Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A young child with Hallervorden-Spatz syndrome is presented. She was well until 8 years of age when she lost interest in activities and her school performance declined. At age 11 years, she began having episodes of blepharospasm, accompanied by bilateral ptosis and occasional episodes of oculogyric crisis. By age 12 years, her motor coordination had declined and she began to exhibit evidence of dementia, dystonia, dysarthria, and tremor. Motor incoordination, dystonia, and tremor progressed until the patient was wheel-chair-bound. Multiple tests were performed, including metabolic studies, magnetic resonance imaging, bone marrow biopsy, and electron microscopy of the buffy coat. Both bone marrow and buffy coat revealed inclusions in the cytosomes which were granular and osmiophilic. To our knowledge, this is the third case report of inclusion bodies found in patients with manifestations of Hallervorden-Spatz syndrome. These findings suggest that obtaining a buffy coat and bone marrow biopsy may aid in the diagnosis of Hallervorden-Spatz syndrome and ultimately provide information regarding etiology.
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PMID:Osmiophilic deposits in cytosomes in Hallervorden-Spatz syndrome. 170 Jul 20

Few parkinsonian patients present with 'pure akinesia' or with severe akinesia accompanied by only mild rigidity, tremor and other manifestations such as ophthalmoplegia. Pathological examinations of such cases have rarely been conducted and have revealed findings compatible with progressive supranuclear palsy (PSP), pallido-nigro-luysian atrophy (PNLA) or Parkinson's disease. We report a parkinsonian patient whose main clinical feature was akinesia. A postmortem study of this patient showed findings corresponding to PNLA and PSP. Histochemical properties of the pallidal pigment granules were equivalent to those of Hallervorden-Spatz disease (HSD) and striatonigral degeneration. In addition to iron-positive pigment granules, spheroids, severe neuronal loss and gliosis in the globus pallidus and substantia nigra, formation of Alzheimer's neurofibrillary tangle (NFT) in the brainstem shares characteristics with PSP, adult onset HSD and PNLA. We suggest that the underlying pathology of 'pure' akinesia is most often situated in the globus pallidus substantia nigra and subthalamus (Luys), and that PSP, PNLA and adult onset HSD may constitute a spectrum of one disease.
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PMID:Pallido-nigro-luysian atrophy, progressive supranuclear palsy and adult onset Hallervorden-Spatz disease: a case of akinesia as a predominant feature of parkinsonism. 170 2

A 68-year-old male patient with Hallervorden-Spatz disease with autopsy findings is presented. He died 5 years after the occurrence of progressive rigidity, mask face, shuffling gait and tremor. Family history was negative. At autopsy, loss of neurons with gliosis in the globus pallidus and substantia nigra, large deposits of iron pigments and axonal spheroids in the same areas were found. So far as we know, this is the first case of Hallervorden-Spatz disease with autopsy findings reported in China.
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PMID:Sporadic late-onset Hallervorden-Spatz disease presenting as parkinsonism in a Chinese patient. 212 48

At the age of 6 years a patient developed disorders of character, intellectual deterioration, tremor, falls and epileptic seizures. This was followed by extrapyramidal and pyramidal disorders with a fatal outcome at age 21. There was no family history. Histopathology showed evidence of Hallervorden-Spatz disease, remarkable by the diffusion of spheroids into the central nervous system gray matter and by the presence of innumerable Lewy bodies in the substantia nigra and locus coeruleus. Similar findings have been reported in only 3 other cases of typical Hallervorden-Spatz disease. They suggest a preferential affection of monoaminergic neurons.
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PMID:[Hallervorden-Spatz disease with Lewy bodies]. 300 95

We studied a 68-year-old man who died after 13 years of progressive dementia, rigidity, bradykinesia, mild tremor, stooped posture, slow and shuffling gait, dystonia, blepharospasm, apraxia of eyelid opening, anarthria, aphonia, and incontinence. At autopsy, he had generalized brain atrophy with large deposits of iron pigment in the globus pallidus, caudate, and substantia nigra. Axonal spheroids were found in the globus pallidus, substantia nigra, medulla, and spinal cord. The neurochemical analysis of the brain revealed marked loss of dopamine in the nigral-striatal areas, with relative preservation of dopamine in the limbic areas. This is the oldest case of familial Hallervorden-Spatz disease reported and the first with neurochemical analysis of the brain.
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PMID:Late-onset Hallervorden-Spatz disease presenting as familial parkinsonism. 396 11

