1/36. A case of hereditary ceruloplasmin deficiency with iron deposition in the brain associated with chorea, dementia, diabetes mellitus and retinal pigmentation: administration of fresh-frozen human plasma.We report a familial case of hereditary ceruloplasmin deficiency (HCD) showing an A-G transition in intron 6 of the ceruloplasmin gene. Clinical features consisted of chorea, cerebellar ataxia, dementia, diabetes mellitus, retinal pigmentation and iron deposition in the liver and brain without copper overload in those organs. The patient's children and siblings had similar laboratory results, but did not show any neurological abnormalities. She was medicated for diabetes mellitus at 43 years of age, and neurological signs appeared when she was 52 years old. The laboratory findings were anemia, low concentrations of iron and copper in serum and of copper in urine. ceruloplasmin was not detected in the serum. The iron and copper contents in the liver were 3,580 and 10 microg/g wet tissue, respectively. MRI of the brain showed iron deposition in the basal ganglia, dentate nucleus and thalamus. This case did not show any abnormal increase in copper in the blood and urine following CuSO(4)5H(2)O oral overloading test. Following the intravenous administration of commercially available fresh-frozen human plasma (FFP) containing ceruloplasmin, the serum iron content increased for several hours due to ferroxidase activity of ceruloplasmin. In the liver, the iron content decreased more with the combined intravenous administration of FFP and deferoxamine than with FFP administration alone. Her neurological symptoms improved following repetitive FFP treatment.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
2/36. Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI of the brain and biochemical observations in a patient with 4-hydroxybutyric aciduria; a progressive neurometabolic disease.We report a five-year-old boy with 4-hydroxybutyric aciduria. The child presented with global developmental delay, severe hypotonia and myoclonic seizures. The urine 4-hydroxybutyric acid was 1038 times that of normal, and other organic acids related to its further metabolism were also increased. electroencephalography showed findings indicative of cerebral dysfunction. However, other neurophysiological studies were normal. Clinical improvement was observed after the administration of vigabatrin and dextromethorphan. magnetic resonance imaging of the brain revealed cerebellar vermin atrophy and subtle white matter changes in the cerebral hemispheres. fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomographic (FDG PET) scan of the brain showed a marked decrease in the cerebellar metabolism, probably related to atrophy of cerebellar vermis and secondary cerebellar deafferentation. FDG PET scan is found to be of value in the understanding and assessment of brain functional alterations. It may be useful in monitoring and optimizing treatment strategies of this rare disease.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
3/36. Irreversible brain creatine deficiency with elevated serum and urine creatine: a creatine transporter defect?Recent reports highlight the utility of in vivo magnetic resonance spectroscopy (MRS) techniques to recognize creatine deficiency syndromes affecting the central nervous system (CNS). Reported cases demonstrate partial reversibility of neurologic symptoms upon restoration of CNS creatine levels with the administration of oral creatine. We describe a patient with a brain creatine deficiency syndrome detected by proton MRS that differs from published reports. Metabolic screening revealed elevated creatine in the serum and urine, with normal levels of guanidino acetic acid. Unlike the case with other reported creatine deficiency syndromes, treatment with oral creatine monohydrate demonstrated no observable increase in brain creatine with proton MRS and no improvement in clinical symptoms. In this study, we report a novel brain creatine deficiency syndrome most likely representing a creatine transporter defect.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
4/36. Glutaric acidemia, type I, missed by newborn screening in an infant with dystonia following promethazine administration.We report a child initially diagnosed with promethazine-induced dystonia despite a lack of response to diphenhydramine therapy. On further evaluation, the child was diagnosed with glutaric acidemia, type I (GA-I), an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-coa dehydrogenase. The characteristic clinical feature of GA-I is an acute encephalopathic and neurologic crisis typically occurring during a catabolic state. Despite slow improvement, many patients do not fully recover from a neurologic crisis, and residual neurologic morbidity can be significant. Although newborn screening using tandem mass spectrometry is expected to enable presymptomatic diagnosis of GA-I, this patient was not detected by newborn screening with tandem mass spectrometry. Therefore, a high suspicion of GA-I must be maintained in the evaluation of childhood dystonia, even when newborn screening results are reportedly normal.- - - - - - - - - - ranking = 0.57142857142857keywords = administration (Clic here for more details about this article) |
5/36. The metabolism of 3alpha, 7alpha, 12alpha-trihydorxy-5beta-cholestan-26-oic acid in two siblings with cholestasis due to intrahepatic bile duct anomalies. An apparent inborn error of cholic acid synthesis.Studies were carried out in a family in which two children with cholestasis due to intrahepatic bile duct anomalies were shown to have increased amounts of the cholic acid precursor, 3alpha, 7alpha, 12alpha-trihydorxy-5beta-cholestan-26-oic acid (THCA). The metabolism of THCA was studied in one of these patients after an intravenous injection of (3H)THCA, and the cause of the increased amounts of THCA in this condition was found to be due to a metabolic defect in the conversion of this compound into cholic acid. A small amount of (3H)cholic acid was also identified after (3H)THCA administration, confirming that this metabolic defect was incomplete. Varanic acid (3alpha, 7alpha, 12alpha, 24xi-tetrahydorxy-5beta-cholestan-26-oic acid), a metabolite of THCA, could not be identified in either of these patients. By assuming that this compound would be conjugated and excreted if the metabolic block occurred after the formation of varanic acid, the defect in these patients appears to be due to a deficiency of a 24-hydroxylating enzyme system required to convert THCA into varanic acid. This condition appears to be transmitted in an autosomal recessive fashion, because the two affected patients were of opposite sex, and neither a normal sibling nor the two parents have increased amount of THCA in their bile.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
