG) may be underdiagnosed when mimicking mitochondrial disease.congenital disorders of glycosylation (CDG) and mitochondrial diseases are multisystem disorders with clinical characteristics that may overlap. We present four patients with CDG whose phenotypes suggested the diagnosis of a mitochondrial disease. patients 1 and 2 are siblings with hemiplegic headache, stroke-like episodes, lactic acidaemia and history of maternal migraine; their initial clinical diagnosis was melas syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes). Patient 3 suffers from ataxia, neuropathy, ophtalmoplegia and retinitis pigmentosa suggestive of NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. Patient 4 presented with neurological regression mimicking leigh disease, with ptosis, myoclonus, ataxia and brainstem and cerebellar atrophy. Screening for mitochondrial disease including enzyme and mtDNA investigations on muscle biopsy were performed on patients 1, 2 and 4 with normal results. However, evidence for a glycosylation disorder was substantiated by an increased carbohydrate deficient transferrin (CDT). The isoelectric focussing pattern of serum sialotransferrin was typical of CDG type I in patients 1, 2 and 3 and was shifted towards the less sialylated bands in case 4. A deficiency of phosphomanomutase (PMM) confirmed the diagnosis of CDG-Ia in patients 1, 2 and 3, who are compound heterozygous for mutations R141H/T237M (patients 1 and 2) and R141H/P113L (Patient 3). In Patient 4, PMM activity was normal, and further enzymatic and molecular studies are underway. As the search for the primary defect in mitochondrial diseases is often unsuccessful, the pool of mitochondrial patients that remain without definite diagnosis might include CDG cases. Routine screening for CDG may avoid precocious invasive investigations.- - - - - - - - - - ranking = 0.33333333333333keywords = brain (Clic here for more details about this article) |
6/44. prenatal diagnosis of pyruvate dehydrogenase deficiency using magnetic resonance imaging.INTRODUCTION: Pyruvate dehydrogenase deficiency is an inherited inborn error of metabolism associated with early neonatal death and long-term neurologic sequelae in survivors. prenatal diagnosis currently relies on isolation of fetal cells for subsequent genetic and/or biochemical studies. magnetic resonance imaging and magnetic resonance spectroscopy have been used on occasion for both postnatal diagnosis and management of pyruvate dehydrogenase deficiency. We illustrate a case in which these non-invasive modalities also prove useful for prenatal diagnosis of this condition. CASE: A 31-year-old multipara with a history of two prior infants affected with pyruvate dehydrogenase deficiency presented with a spontaneous dichorionic, diamniotic twin pregnancy. magnetic resonance imaging and magnetic resonance spectroscopy were performed on both fetuses. magnetic resonance imaging of the presenting (male) fetus demonstrated mild ventriculomegaly, increased extracerebrospinal fluid, and decreased cortical sulcation and gyration. The non-presenting (female) fetus was structurally normal. magnetic resonance spectroscopy spectra were obtained for both fetuses, and were normal. The diagnosis of pyruvate dehydrogenase deficiency was made in the presenting fetus after delivery on the basis of subsequent mortality from severe lactic acidosis. CONCLUSION: Prenatal MR imaging of the fetal brain can be used for prenatal diagnosis in fetuses at risk for pyruvate dehydrogenase deficiency. Prenatal MR spectroscopy, although technically feasible, does not appear to have a role in the prenatal diagnosis of this condition.- - - - - - - - - - ranking = 0.33333333333333keywords = brain (Clic here for more details about this article) |
7/44. Pathogenic mechanism, prophylaxis, and therapy of symptomatic acidosis induced by acetazolamide.BACKGROUND: acetazolamide, a noncompetitive carbonic anhydrase inhibitor, can produce symptomatic acidosis and bone marrow suppression by a mechanism that is still unknown. This presentation occurs in the elderly, patients with renal or liver failure, people with diabetes, and newborns. The objective of this study was to understand the pathogenic mechanism of these adverse effects and to propose a possible prophylaxis and therapy. methods: Four human clinical cases were studied, and one animal experiment was performed. Four preterm newborns with posthemorrhagic ventricular dilation developed severe metabolic acidosis after treatment with acetazolamide. The acidosis suddenly disappeared after a packed red blood cell transfusion. Metabolic studies were performed in one patient and in newborn guinea pigs treated with 200 mg/kg acetazolamide. RESULTS: acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low beta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. The acquired enzymatic injury resulting from the inhibition of mitochondrial carbonic anhydrase v that provides bicarbonate to pyruvate carboxylase can produce tricarboxylic acid cycle damage. We demonstrate that the dramatic disappearance of metabolic acidosis and normalizing metabolism after blood transfusion were due to the citrate contained in the packed red blood cell bag. This hypothesis was confirmed by animal experimentation. We argue that the metabolic disorder and bone marrow suppression may be related. CONCLUSION: We demonstrate how acetazolamide can lead to symptomatic metabolic acidosis and probably to bone marrow suppression. We suggest citrate as a possible prophylaxis and treatment for these adverse reactions.- - - - - - - - - - ranking = 84.042619779863keywords = metabolic disorder (Clic here for more details about this article) |
8/44. An inherited metabolic disorder presenting as ethylene glycol intoxication in a young adult.Despite the abundance of reports emerging in the literature on metabolic disorders, some disorders remain undiagnosed or misdiagnosed, not only in clinical pathology but also in forensic pathology. The authors report a patient who had recurrent episodes characterized by nausea, vomiting, and signs of dehydration necessitating admission to the hospital. At each admission, he was found to have lactic acidosis. On the first admission, glycolic acid was detected in his blood and he was diagnosed as having ethylene glycol intoxication. Only at the third admission, 2 years after the first, was the possibility of an underlying metabolic disorder considered. Laboratory investigations showed a deficiency of complex I in the mitochondrial oxidative phosphorylation. Possible medicolegal implications are discussed.- - - - - - - - - - ranking = 504.25571867918keywords = metabolic disorder (Clic here for more details about this article) |
9/44. A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the PDX1 gene.We report a case of neonatal congenital lactic acidosis associated with pyruvate dehydrogenase E3-binding protein deficiency in a newborn girl. She had a severe encephalopathy, and magnetic resonance imaging of the brain showed large subependymal cysts and no basal ganglia lesions. She died 35 days after birth. We detected a novel homozygous deletion (620delC) in the PDX1 gene, which encodes for the E3BP subunit of the pyruvate dehydrogenase complex.- - - - - - - - - - ranking = 0.33333333333333keywords = brain (Clic here for more details about this article) |
10/44. Mitochondrial angiopathy in a family with MELAS.A family with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike epidoses (MELAS) affecting mother, son and daughter is described. Biochemical studies on muscle biopsy specimen in one patient revealed nadh dehydrogenase (complex I) deficiency. A mitochondrial angiopathy could be demonstrated by brain and muscle biopsy. It is suggested that the mitochondrial angiopathy is the basic pathogenic mechanism of impaired cerebral circulation in MELAS.- - - - - - - - - - ranking = 0.33333333333333keywords = brain (Clic here for more details about this article) |
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