The interrelationships were studied between catecholaminergic and cholinergic systems in 169 patients with extrapyramidal system diseases: 68 patients with torsion dystonia (58 with the rigid form and 10 with the hyperkinetic form), 10 with Hallervorden-Spatz disease, 61 with hepatolenticular degeneration, and in 40 with idiopathic tremor. The secretion of dopamine (DA), noradrenaline (NA), adrenaline (A) and their precursor--DOPA) as well as the activity of acetylcholinesterase (AChe)--the enzyme disintegrating acetylcholine--were determined. In the rigid form of torsion dystonia and in Hallervorden-Spatz disease reduced secretion of all catecholamines (mainly DA) and DOPA was observed, with decreased AChE activity. In the hyperkinetic form of torsion dystonia the secretion of DA was increased and AChE activity was higher. In the patients with idiopathic tremor the secretion of A and NA was decreased and AChE activity was reduced. In patients with hepatolenticular degeneration the secretion of NA and DA was decreased and that of their immediate precursor DOPA was increased. Changes of AChE activity showed a wide range. The observed disturbances reflect various forms of disturbances in the equilibrium between the catecholaminergic and cholinergic systems which are one of the leading pathogenetic mechanisms in the development of various extrapyramidal syndromes.
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PMID:[Characteristics of central neurotransmitter metabolism in hereditary extrapyramidal disorders]. 732 5

We report the case of a 56-years-old woman patient, born to unrelated parents, who since 26-years-old gradually developed bradykinesia, rigidity, tremor of both hands, and speech and gait difficulties. Her past history was unremarkable. There was no family history of neurologic disease. She was admitted to our Hospital at age 39 and at that time she presented a full parkinsonian syndrome. The following tests were normal or negative: routine blood studies, serum copper, ceruloplasmin and cerebrospinal fluid examination. There was not Kayser-Fleicher ring, and fundoscopic examination revealed no abnormalities. Levodopa was introduced and response was good for more than ten years, despite early-onset of dyskinesias (three months after the introduction of the drug). After 30 years under levodopa she still presents a moderate response but with severe fluctuations of the motor performance. Except for slowness of cognition she developed no other neuropsychological impairments, and a recent neurological examination disclosed no abnormalities besides a parkinsonian syndrome. One year ago, a magnetic resonance imaging (MRI) was performed and showed bilateral, symmetrical lesions with "eye-of-the-tiger" pattern. This case illustrates the pathological heterogeneity of early-onset parkinsonism and suggests the possibility to find the typical MRI lesions seen in Hallervorden-Spatz disease in other degenerative affections involving globus pallidus.
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PMID:[Precocious Parkinson's disease associated with "eye-of-the-tiger" type pallidal lesions]. 748 42

We report a 20-year-old female with Hallervorden-Spatz syndrome (HSS). This patient is the product of consanguineous parents. She developed genu valgum, tendency to fall and mental deterioration at the age of 6, decrease of the number of spoken words at the age of 14, dysarthria, unsteady gait, postural tremor of the upper extremities, dystonic posture of hands and double incontinence at the age of 16. Her disease progressed slowly. Neurological examination on admission revealed severe mental retardation, optic atrophy, forced grasping, hyperactive tendon reflexes in the upper extremities and bilateral Babinski sign. An extensive laboratory investigation including the leukocyte lysosomal enzymes, serum amino acid analyses, copper studies and ceruloplasmin were almost within normal limits. MRI, T2 weighted images, showed markedly decreased signal intensity in the globus pallidus but substantia nigra and increased signal intensity in diffuse cerebral white matter. T1 weighted images showed marked atrophy of the brainstem and cerebellum. She met the diagnostic criteria for HSS by Swaiman; we diagnosed her as HSS group II. HSS is characterized by the presence of many spheroids in the central nervous system which is similar to neuroaxonal dystrophy (ND). However, clinical and pathological differences exist between HSS and ND, the precise classification of the two conditions has remained controversial. Although there are many reported cases in which both conditions overlap, this is the first reported case that simultaneously demonstrates increased iron deposition in the globus pallidus, marked atrophy of the brainstem and cerebellum and typical clinical course compatible with HSS.
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PMID:[A case of Hallervorden-Spatz syndrome with marked atrophy of the brainstem and cerebellum]. 836 59