6/36. Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.BACKGROUND: dihydrolipoamide dehydrogenase (DLD) deficiency is a rare cause of primary lactic acidosis in infancy. MATERIAL AND methods: This article presents the results of biochemical and molecular analyses and metabolic response to treatment procedures in a 10-week old boy presenting with vomiting, progressive hypotonia, lactic acidosis (pH 7.04; BE - 20; B-lactate 6.6 mmol/l, controls <2.1; CSF-lactate 4.8 mmol/l, controls <2.0), increased levels of branched chain amino acids in blood, and increased urinary excretion of branched chain oxo-acids due to DLD deficiency. RESULTS: DLD activity was less than 5% of control values in lymphocytes, muscle mitochondria and fibroblasts. Western blot analysis in muscle tissue showed a decrease in the quantity of DLD protein to 40% in comparison to control. A high-fat, low-protein diet supplemented with MCT oils and sodium dichloroacetate resulted in normalization of lactate, amino acids and organic acids in body fluids, but there was no improvement in psychomotor development. Novel heterozygous mutations were found in the DLD gene: A1081G and G1123A. Both mutations affect the same region of the binding site for FAD. The G1123A mutation, resulting in the substitution of Glu 375 > Lys, breaks down the possible interaction of glutamic acid with neighboring lysine and causes electrostatic and steric repulsion, which is likely to destabilize structure in this part of the protein. In case of the A1081G mutation, resulting in substitution of Met 361 > Val, no important intermolecular interactions are broken and the reason for destabilization of the protein is not as clear. CONCLUSIONS: The prognosis for children with DLD deficiency is unfavorable, although long-term normalization of most metabolites in body fluids may be achieved with the proper diet and the administration of sodium dichloroacetate.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
7/36. Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency.Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D-3-hydroxy[3-14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity disorder. A continuous intravenous glucose infusion at 38 microlmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
8/36. Perioperative management of a child with very-long-chain acyl-coenzyme a dehydrogenase deficiency.Very-long-chain acyl-coenzyme a dehydrogenase deficiency is an inborn error of fatty acid metabolism. The clinical presentation of this disease in children is either a severe form with onset of symptoms in the first months of life, cardiomyopathy, metabolic acidosis, myopathy and a high mortality, or a less severe form manifesting mainly with hypoglycaemia. Perioperative fasting and (even emotional) stress can trigger metabolic decompensation through the altered metabolism of endogenous fatty acids resulting in hypoglycaemia, acute cardiac and hepatic dysfunction and rhabdomyolysis. We report the perioperative management of a 9-year-old boy suffering from the severe form of this disease who underwent circumcision. metabolism was kept stable in this child by using a glucose--electrolyte infusion throughout the perioperative period to avoid the biochemical consequences of fasting and a benzodiazepine--opioid technique combined with regional anaesthesia to minimize the stress response. Considering reports about a possible interference of propofol with fatty acid oxidation and to avoid the unnecessary administration of fatty acids, propofol should not be used in these patients.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
9/36. pyridoxine-dependent seizures: a case report and a critical review of the literature.pyridoxine-dependent seizures are a recognized, although rare, cause of intractable seizures in neonates. patients with this autosomal recessive disorder have recurrent seizures that are resistant to conventional anticonvulsants but respond dramatically to intravenous administration of pyridoxine. life-long supplementation with pyridoxine is required to prevent seizure recurrence. In the absence of a biological marker for the disease, clinical diagnosis is often delayed and severe neurological sequelae are common. Herein, we report on the clinical course of a neonate with pyridoxine-dependent seizures. Delayed normalization of the electroencephalogram and a normal developmental outcome (at 15 months of age) on a dose of 10 mg/kg pyridoxine are distinctive features of the present case. We also review recent clinical observations and neurochemical studies that have added to our knowledge of this disorder.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
10/36. Pituitary function in a man with congenital aromatase deficiency: effect of different doses of transdermal E2 on basal and stimulated pituitary hormones.To clarify the role of estrogen on male pituitary function, the effects of different doses of transdermal E2 on pituitary secretion were evaluated in a man with aromatase deficiency. The study protocol was divided into the following three phases: no E2 treatment (phase 1); 25 microg transdermal E2 twice weekly for 9 months (phase 2);12.5 microg transdermal E2 twice weekly for 9 months (phase 3). Pituitary function was studied in detail during each phase of the study protocol by measuring hormone levels in basal conditions and after dynamic testing (GnRH, insulin tolerance test, GHRH plus arginine, TRH, and corticotropin-releasing factor; tests). Basal and GnRH-stimulated gonadotropin levels resulted inversely related to E2 serum levels, according to the dosage of estrogen administered. Basal and stimulated GH, PRL, and TSH serum levels did not change during the protocol study. The secretory pituitary reserve of GH was clearly impaired. Basal and stimulated ACTH and cortisol serum levels were not modified by estrogen administration. This study demonstrated that in the human male E2 is required at pituitary level for normal functioning of gonadotropin feedback both in basal and stimulated conditions. In this patient GH deficiency seems to be an adult-onset event since he reached a tall stature. However, the finding of a severe impairment in GH response to potent provocative stimuli together with the insensitivity of GH/IGF-I axis to circulating estrogens strongly suggest a possible involvement of estrogens on both the development and maturation of the somatotrophic axis. Finally, the congenital lack of estrogen activity seems to be associated with a slightly impaired secretion of PRL and TSH, suggesting a possible role of estrogens on the pituitary secretion of these hormones in the human male.- - - - - - - - - - ranking = 0.14285714285714keywords = administration (Clic here for more details about this article) |
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