Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present report documents a family with three cases in two successive generations of pigmentary orthochromatic leukodystrophy (POLD). The clinical features of these cases and histochemical and ultrastructural investigations of two of the brains from successive generations are discussed. A review of the familial cases of POLD reported in the literature is also presented. Transmission of these cases was by a dominant inheritance. Onset of the clinical symptoms occurred at 42 to 54 years of age; duration of the disease was from 2-11 years, and death occurred at 45 to 57 years of age. Clinical manifestations of all three cases were severe headaches; bilateral pyramidal, pseudobulbar, cerebellar, and frontal release signs; gait disturbances; euphoria, or apathy; epileptic seizures; and dementia. The neuropathological pattern consists of slight cerebral atrophy, brownish discoloration of the cerebral white matter with demyelination and severe gliosis, sparing the sub-cortical U fibers; presence in the macrophages of lipid pigment granules that are sudanophilic, non metachromatic, and PAS and iron positive. The electron microscopic pattern of the lipid pigment in the macrophages is that of ceroid: electron-dense, membrane-bound intracytoplasmic lysosomes with curvilinear and/or fingerprint profiles.
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PMID:The dominant form of the pigmentary orthochromatic leukodystrophy. 172 27

An autopsy case of Nasu-Hakola's disease (membranous lipodystrophy) was reported. A 29-year-old Japanese woman whose younger sister had been affected with typical Nasu-Hakola's disease with skeletal and neuropsychiatric syndromes and membrano-cystic lesions in the bones developed forgetfulness and lack of initiative. The clinical features were characterized by diminished drive, apathy, euphoria, disturbance of attention, amnestic syndrome, and gait disturbance. The clinical course of her illness was 8 years. The neuropathologic examination revealed marked symmetrical gliosis of the cerebral white matter (sclerosing leukodystrophy) predominantly in the frontal and temporal lobes with slight or moderate demyelination (dissociation glio-myelinique) and widespread axonal changes such as fragmentation and spheroid in the white matter of the cerebral hemisphere, cerebellum, basal ganglia, and brain stem. The ultrastructure of spheroids showed neurofilamentous accumulation. We discussed the importance of axonal changes with regard to the pathogenesis and etiogenesis of the disease.
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PMID:Nasu-Hakola's disease (membranous lipodystrophy). A case report. 724 60

We report the case of a 40-year-old woman with Alexander disease. She experienced single seizure as 1-year-old, and became less active after that. Her academic records in elementary school were poor. However, she graduated from junior college and was later employed as a clerk for a short duration. Her parents, who lived with her noticed her apathy when she was 38, and gait disturbance soon after. At the age of 40, she was admitted to a hospital because of a fall and was referred to us. Brain magnetic resonance imaging (MRI) showed significant leukodystrophy with frontal predominance, and cervical MRI revealed mild cervical cord atrophy with dilated central canal. We performed genetic analysis and found the R79H variant of the gene encoding the glial fibrillary acidic protein. The patient was diagnosed with Alexander disease and suspedted juvenile-onset on the basis of the genetic analysis and MRI findings. Patients with juvenile Alexander disease have been previously reported to have variable survival, ranging from the early teens to the 20's and 30's. Our patient may suggest that natural history of this disease is more variable than previously thought.
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PMID:[A case of Alexander disease suspected juvenile-onset and exacerbating after long stationary state]. 2378 27

We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect. Macroscopically, the cerebral white matter showed a gelatinous texture in the centrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy. Combined linkage analysis and homozygosity mapping in two related families delineated critical intervals of approximately 29 Mb. The comparison of whole genome sequence data of one affected Standard Schnauzer to 221 control genomes revealed a single private homozygous protein changing variant in the critical intervals, TSEN54:c.371G>A or p.(Gly124Asp). TSEN54 encodes the tRNA splicing endonuclease subunit 54. In humans, several variants in TSEN54 were reported to cause different types of pontocerebellar hypoplasia. The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds. These results suggest that TSEN54:c.371G>A causes the leukodystrophy. The identification of a candidate causative variant enables genetic testing so that the unintentional breeding of affected Standard Schnauzers can be avoided in the future. Our findings extend the known genotype-phenotype correlation for TSEN54 variants.
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PMID:TSEN54 missense variant in Standard Schnauzers with leukodystrophy. 3158 37