Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CDG Ie is caused by a deficiency of dolichol-phosphate-mannose synthase 1 (DPM1), an enzyme involved in N-glycan assembly in the endoplasmic reticulum. Three proteins are known to be part of the synthase complex: DPM 1, DPM2 and DPM3. Only mutations in DPM1, the catalytic subunit, have been described in three families. One was homozygous for the c274C>G (R92G) mutation in DPM1 and two others were compound heterozygous for R92G and a c628delC deletion or a c331-343del13, respectively. Clinical features were a severe infantile encephalopathy, early intractable seizures, acquired microcephaly, and some dysmorphic features. We report a patient with milder symptoms: microcephaly, dysmorphic features, developmental delay, optic atrophy, and cerebellar dysfunction without cerebellar atrophy. The patient is homozygous for a new mutation in exon 9 of the DPM1 gene (c742T>C (S248P)). Our findings extend the spectrum of CDG Ie.
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PMID:Congenital disorder of glycosylation (CDG) type Ie. A new patient. 1566 74

L-2-hydroxyglutaric aciduria (L2HGA) is a chronic slowly progressive neurodegenerative disease characterized mainly by psychomotor developmental delay and cerebellar dysfunction. We report the clinical, biochemical, and neuroimaging features of 29 patients from 22 families. The mean age at the time of diagnosis was 13.4 years (2.5-32 years). The mean follow-up period of patients was four years (1.5-16 years). The main clinical findings were mental retardation and cerebellar involvement with ataxic gait and intentional tremor. Additional findings were mental retardation, macrocephaly and seizures. Diagnosis was confirmed by increased urinary excretion of L-2-hydroxyglutaric acid in all patients and highly specific magnetic resonance imaging (MRI) pattern showing subcortical leukoencephalopathy with bilateral high signal intensity in dentate nuclei and putamens. During the follow-up period, all patients had a static encephalopathy course. The underlying metabolic defect and the possible role of L-2-hydroxyglutaric acid are studied in a subgroup of these families and under evaluation for publication.
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PMID:L-2-hydroxyglutaric aciduria: a report of 29 patients. 1588 21

We present a 9-month-old male with acute rotavirus gastroenteritis who developed an acute encephalopathy with focal seizures and developmental regression. Magnetic resonance imaging showed bilateral striatal necrosis and raised glutarylcarnitine levels on tandem mass spectrometry of a (crisis) blood spot, and chromatography of organic acids revealed increased urinary excretion of dicarboxylic acid. Skin biopsy demonstrated a partial decrease in glutaryl-CoA dehydrogenase activity. The case was not typical for either rotavirus encephalitis/rotavirus-associated encephalopathy or for glutaric aciduria type I. The patient has developmental delay and continues to receive physiotherapy, speech therapy, and local developmental follow-up.
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PMID:Acute bilateral striatal necrosis with rotavirus gastroenteritis and inborn metabolic predisposition. 1593 90

D-2-hydroxyglutaric aciduria (D-2-HGA) is a very rare autosomal recessive metabolic disorder that has recently been associated with mutations in the D-2-hydroxyglutarate dehydrogenase gene. The biochemical phenotype of D-2-HGA is defined by the accumulation of abnormal amounts of D-2-hydroxyglutarate in cerebrospinal fluid, blood, and urine while the clinical phenotype can vary from a severe epileptic encephalopathy to normal. The basis for this phenotypic variation is not well-defined. We report a set of 412-year-old monozygotic (MZ) female twins with D-2-hydroxyglutaric aciduria who are shown to be compound heterozygotes for c.326-327dupTC, p.Glu110ArgfsX19, and c.1123G-->T, p.Asp375Tyr mutations in the D-2-hydroxyglutarate dehydrogenase gene, but who have remarkably different clinical phenotypes. One twin presented with multiple congenital anomalies, severe developmental delay, and abnormal neuroradiological findings, while the other had normal neurocognitive and neuroradiological phenotypes, without concomitant congenital abnormalities. Monozygosity of these twins implies that the differences in the clinical phenotype arise from postzygotic genetic changes, epigenetic differences, or environmental factors that influence the phenotypic response to biochemical perturbation rather than allelic or locus heterogeneity. Though the mechanistic role of these factors in D-2-HGA is far from apparent, the discordance in the phenotypes of these siblings establishes that these factors are at least as important as the nature of the mutant alleles in influencing the progression of the disorder.
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PMID:Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. 1608 10

Ethylmalonic encephalopathy is a rare metabolic disease presenting in infancy with developmental delay, acrocyanosis, petechiae, chronic diarrhea and early death. The biochemical characteristics of this autosomal recessive disease are urinary organic acid abnormalities. Recently it has been found to be caused by mutations in the ETHE1 gene, located on Ch19q13. Only about 30 patients have been reported, and we describe two additional cases. The first patient showed a typical clinical picture and biochemical abnormalities, with additional atypical clinical features. Neuroimaging studies showed extensive changes. A new homozygous mutation in exon 3 of the ETHE1 gene was found. The second patient was not investigated genetically; however besides the typical clinical picture and biochemical profile he was found to have cytochrome C oxidase deficiency.
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PMID:Ethylmalonic encephalopathy-report of two cases. 1637 14

