Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical course of a child with Krabbe's leukodystrophy was characterized by clinical seizures, startle myoclonus, and paroxysmal activity recorded by EEG. At autopsy in the fourth year, myelinated subcortical axons were destroyed, virtually completely. Despite isolation from major subcortical and interhemispheric connections, the cell and fiber pattern of the cortex appeared remarkably normal in routine histologic preparations. The normal range of pyramidal and stellate interneurons were also present in rapid Golgi impregnations. The dendritic arbors of pyramidal neurons appeared to be normally formed and were richly invested with spinous postsynaptic specializations. The near-normal morphology of neurons isolated in the neocortex by the myelinoclastic process illustrates the sustaining influence of local intracortical synaptic connections. Alterations of cortical neuronal circuits resulting from synaptic remodeling of local interneuronal connections may account for cortical hyperexcitability as seen in cases of leukodystrophy.
 ...
PMID:The isolated human cortex. A Golgi analysis of Krabbe's disease. 8 46

The author presents a four-year-old boy with Pelizaeus-Merzbacher disease who required anaesthesia during placement of PE (pressure equalization) tubes and a permanent silastic intravascular device (Broviac catheter). Pelizaeus-Merzbacher is one of a group of progressive, degenerative disorders of the cerebral white matter known as the leukodystrophies. They include metachromatic leukodystrophy, adrenoleukodystrophy, Krabbe's disease, Canavan's disease, Alexander's disease and Pelizaeus-Merzbacher disease. Due to the progressive nature of the disorders and their devastating effects on the central nervous system, these children frequently require anaesthesia during imaging procedures such as MRI or during various surgical procedures. Of concern to the anaesthetist is the high prevalence of seizure disorders, gastroesophageal reflux with the risk of aspiration, and airway complications related to poor pharyngeal muscle control and copious oral secretions. In addition, adrenal involvement and hypofunction may be seen in patients with adrenoleukodystrophy. Identification of these associated conditions during the preoperative examination will allow safe anaesthesia for these children.
 ...
PMID:Anaesthetic considerations for the child with leukodystrophy. 156 64

An 11-year-old girl was found to have severely reduced beta-galactocerebrosidase activity as evidence of late-onset globoid cell leukodystrophy, while her mother had almost normal enzyme activity in circulating white blood cells. Clinically, the patient showed a remitting course marked by seizures, ataxia, white-matter disease on computed tomographic scan, and reduced conduction velocities of peripheral nerves. Symptoms improved somewhat around the age of 10 years. Two sural nerve biopsies, performed 6 years apart, disclosed a demyelinating neuropathy. By electron microscopy, membrane-bound vacuolar lysosomes in Schwann cells of myelinated axons, unlike the typical needlelike inclusions seen in classic infantile globoid cell leukodystrophy, were present in both specimens. Thus, clinical, morphologic, and biochemical data in this patient--and her mother--emphasize, compared with past reports on late-onset globoid cell leukodystrophy, considerable variation in the nosologic spectrum of late-onset globoid cell leukodystrophy and conspicuous differences from classic infantile globoid cell leukodystrophy.
 ...
PMID:Late-onset globoid cell leukodystrophy: unusual ultrastructural pathology and subtotal beta-galactocerebrosidase deficiency. 217 71

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.
 ...
PMID:Late-onset Krabbe disease initially diagnosed as cerebroside sulfatase activator deficiency. 290 3

An 8-week-old boy presented with a history of irritability, progressive feeding difficulty, generalised weakness, tachypnoea, and minor motor seizures. The clinical course was characterised by rapidly progressive respiratory failure, and neurological deterioration culminating in death at age 15 weeks. Electron microscopical examination and histological studies of the lung showed the presence of numerous intra-alveolar and a few interstitial macrophages. Enzyme studies and subsequent histopathological studies on brain confirmed the diagnosis of an unusual variant of Krabbe globoid cell leucodystrophy.
 ...
PMID:Early infantile variant of Krabbe globoid cell leucodystrophy with lung involvement. 727 3

Early infantile Krabbe disease is a progressive neurodegenerative disease caused by deficiency of lysosomal enzyme galactocerebroside beta-galactosidase, with onset before the age of 6 months. We present serial clinical, radiological and neurophysiological findings of a patient with early infantile Krabbe disease, presenting at the third day of life with hypotonia, macrocephaly and neonatal seizures. The patient had a deceptively normal initial magnetic resonance imaging examination at the age of 3 months, with progression of the white matter disease over the following 9 months, showing a clinical picture of profound hypotonia with pyramidal and pseudobulbar signs, as well as mild optic atrophy. Assay of galactocerebroside beta-galactosidase activity in leukocyte culture disclosed a marked deficiency of the enzyme (0.00 nmol/mg protein per h with normal values > 0.7 nmol/mg protein per h), thus confirming the diagnosis of Krabbe disease. Nerve conduction velocity and evoked potential studies, as well as the electroencephalogram, were abnormal at the age of 6 months, while serial neurophysiological studies at the age of 12 and 18 months demonstrated the progressive nature of the disease.
 ...
PMID:Early infantile Krabbe disease: deceptively normal magnetic resonance imaging and serial neurophysiological studies. 940 97

