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)

One hundred and forty-seven out of 1,600 infants and children showed no detectable ABR. ABRs were evoked by clicks. As to hearing acuity, 121 out of 147 patients had sensorineural hearing loss and 19 had no hearing impairment of high frequency (3-4 kHz) and high sound intensity (85-90 dBnHL). Eight patients could not be diagnosed whether they had hearing impairment or not. Among 19 patients who did not have sensorineural hearing loss in those ranges described above, 5 patients had cerebral palsy with severe mental retardation, 4 had mitochondrial encephalomyopathy, 3 had degenerative disease of unknown etiology, 2 patients had Down syndrome, 1 was a low birth weight infant with respiratory distress syndrome, 1 was a neonate born to a diabetic mother, 1 experienced severe neonatal asphyxia, 1 patient had acute lymphoblastic leukemia and 1 infant was later confirmed as a healthy girl. Of these, four patients showed transiently negative response in ABR. Nine patients remained undiagnosed as to hearing because they were in deep coma, had profound brain damage, or died in early neonatal period. They had major neurological diseases: severe neonatal asphyxia, holoprocencephaly, microcephaly, degenerative diseases of the central nervous system of unknown origin, metachromatic leukodystrophy, trisomy of chromosome 18, anoxic encephalopathy, small for gestational age newborn with intracranial bleeding and posthemorrhagic hydrocephalus. When ABR cannot be recorded using high sound intensity clicks, it usually suggests presence of hearing impairment of high frequency range. However, there are patients who have no hearing impairment in those sounds.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical diagnoses of pediatric patients without detectable auditory brainstem response (ABR)]. 280 11

Clinical and biochemical findings in a male subject with progressive encephalopathy and peripheral neuropathy are presented. Early development was normal. At age 3.5 years, he had seizures associated with fever. Subsequently, there was progressive neurologic deterioration. A CT brain scan at age 4 years, 2 months demonstrated multiple areas of variable density in the white matter. There was mild slowing of nerve conduction velocities and a sural nerve biopsy revealed segmental demyelinative neuropathy. Metachromatic leukodystrophy was suspected, but arylsulfatase A activity in leukocytes and fibroblasts was in the normal range. The cerebroside sulfate loading test on intact cultured fibroblasts showed attenuated hydrolysis leading to a tentative diagnosis of cerebroside sulfatase activator deficiency. However, the attenuated response of proband fibroblasts was not normalized by supplementation with activator in a reproducible manner, and urine showed hyperexcretion rather than deficiency of activator. Ultimately, an assay for galactosylceramide beta-galactosidase activity established a deficiency of this enzyme leading to the diagnosis of late-onset Krabbe disease.
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PMID:Late-onset Krabbe disease initially diagnosed as cerebroside sulfatase activator deficiency. 290 3

Arylsulfatase (ASA) enzyme deficiency is associated with metachromatic leukodystrophy (MLD), which is a hereditary myelin metabolic disease. It has been proposed that in alcoholic subjects with abnormal ASA, the accumulation of sulfatides may lead to demyelinization and generalized cerebral atrophy. ASA may be diminished in subjects with alcoholic cirrhosis having encephalopathic manifestations. This idea has not been previously proposed. Leukocyte arylsulfatase A (ASA) activity was measured in 30 healthy male volunteers and 28 patients with alcohol-related cirrhosis. The patients were divided into two groups: patients with alcohol-related cirrhosis with hepatic encephalopathy history and patients with alcoholic cirrhosis without history of hepatic encephalopathy. Alcoholic cirrhotic patients with history of encephalopathy showed 58.21% (40.95 nmol/mg protein/h) less enzymatic activity than a control group (98.00 nmol/mg protein/h), whereas the group without history of encephalopathy showed an ASA value which was 38.2% (60.55 nmol/mg protein/h) less than the control group. The results suggest that the low ASA activity is a factor associated to the appearance of encephalopathy in patients with alcohol-related cirrhosis.
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PMID:Leukocyte arylsulfatase A activity in patients with alcohol-related cirrhosis. 1146 Aug 94

Adult-onset metachromatic leukodystrophy (MLD) often shows schizophrenia- or encephalopathy-like symptoms at an early stage, such as behavioural abnormalities, cognitive impairment, mood disorders and hallucinations. The authors report the case of an adult woman with MLD who had been given antipsychotic medication for schizophrenia. In the differential diagnosis, screening of auto-antibodies was important for ruling out other encephalopathies as she had a euthyroid Hashimoto thyroiditis. Diagnosis was based the results of MRI, nerve conduction velocity, sensory evoked potential, motor evoked potential, lysosomal enzyme activity and gene analysis studies. Brain MRI showed diffuse demyelination spreading from the deep white matter to subcortical area as high signals at the edges of these lesions in diffusion and apparent diffusion coefficient-map images with the U-fibres conserved. The authors diagnosed adult-onset MLD coexisting with euthyroid autoimmune Hashimoto thyroiditis.
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PMID:Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis. 2279 96

