1/34. L-2-hydroxyglutaric aciduria: two Japanese adult cases in one family.We report two adult Japanese sisters with L-2-hydroxy-glutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. magnetic resonance imaging revealed typical subcortical white matter lesions in both cases and showed brainstem atrophy and thickness of the calvarium in the elder sister. L-2-Hydroxyglutaric acid levels were increased in urine, plasma, and cerebrospinal fluid. These cases suggest that organic acid analysis is necessary even in elderly patients who seem to have neurodegenerative disorders.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
2/34. Clinical and brain 18fluoro-2-deoxyglucose positron emission tomographic findings in ethylmalonic aciduria, a progressive neurometabolic disease.We report a 2-year-old boy with ethylmalonic aciduria and vasculopathy syndrome evaluated by 18fluoro-2-deoxyglucose positron emission tomographic (18FDG PET) brain scan, with intense uptake of 18FDG in the caudate nucleus and putamen bilaterally but with no morphological changes on magnetic resonance imaging (MRI). A repeat 18FDG PET brain scan 1 year later showed a significant bilateral decreased uptake of glucose in the putamen and the head of the caudate nucleus as well as a decreased uptake in the frontal lobes. On MRI, there was atrophy and watershed infarcts in the basal ganglia, explaining the loss of glucose uptake. These results reflect a selective vulnerability of the basal ganglia, their functional derangement, and ultimate degeneration.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
3/34. 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 = 2keywords = atrophy (Clic here for more details about this article) |
4/34. Glutaric aciduria type II: observations in seven patients with neonatal- and late-onset disease.The clinical, biochemical, and neuroradiologic findings and clinical follow-up of seven patients with glutaric aciduria type II are reported. Three phenotypes of the disease are encountered: neonatal-onset form with congenital anomalies (two patients) or without congenital anomalies (three patients) and late-onset form (two patients). The neonatal-onset form presents as an overwhelming illness, with severe hypoglycemia and metabolic acidosis leading to rapid death. Frequently it is associated with perinatal energy deprivation, a neonate with low birth weight and prematurity. The late-onset form presents with intermittent episodes of vomiting, hypoglycemia, and acidosis especially after meals rich in fat and/or proteins. All parents are consanguineous and have a first- or second-degree relationship. Initially, in the two phenotypes with neonatal onset and during crisis in the late-onset phenotype, routine laboratory evaluation showed severe metabolic acidosis, with an increased anion gap, hypoglycemia without ketonuria, and disturbed liver function tests. In the majority of patients with neonatal-onset forms, the kidneys, liver, and at times the spleen are enlarged with an increased echogenic pattern; however, no hepatic or renal cysts are detected. cardiomegaly is observed in most patients. The diagnosis can be easily and rapidly reached through tandem mass spectrometry study of the blood and can further be confirmed by gas chromatography/mass spectrometry analysis of the urine organic acids. In this report, the magnetic resonance imaging/computed tomography brain studies showed brain atrophy, white matter disease, and in one patient, fluid-filled cavities in the periventricular area and putamina. fluorine-18-labeled 2-fluoro-2-deoxyglucose positron emission tomographic (FDG PET) brain studies in two patients with late-onset disease showed slightly decreased activity in the cerebral cortex in one and in the caudate nuclei in the other. brain FDG PET scan and magnetic resonance spectroscopy were normal in one patient with neonatal-onset disease. All patients were treated with a diet low in fat and protein, oral riboflavin, and carnitine. The results were promising for the late-onset disease. Intravenous carnitine gave rewarding results in one patient with neonatal-onset disease.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
5/34. optic atrophy in association with cobalamin C (cblC) disease.PURPOSE: To report the association of optic atrophy with cobalamin C (cblC) disease. methods: Descriptive case reports on three patients, two of whom were siblings. RESULTS: All three patients with cblC disease exhibited bilateral optic atrophy with decreased visual acuity. Of the two siblings, the younger sister had received cobalamin supplements from birth and the mother had been given cobalamin supplements prenatally. CONCLUSION: These three cases confirm the association of optic atrophy with cblC disease. Early treatment with cobalamin supplements does not appear to prevent the development of optic atrophy.- - - - - - - - - - ranking = 164.3888709012keywords = optic atrophy, atrophy, optic (Clic here for more details about this article) |