Krabbe disease or globoid cell leukodystrophy (GLD) is an autosomal recessive disorder resulting from the defective lysosomal hydrolysis of specific galactolipids found primarily in myelin. This leads to severe neurological symptoms including seizures, hypotonia, blindness, and death, usually before 2 years of age in human patients. In addition to human patients, several animals, including dog, mouse, and monkey, have the same disease caused by a deficiency of galactocerebrosidase (GALC) activity. In this article we describe studies in cairn and West Highland white terriers (WHWT) affected with GLD. Through a screening test based on the molecular defect found in these breeds, over 50 cairn terrier carriers have been identified and a colony of five carrier dogs has been established. Affected dogs from this colony plus an affected WHWT were available for study. An affected WHWT was evaluated by magnetic resonance imaging at 6 and 11 months of age and pronounced changes in the T-2 weighted fast spin-echo images were found. Biochemical and pathological evaluation of the same dog after euthanasia at 12 months of age showed a large accumulation of psychosine in the brain and white matter filled with globoid cells. Some comparisons were made to younger affected and carrier dogs. Studies have shown successful transduction of cultured skin fibroblasts from an affected dog and normal canine bone marrow using a retroviral vector containing the human GALC cDNA. Successful treatment of this canine model will lead to studies in some humans with GLD.
 ...
PMID:Globoid cell leukodystrophy in cairn and West Highland white terriers. 998 21

A 2-year, 6-month-old Saudi male with infantile Krabbe's disease was studied with fluorine-18-labeled-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) scan. The patient presented with a gradual loss of developmental milestones, irritability, and crying. At the advanced stage of the disease, he developed tonic-clonic seizures and became a microcephalic, extremely irritable, blind, spastic quadriplegic child, with no deep tendon reflexes. Laboratory studies revealed normal blood chemistry, muscle enzymes, very long chain fatty acids, and acylcarnitines. No abnormal urinary organic acids were detected. The cerebrospinal fluid protein concentration was increased. Magnetic resonance imaging of the brain revealed mild brain atrophy and white matter disease mainly in the centrum semiovale. Electroretinography was normal; however, electroencephalography and visual-evoked potentials were abnormal. Peripheral nerve conduction studies documented a demyelinating neuropathic process. The FDG PET study of the brain demonstrated a marked decrease in the metabolism of the left cerebral cortex and no uptake in the caudate heads. Normal glucose uptake was observed in the thalami, lentiform nuclei, and cerebellum. The patient did not present for subsequent clinic visits and is presumed dead.
 ...
PMID:Clinical and cerebral FDG PET scan in a patient with Krabbe's disease. 1066 5

The purpose of this study is to explore and compare epileptic seizures and EEG evolution in the various types of genetic leukodystrophy (GL). The authors reviewed the medical records and analyzed 69 serial EEGs in 27 patients with GLs: 13 with late infantile metachromatic leukodystrophy, one with juvenile metachromatic leukodystrophy, one with globoid cell leukodystrophy, six with X-linked childhood adrenoleukodystrophy, one with neonatal adrenoleukodystrophy, four with classic Pelizaeus-Merzbacher disease (PMD), and 1 with connatal Pelizaeus-Merzbacher disease. The diagnoses were made by biochemical and molecular studies. Two or more EEG studies with both awake and sleep traces were recorded during the varying clinical stages for each patient. At the beginning of the GLs, the EEGs were normal or showed mild slowing of background activity. Clinical seizures, mainly of focal origin, with progressive slowing and paroxysmal discharges on EEGs, usually appeared during the later stages of metachromatic leukodystrophy, X-linked childhood adrenoleukodystrophy, and classic Pelizaeus-Merzbacher disease. However, intractable seizures, mainly generalized in nature, and more severe slowing and abundant paroxysmal discharges on EEGs, with commensurate neurologic deterioration, were observed during the earlier course of globoid cell leukodystrophy, neonatal adrenoleukodystrophy, and connatal Pelizaeus-Merzbacher disease. These results indicate that GLs involve not only white matter, but gray matter as well. In all types of GL, there is good correlation between the severity of EEG changes, the severity of the diseases, and the clinical state of the patient.
 ...
PMID:Epileptic seizures and electroencephalographic evolution in genetic leukodystrophies. 1129 Sep 36

We report three children, each of whom seemed to have a primary mitochondrial disorder at presentation but was eventually diagnosed with an extramitochondrial inherited metabolic disease. The first patient presented at 6 months with developmental delay. Magnetic resonance imaging showed an abnormal signal in the white matter, and magnetic resonance spectroscopy showed elevated lactate peaks. A muscle biopsy showed complex IV deficiency, but leukocyte measurement of galactosylceramide beta-galactosidase activity was markedly diminished, consistent with Krabbe's disease. The second patient presented at birth with seizures and later had developmental delays. There was brain atrophy on neuroimaging. Serum and cerebrospinal fluid lactate levels were elevated. She had persistently elevated urine thiosulfate, which was diagnostic for molybdenum cofactor deficiency. The third child presented at 2 months with seizures and hypotonia. Magnetic resonance imaging showed an abnormal signal in the basal ganglia and surrounding white matter, whereas magnetic resonance spectroscopy showed elevated lactate peaks. A brain biopsy was diagnostic for Alexander's disease. These cases and others in the literature suggest that lactic acid elevation in the central nervous system can be found in a number of extramitochondrial neurologic diseases. Such diseases would constitute a third category of lactic acidosis.
 ...
PMID:Lactic acid elevation in extramitochondrial childhood neurodegenerative diseases. 1157 6


1 2 3 Next >>