A 14-year-old boy with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease had a lifelong history of failure to thrive and gastrointestinal symptoms including vomiting, pain, and diarrhea, leading to progressive cachexia. At the age of 9 years, after an extensive workup, the diagnosis of Crohn disease was strongly suspected, and he underwent colonoscopy with multiple biopsies. At 11 years of age, vision change and poor balance lead to a diagnosis of leukodystrophy by magnetic resonance imaging. Investigations for metachromatic leukodystrophy, adrenal leukodystrophy, and globoid cell leukodystrophy were all negative. A diagnosis of MNGIE disease was suspected when he continued deteriorating with gastrointestinal symptoms, multiple neurologic deficits, and encephalopathy. Markedly diminished thymidine phosphorylase activity and increased thymidine plasma levels confirmed the diagnosis of MNGIE. At autopsy, megamitochondria were observed by light microscopy in submucosal and myenteric ganglion cells and in smooth muscle cells of muscularis mucosae and muscularis propria, along the entire gastrointestinal tract from the esophagus to the rectum. Megamitochondria in ganglion cells were also observed in a retrospective review of the endoscopic intestinal biopsies taken at age 9 and 13 years and in the appendectomy specimen obtained 1 month before his demise. This study corroborates the presence of megamitochondria in gastrointestinal ganglion cells in MNGIE disease, better illustrates their detailed morphology, and describes for the first time similar structures in the cytoplasm of gastrointestinal smooth muscle cells. Pathologists should be able to recognize these structures by light microscopy and be aware of their association with primary mitochondriopathies.
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PMID:Diagnosis of mitochondrial neurogastrointestinal encephalopathy disease in gastrointestinal biopsies. 2345 26

A 48-year-old male patient presented with personality changes and progressive memory loss over 2 years with initially suspected Hashimoto's encephalopathy. Strategy of diagnostic workup of early onset dementia included dementia from neurodegenerative, neuroinflammatory, metabolic/toxic, and psychiatric origin. The patient's neurological exam was normal. MRI revealed a leukencephalopathy, predominantly in the frontal periventricular white matter, without notable changes over 2 years. On neurophysiological examination, prolonged central conduction times and a sensorimotor polyneuropathy were noted. Neuropsychological impairment included disorientation in place and a reduced short time memory. Behavioral alterations were predominated by sudden mood changes and disinhibition. Cerebrospinal fluid was normal. Despite presence of thyroid autoantibodies, glucocorticosteroid treatment did not improve the dementia. A metachromatic leukodystrophy was diagnosed by decreased arylsulfatase-A activity in leucocytes/fibroblasts and identification of a compound heterozygous mutation in the ARSA gene: c.542T>G (exon 3) and the novel mutation c.1013T>C (exon 6). Pathogenic function was suggested by bioinformatic mutation search. In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene.
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PMID:Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene. 2689 Jul 52

Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used MEDLINE, EMBASE, and GOOGLE SCHOLAR to provide an extensive update about epidemiology, classifications, pathology, clinical findings, diagnostic tools, and treatments of leukodystrophies. Comprehensive evaluation of clinical findings, brain magnetic resonance imaging, and genetic studies play the key roles in the early diagnosis of individuals with leukodystrophies. No cure is available for most heritable white matter disorders but symptomatic treatments can significantly decrease the burden of events. New genetic methods and stem cell transplantation are also under investigation to further increase the quality and duration of life in affected population.Expert opinion: The improvements in molecular diagnostic tools allow us to identify the meticulous underlying etiology of leukodystrophies and result in higher diagnostic rates, new classifications of leukodystrophies based on genetic information, and replacement of symptomatic managements with more specific targeted therapies.Abbreviations: 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive.
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PMID:An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. 3182 48

This article discusses mimics of multiple sclerosis (MS). Excluded in this discussion are neuromyelitis optica and vasculitis, discussed in other articles in this journal. Covered entities include posterior reversible encephalopathy syndrome, reversible vasoconstriction syndrome, acute disseminated encephalomyelitis, Sussac's Syndrome, and chronic idiopathic demyelinating polyneuropathy. There are also multiple infectious entities that mimic MS including; progressive multi-focal leukoencephalopathy (PML), Toxoplasmosis, Tuberculosis, Herpes Simplex Virus, Cytomegalovirus, Varicella zoster virus, Epstein Barr virus, Cryptococcus and Human immunodeficiency virus. In addition, there are leukoencephalopathies that can present in adulthood including Adrenoleukodystrophy, Metachromatic leukodystrophy, Cerebral autosomal dominant idiopathic leukoencephalopathy, Leigh's and Alexanders disease that could be mistaken for MS.
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PMID:What Can Mimic Multiple Sclerosis? 3244 85