1/40. Severe late acute allograft rejection in a child after living-related auxiliary partial orthotopic liver transplantation for ornithine transcarbamylase deficiency.Auxiliary liver transplantation (ALT) is known to correct liver-based metabolic disorders. However, it remains unclear whether the presence of a native liver influences the long-term prognosis of ALT for metabolic diseases. We reported on a 4-yr-old girl who had undergone living-related auxiliary partial orthotopic liver transplantation (APOLT) for ornithine transcarbamylase deficiency and experienced severe late acute rejection 18 months after liver transplantation, during weaning of immunosuppressive agents. Results of histological analysis of the graft indicated very severe acute rejection (rejection activity index, 9/9), and computed tomography revealed graft liver atrophy. These observations suggest the possibility that severe rejection might occur in APOLT, especially during weaning of immunosuppression.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
2/40. D-2-hydroxyglutaric aciduria with cerebral, vascular, and muscular abnormalities in a 14-year-old boy.D-2-Hydroxyglutaric Aciduria is a rare metabolic disorder that can cause injury to the brain and other organs. This case report concerns a 14-year-old boy showing irritability and typical signs of pyloric stenosis early postnatally. From the age of 3 months he had epilepsy. He was mentally retarded, hypotonic with preserved reflexes, and dystonic. The features were dysmorphic with elongated head and high arched palate. cardiomegaly with aortic insufficiency was diagnosed. magnetic resonance imaging of the brain revealed atrophy, reduced periventricular white matter, and multiple bilateral aneurysms of the middle cerebral arteries. The boy died at the age of 14 years. autopsy confirmed the white-matter reduction of the cerebral hemispheres as well as the arterial aneurysms of the middle cerebral arteries. Lesions of a few leptomeningeal and cerebral microvessels and of the renal and pulmonary arteries were also found. There were bilateral infarcts of the kidneys and signs of cardiomyopathy with noncompensated left ventricular failure. Signs of myopathy were evident. The clinical and postmortem findings imply a disseminated mesenchymal process.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
3/40. Hyperpipecolic acidemia associated with hepatomegaly, mental retardation, optic nerve dysplasia and progressive neurological disease.A male infant with hyperpipecolic acidemia is described. To our knowledge this is only the second report of this disorder. As with the previous case, our patient's course was characterized by persistent hepatomegaly, severe mental retardation, progressive loss of developmental milestones and diminished visual acuity associated with nystagmus, abnormal discs and retinal changes. death occurred at 2 years of age, following a progressive loss of neurological function. Pipecolic acid was repeatedly present in the serum at a concentrattion of 4-5 mg %. Trace amounts of this compound were also detected in the urine. In addition, an adaption of the method of Piez et al. (1956) for the direct quantitation of pipecolic acid in serum was evaluated and found to be very useful for the biochemical diagnosis of this disorder.- - - - - - - - - - ranking = 0.35571960594404keywords = optic (Clic here for more details about this article) |
4/40. 3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) consists of early bilateral optic atrophy, later development of spasticity, extrapyramidal dysfunction and occasionally cognitive deficits, and urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. The presence of the disorder in an Iraqi-Jewish genetic isolate led to mapping of the OPA3 gene to chromosome 19q13.2-q13.3, followed by isolation of the gene itself. OPA3 consists of two exons and codes for a peptide of 179 amino acids. Iraqi-Jewish patients with type III MGA are homozygous for a splice site founder mutation in OPA3 (IVS1-1G>C) which abolishes mRNA expression in fibroblasts. Here we report a novel mutation in OPA3 (320-337del) in a Kurdish-Turkish patient with optic atrophy and 3-methylglutaconic and 3-methylglutaric aciduria, previously carrying the diagnosis of type IV MGA. We conclude that type III MGA occurs in patients of non-Iraqi-Jewish ancestry, and should be considered in patients with type IV MGA that have optic atrophy and ataxia.- - - - - - - - - - ranking = 3.266789704458keywords = atrophy, optic (Clic here for more details about this article) |
