1/104. A severely affected infant with absence of cysteinyl leukotrienes in cerebrospinal fluid: further evidence that leukotriene c4-synthesis deficiency is a new neurometabolic disorder.leukotrienes are potent oxygenated metabolites derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. They comprise the cysteinyl leukotrienes (LTC4, LTD4, LTE4) and LTB4. The rate limiting step in the formation of cysteinyl leukotrienes is the conversion of LTA4 to LTC4 catalyzed by the enzyme LTC4 synthase. Recently, the first inborn error of leukotriene synthesis, LTC4-synthesis deficiency, has been identified in a patient with a fatal developmental syndrome. We report on an additional infant presenting with severe muscular hypotonia, symmetrical extension in the lower extremities and psychomotor retardation who died at the age of 6 months. Despite intensive investigations no specific diagnosis could be made. leukotrienes were subsequently analyzed in the cerebrospinal fluid. Concentrations of LTC4, LTD4 and LTE4 were below the detection limit (< 5 pg/ml) whereas LTB4 was found to be in the upper normal range. The absence of cysteinyl leukotrienes with normal LTB4 concentration in cerebrospinal fluid is unique and seems to be pathognomonic for LTC4-synthesis deficiency. Our patient most likely represents the second case described so far with this condition. This report provides further evidence that LTC4-synthesis deficiency represents a new neurometabolic disorder.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/104. Neonatal type of nonketotic hyperglycinemia.Two infants with the neonatal type of nonketotic hyperglycinemia that had manifested as early neonatal consciousness disturbance are presented. Transient hyperammonemia had been detected in both initially. High levels of glycine in plasma and cerebrospinal fluid disturb the nervous system, causing variable manifestations of this disease. Both cases were complicated by intracranial hemorrhage, which has never before been reported. After treatment with sodium benzoate and dextromethorphan, some neurologic improvement was observed, although the glycine levels did not lower. Recent clinical trials are reviewed, and because of the unfavorable outcomes, the special need for prenatal diagnosis is highlighted.- - - - - - - - - - ranking = 4.3469298885517keywords = hyperglycinemia (Clic here for more details about this article) |
3/104. 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 = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
4/104. Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features.Adenylosuccinase deficiency is an autosomal recessive inherited defect of purine synthesis. In enzyme deficient patients, two normally undetectable compounds, succinylaminoimidazole carboxamide riboside and succinyladenosine, accumulate in urine, cerebrospinal fluid and, to a minor extent, in plasma. Analysing 150 highly selected urine specimens from patients with unidentified neurogenerative disorders we discovered the first two German cases of adenylosuccinase deficiency. The deficiency causes moderate to severe mental retardation, often accompanied by epileptic seizures and/or autistic features, and is occasionally associated with growth retardation and muscular hypotonia. Of the two German cases we present here, one patient fits into the clinical picture outlined by previous reports. The other patient, however, shows a pattern of symptoms so far undescribed: severe early infantile epileptic encephalopathy with reduced myelination. On mutation analysis this patient is the first to reveal a 39 base pair deletion in the adenylosuccinase gene in contrast to the point mutations detected in previous cases. Adenylosuccinase deficiency may be an underdiagnosed metabolic disorder with variable expression. This should be taken into consideration in patients with unclassified neurological conditions.- - - - - - - - - - ranking = 1.1428571428571keywords = deficiency (Clic here for more details about this article) |
5/104. Late infantile acid maltase deficiency: a case report.A five-year-old boy with late-infantile (juvenile) form of acid maltase deficiency is presented. His symptoms were restricted to skeletal muscle. There is commonly a correlation between the amount of residual acid maltase activity and the severity of the clinical picture. Although the residual enzyme level was very low in our patient, no progression of his neurological findings have been observed during the follow-up period of two years.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