6/34. D-glyceric aciduria in a six-month-old boy presenting with West syndrome and autistic behaviour.D-Glyceric aciduria is a disease with a very heterogeneous group of symptoms, with D-glyceric acid excretion as the chief common characteristic. Findings described in previous patients include progressive neurological impairment, hypotonia, seizures, failure to thrive and metabolic acidosis. However, there are also asymptomatic patients with mild neurological impairment. A six-month-old boy was admitted to our clinic with the complaints of dullness to his environment, seizures and autistic behaviour. EEG revealed multifocal generalized epileptic activity in a hypsarrhythmia pattern. Organic acid analysis (GC-MS) in urine revealed increased glyceric acid excretion. Analysis of the optical form of glyceric acid by a polarimetric method supported the diagnosis of D-glyceric aciduria. MRI showed white matter lesions with cerebral atrophy, particularly in the frontotemporal regions, and reversible abnormalities in the mesencephalon, thalami and globus pallidium resolving after fructose restriction in the diet. To our knowledge, this is the first case report of a patient with D-glyceric aciduria who presented with West syndrome and autistic behaviour in whom serial MRI findings are also defined.- - - - - - - - - - ranking = 1.1194267820634keywords = atrophy, optic (Clic here for more details about this article) |
7/34. gyrate atrophy of the choroid and retina with hyperornithinemia.A case of gyrate atrophy of the choroid and retina and hyperornithinemia in a 28-year-old man was subjected to extensive clinical and biochemical investigation. The familial occurrence of the ocular disease and of abnormality of amino acids was unique to this patient, being absent in parents and siblings. He presented with progressive visual loss, and had cataracts and large areas of peripheral lacumar atrophy. Clinically there was no other abnormality. However, he was hyperuricemic and had an abnormal electroencephalogram. 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 a muscle biopsy specimen 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 choriod 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) |
8/34. A new case of CDG-x with stereotyped dystonic hand movements and optic atrophy.We report the clinical findings and the diagnostic work-up of a 17-month-old girl with CDG-x. Predominant clinical signs were, besides psychomotor retardation and truncal hypotonia, stereotyped dystonic hand movements and ophthalmological abnormalities such as optic atrophy, nystagmus and strabismus. Other symptoms that are often found in patients with CDG were not present, such as seizures, microcephaly, cerebellar hypoplasia, dysmorphic features, hepatointestinal disease, coagulopathy or multiorgan involvement. isoelectric focusing (IEF) of the patient's serum showed a marked elevation of disialotransferrin, thus confirming an IEF type 1 pattern. A generalized glycosylation defect was confirmed also by IEF of a further glycoprotein (alpha1-antitrypsin), an increased carbohydrate deficient transferrin (CDT) serum concentration and an increased CDT/transferrin ratio. All known types of CDG-I, secondary glycosylation abnormalities and variants of amino acid sequence were excluded.- - - - - - - - - - ranking = 200.4860886265keywords = optic atrophy, atrophy, optic (Clic here for more details about this article) |
9/34. mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum.OBJECTIVE: Mevalonic aciduria as a result of mevalonate kinase deficiency is an inborn error of cholesterol biosynthesis characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Pathogenic mutations in the mevalonate kinase gene in both disorders have demonstrated a common genetic basis. Our aim was to describe the clinical picture of adolescent patients with mevalonate kinase deficiency and to expand the clinical and biochemical spectrum of mevalonate kinase deficiency, particularly with regard to HIDS. methods: We report the clinical history and biochemical findings of 3 patients with mevalonic aciduria. RESULTS: In 2 siblings with mevalonic aciduria, a 15-year-old girl and a 14-year-old boy, the phenotype shifted with age. Ataxia has become the predominant clinical manifestation, whereas the febrile attacks occur less frequently but as yet have not disappeared. Both of them show marked elevations of immunoglobulin d (IgD). Psychomotor development is retarded but not regressive. Short stature developed in both patients. Additional findings include the development of retinal dystrophy and cataracts in both of them. The third patient is a 6-year-old boy who presented at the age of 5 years with cerebellar ataxia and retinal dystrophy. He is different from all known patients with mevalonic aciduria because of the mild neurologic involvement and because he has never developed febrile crises. In addition, levels of IgD were repeatedly normal. CONCLUSION: The clinical and biochemical spectrum of patients with mevalonic aciduria is heterogeneous. Manifestations of the disease seem to be age dependent, as evident from this first report of adolescent patients. In patients who survive infancy, short stature, ataxia caused by cerebellar atrophy, and ocular involvement with retinal dystrophy become predominant findings. Recurrent febrile crises seem to diminish with increasing age and may not even be an obligatory finding. Elevation of IgD is most likely a secondary phenomenon that seems to be linked to recurrent febrile crises.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
10/34. Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I III and II III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
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