5/40. gyrate atrophy of the choroid and retina: clinical, ophthalmologic, and biochemical considerations.A case of gyrate atrophy of the choroid and retina associated with hyperornithinemia has been subjected to extensive clinical and biochemical investigation. The familial occurrence of the ocular disease and of abnormality of amino acid was unique to this 28-year-old male, being absent in parents and siblings. He presented with progressive visual loss, and was found to have cataracts and large areas of peripheral lacunar atrophy. Clinically there was no other abnormality. However, he was hyperuricemic and has an abnormal EEG. Despite otherwise normal biochemical indices of hepatic, renal, and muscle function; selective catheterization of an artery, the hepatic vein, the renal vein, and a deep forearm vein showed all of these circulatory beds to be producing ornithine according to arteriovenous difference measurements. cerebrospinal fluid and urine contained increased amounts of ornithine. Though electromyography was normal, the muscle biopsy was abnormal. Clinical tests including arginine loading, glucose tolerance testing, and other measurements of blood variables provided inferences as to the metabolic locus of the abnormality. The syndrome is a systemic multiorgan disorder in which the choroid and retina would appear to be target organs and the hyperornithinemia to be of, as yet, undetermined cause and pathogenic significance.- - - - - - - - - - ranking = 6keywords = atrophy (Clic here for more details about this article) |
6/40. carbamyl phosphate synthetase-1 deficiency discovered after valproic acid-induced coma.valproic acid induced coma is presented in an adult patient without a history of metabolic disease. Liver biopsy revealed a reduction in activity of carbamyl phosphate synthetase-I, an enzyme obligated for transformation of ammonia to urea in the urea cycle. After recovery CT scan follow-up showed marked cerebral atrophy which did not exist prior to the state of coma. risk factors are discussed.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
7/40. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: impaired catabolism of isoleucine presenting as neurodegenerative disease.We describe a further case of recently reported 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a disorder of isoleucine metabolism. The development of pronounced brain atrophy and symmetrical alterations of the basal ganglia were observed and the importance of specific enzymatic tests is emphasized, which should be performed if urinary metabolites suggest impaired catabolism of isoleucine.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
8/40. Glutaric aciduria type 1 an atypical presentation together with some observations upon treatment and the possible cause of cerebral damage.This report describes an infant diagnosed aged twenty-five months as having glutaric aciduria Type 1 (GA 1). Initial presentation was with isolated macrocephaly at four months of age. Severe hypertonia, and dystonia, within 24 hours of minor head injury occurred at nineteen months of age. Serial cranial imaging showed subdural fluid collections, and increasing underlying cerebral atrophy, mainly frontal and temporal. Confirmation of the clinical diagnosis required repeated blood and urine analysis by high performance liquid chromatography and gas chromatography/mass spectrometry; diagnosis was later confirmed enzymologically. Treatment with riboflavin, L-carnitine, vigabatrin and baclofen, produced some symptomatic relief; a low protein diet, nitrazepam and sodium valproate appeared of less obvious use. The rationale for these attempts at treatment is discussed. The possible role of quinolinic acid in the genesis of the fronto temporal and striatal atrophy is discussed and measurement of the quinolinate concentration in cerebrospinal fluid (CSF) of this case and age-related controls is presented.- - - - - - - - - - ranking = 2keywords = atrophy (Clic here for more details about this article) |
9/40. Neuropathological, biochemical and molecular findings in a glutaric acidemia type 1 cohort.Glutaric acidemia type 1 (GA-1) is an autosomal recessive disorder characterized by a deficiency of glutaryl-coa dehydrogenase (GCDH) activity. GA-1 is often associated with an acute encephalopathy between 6 and 18 months of age that causes striatal damage resulting in a severe dystonic movement disorder. Ten autopsy cases have been previously described. Our goal is to understand the disorder better so that treatments can be designed. Therefore, we present the neuropathological features of six additional cases (8 months-40 years), all North American aboriginals with the identical homozygous mutation. This cohort displays similar pathological characteristics to those previously described. Four had macroencephaly. All had striatal atrophy with severe loss of medium-sized neurons. We present several novel findings. This natural time course study allows us to conclude that neuron loss occurs shortly after the encephalopathical crisis and does not progress. In addition, we demonstrate mild loss of large striatal neurons, spongiform changes restricted to brainstem white matter and a mild lymphocytic infiltrate in the early stages. Reverse transcriptase-PCR to detect the GCDH mRNA revealed normal and truncated transcripts similar to those in fibroblasts. All brain regions demonstrated markedly elevated concentrations of GA (3770-21 200 nmol/g protein) and 3-OH-GA (280-740 nmol/g protein), with no evidence of striatal specificity or age dependency. The role of organic acids as toxic agents and as osmolytes is discussed. The pathogenesis of selective neuronal loss cannot be explained on the basis of regional genetic and/or metabolic differences. A suitable animal model for GA-1 is needed.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
10/40. Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature.Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
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