We have identified a group of 13 patients with a homogeneous radiological pattern at MRI consisting of the molar tooth sign (MTS) and superior vermian dysplasia. The patients represent a relatively heterogeneous clinical group with variable severity of developmental delay, ataxia, hypotonia, and apnea. Careful examination of MRI prompted us to split our series of patients into two groups, based on IVth ventricle dilatation. In 4/13 patients the IVth ventricle was judged to be dilated and those patients were less severely affected while most clinically affected patients had a normal IVth ventricle. DNA samples of blood leukocytes from 6/13 consanguineous patients were genotyped using polymorphic markers encompassing the Joubert syndrome loci. We therefore sequenced AHI1 located in 6q23 in two patients who were homozygous at the locus and in four sporadic cases. Only one homozygous nonsense mutation was identified. Clinically, the patient exhibiting the AHI1 mutation was the most severely affected child with a profound encephalopathy, major hypotonia, ataxia, Leber congenital amaurosis, and normal IVth ventricle at the MRI. The present study suggests that the syndrome associating MTS and dysplasia of the superior vermis of the cerebellum is a clinically and genetically heterogeneous entity and that Jouberin (AHI1) mutations account for a marginal fraction of patients.
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PMID:Molar tooth sign and superior vermian dysplasia: a radiological, clinical, and genetic study. 1654 67

HIV-1 encephalopathy among perinatally infected children in the United States was initially defined by a classic triad of findings that included: (1) developmental delay, (2) secondary or acquired microcephaly, and (3) pyramidal tract neuromotor deficits. The most severe form of this disorder typically occurred among young children who developed rapidly progressive disease in concert with profound immunosuppression, and Pneumocystis jiroveci pneumonitis (PCP). The neuropathogenesis of this disorder appears to involve a cascade of viral products, various cytokines and chemokines, and neurotransmitters which promote ongoing inflammation, excitation, and overstimualtion of the N-methyl-D-aspartate type receptor (NMDAR) system. These subsequently lead to neuronal injury and death secondary to apoptosis or necrosis, astrocytosis, as well as dentritic and synaptic damage. The frequency of the most severe forms of encephalopathy among children has dropped dramatically since the introduction of highly active antiretroviral therapy (HAART). Of concern, however, is the possibility that a more insidious form of this disorder may be occurring presently among older vertically infected children as a result of inadequate penetration of HAART agents into the cerebrospinal fluid (CSF). This paper will review what published data there is as yet that bears on this question.
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PMID:HIV-1 encephalopathy among perinatally infected children: Neuropathogenesis and response to highly active antiretroviral therapy. 1706 Dec 85

During a 29-month period, 11 (12%) of 92 hospitalized patients with influenza B virus infection presented neurologic manifestations, which included febrile seizure in 4 cases and encephalopathy/encephalitis in 7 cases. Without appropriate antiviral therapy, recovery was uneventful in all but 1 patient, who had neurologic sequelae of quadriplegia and developmental delay.
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PMID:Neurologic manifestations in children with influenza B virus infection. 1707 38

We investigated two unrelated children with an isolated defect of mitochondrial complex III activity. The clinical picture was characterized by a progressive encephalopathy featuring early-onset developmental delay, spasticity, seizures, lactic acidosis, brain atrophy and MRI signal changes in the basal ganglia. Both children were compound heterozygotes for novel mutations in the human bc1 synthesis like (BCS1L) gene, which encodes an AAA mitochondrial protein putatively involved in both iron homeostasis and complex III assembly. The pathogenic role of the mutations was confirmed by complementation assays, using a DeltaBcs1 strain of Saccharomyces cerevisiae. By investigating complex III assembly and the structural features of the BCS1L gene product in skeletal muscle, cultured fibroblasts and lymphoblastoid cell lines from our patients, we have demonstrated, for the first time in a mammalian system, that a major function of BCS1L is to promote the maturation of complex III and, more specifically, the incorporation of the Rieske iron-sulfur protein into the nascent complex. Defective BCS1L leads to the formation of a catalytically inactive, structurally unstable complex III. We have also shown that BCS1L is contained within a high-molecular-weight supramolecular complex which is clearly distinct from complex III intermediates.
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PMID:Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy. 1740 14

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare disorder that results in long-chain fatty acids being unavailable for mitochondrial beta-oxidation and ketogenesis. It can present in the neonatal period or infancy with a severe clinical form, typically with convulsions, hypothermia, encephalopathy, cardiomyopathy and liver dysfunction, or with a milder phenotype with episodes of hypoglycaemia and hyperammonaemia during intercurrent illness. Investigations show hypoketonaemia, intermittent dicarboxyluria and hypocarnitinaemia with grossly elevated acylcarnitines. Enzyme assay or DNA analysis confirms the diagnosis. The severe phenotype results in severe disability or death. The less severe phenotype can also cause significant disability secondary to hypoglycaemia and/or hyperammonaemia at presentation. We report the outcome of two siblings with CACT deficiency. The index patient presented at the age of 2 months during a respiratory illness with hypoglycaemia, hyperammonaemia and cardiorespiratory collapse. Acylcarnitine profiles showed decreased free carnitine but striking elevations of long-chain acylcarnitines. Urine organic acids showed dicarboxylic aciduria. Fatty acid oxidation studies showed reduced oleate and myristate oxidation. His acylcarnitine profile normalized after he was started on a medium-chain triglyceride (MCT) low-fat diet and carnitine supplementation. Low CACT activity on enzyme assay confirmed the diagnosis. He has resulting profound developmental delay and epilepsy. The sibling was prospectively treated with a low-fat MCT diet and carnitine supplementation. Acylcarnitine profile at birth also showed elevated long-chain acylcarnitines. Fatty acid oxidation studies confirmed the diagnosis. To date he has normal development and has not had any significant periods of hypoglycaemia or hyperammonaemia.
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PMID:Prospective treatment in carnitine-acylcarnitine translocase deficiency. 1750 64


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