6/104. Fumaric aciduria: clinical and imaging features.Fumaric aciduria (fumaric acidemia, fumarase deficiency) is a rare inborn error of metabolism caused by deficient activity of fumarate hydratase, one of the constituent enzymes of the Krebs tricarboxylic acid cycle. We describe the clinical and imaging features of this disease arising from a consanguineous pedigree in 8 patients in the southwestern united states. Thirteen patients have been previously described in the medical literature. Our patients presented with an early infantile encephalopathy with profound developmental retardation and hypotonia, and most experienced seizures. Previously unreported characteristics described here include structural brain malformations, dysmorphic facial features, and neonatal polycythemia. magnetic resonance imaging showed multiple abnormalities, including diffuse polymicrogyria, decreased cerebral white matter, large ventricles, and open opercula. Fumaric aciduria should be included in the differential diagnosis of inborn errors of metabolism that cause cerebral malformations and dysmorphic features. The possibility that inborn errors of energy metabolism may cause structural malformations deserves increased recognition.- - - - - - - - - - ranking = 0.22236378365262keywords = deficiency, acidemia (Clic here for more details about this article) |
7/104. A patient with mitochondrial myopathy associated with isolated succinate dehydrogenase deficiency.We report on a boy with normal mental development who had muscle hypotonia and congenital dislocation of the hip and knee joints. Histochemical and biochemical examinations of his muscle specimen revealed no succinate dehydrogenase (SDH) activity. Since the NADH cytochrome c reductase and cytochrome c oxidase activities were normal, we concluded that he had an isolated SDH deficiency. Our patient provides further evidence for the clinical variability of this disorder.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
8/104. Fetal-onset severe skeletal muscle glycogenosis associated with phosphorylase-b kinase deficiency.We report on a premature newborn girl delivered after 32 weeks of gestation by cesarean section after sparse limb movements, fetal tachycardia and late heart rate decelerations had suggested fetal distress. Following 1 day of mechanical ventilation, adequate pulmonary gas exchange was achieved by spontaneous breathing. Main symptoms were virtually complete absence of spontaneous movements, increased flexor tonus of the extremities, and hypotonia of the trunk. Inability to suck or swallow required nasogastric gavage feeding. There were no hypoglycemic episodes. echocardiography revealed normal myocardial function. creatine kinase was 237 U/I at 2 days of life, declining to normal values thereafter. Muscle biopsy revealed increased glycogen storage with subsarcolemmal glycogen deposits and low phosphorylase-a activity while total phosphorylase was normal after in vitro activation, suggestive of phosphorylase-b kinase deficiency. No mutation was detected in exon 1 of the myophosphorylase gene. No psychomotor development was observed, and the infant died of central apnea at 3 months of age.- - - - - - - - - - ranking = 0.71428571428571keywords = deficiency (Clic here for more details about this article) |
9/104. tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation.tyrosine hydroxylase (TH) deficiency is generally considered as a cause of the autosomal recessive form of dopa-responsive dystonia, also known as Segawa disease. Clinical hallmarks comprise parkinsonian and other extrapyramidal symptoms. Biochemically the defect leads to the defective synthesis of catecholamines, in particular dopamine. The diagnosis relies on a characteristic pattern of biogenic amine metabolites exclusively in the CSF and can be confirmed by establishing a mutation in the TH gene. Here we present a patient meeting all diagnostic criteria, including a new homozygous mutation (926T > C) with confirmed parental heterozygosity, extrapyramidal symptoms, but atypical other symptoms with periodic neurological episodes observed every 4 days and unresponsive to dopa treatment. The CSF biochemical abnormalities were severe. Uncharacteristically, a strongly abnormal urinary catecholamine metabolite pattern was also consistently observed. The atypical presentation of this patient shows that the clinical and metabolic phenotype of TH deficiency is more variable than formerly thought, and that the condition should no longer be considered as a treatable disorder per se.- - - - - - - - - - ranking = 0.85714285714286keywords = deficiency (Clic here for more details about this article) |
10/104. 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 = 0.85714285714286keywords = deficiency (Clic here for more details about this article) |
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