We report a 75-year-old man with parkinsonism who died suddenly. The patient was well until 64 years of the age when he had an onset of tremor in his left hand. He was treated with a medicine in another hospital, and his tremor subsided. Five years after the onset, he started to note difficulty in fine finger movements and gait disturbance. He tended to lean backward with frequent falls. He was treated with bromocriptine, trihexyphenydil, and L-dops without apparent improvement. He visited our out patient clinic on November 11, 1993 when he was 75 years of the age. Neurologic examination at that time revealed an alert and well oriented man in no acute distress. Higher cerebral functions were intact. In the cranial nerves, he showed restriction in the upward as well as down ward gaze (40% of normal). He showed masking of the face and spoke in small voice. He walked in a stooped posture with small steps; retropulsion was present. Muscle rigidity was moderately positive in the neck, however, no rigidity was noted in the limbs. No abnormal involuntary movements were seen. He showed moderate bradykinesia and difficulty in finger tapping. Muscle stretch reflexes were normally elicited and the plantar response was flexor bilaterally. Sensation was intact. The autonomic nervous system appeared intact. He was treated with 300 mg/day of Sinemet with marginal improvement in his balance. In February 4, 1994, he had a common cold. On the next day, his parkinsonism worsened and he became unable to walk by himself. He was found unconscious in the bathroom on the same day. He was brought to our hospital by an ambulance. Upon arrival, he was unresponsive and was not breathing. Blood pressure could not be measured. Pupils were dilated without reaction to light. Cardiac resuscitation was attempted, however, ventricular fibrillation appeared on an EEG monitor, and he was pronounced dead at eleven o'clock in the morning. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had progressive supranuclear palsy because of vertical gaze palsy, axial rigidity, and poor response to levodopa. Regarding the cause of his sudden death, the chief discussant thought that he developed pulmonary embolism. Postmortem examination revealed non-bacterial thrombotic endocarditis in the heart, but this did not appeared to be related to his sudden death. Multiple disseminated small emboli were found occluding small arteries of the left lung; this was consistent with acute pulmonary embolism, and this was thought to be the cause of his sudden death. In the central nervous system, marked atrophy of the globus pallidus was noted; both internal as well as external segments showed marked atrophy; no myelinated fibers were seen in the globus pallidus. Neuronal cell loss was marked in the globus pallidus, the subthalamic nucleus, and the substantia nigra. No Lewy bodies or tangles were seen. The histologic diagnosis was consistent with pallido-nigro-luysian atrophy. Brownish pigments such as seen in Hallervorden-Spatz disease were seen in the globus pallidus. In addition, formy spheroids were seen in the substantia nigra. However, iron deposits were not so strong as to suggest Hallervorden-Spatz disease. Pallido-nigro-luysian atrophy is a rare neurodegenerative disorder. It is interesting to note that this condition may mimic progressive supranuclear palsy or pure akinesia clinically.
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PMID:[A 75-year-old man with parkinsonism and sudden death]. 853 59

Iron is a vitally important element in mammalian metabolism because of its unsurpassed versatility as a biologic catalyst. However, when not appropriately shielded or when present in excess, iron plays a key role in the formation of extremely toxic oxygen radicals, which ultimately cause peroxidative damage to vital cell structures. Organisms are equipped with specific proteins designed for iron acquisition, export, transport, and storage as well as with sophisticated mechanisms that maintain the intracellular labile iron pool at an appropriate level. These systems normally tightly control iron homeostasis but their failure can lead to iron deficiency or iron overload and their clinical consequences. This review describes several rare iron loading conditions caused by genetic defects in some of the proteins involved in iron metabolism. A dramatic decrease in the synthesis of the plasma iron transport protein, transferrin, leads to a massive accumulation of iron in nonhematopoietic tissues but virtually no iron is available for erythropoiesis. Humans and mice with hypotransferrinemia have a remarkably similar phenotype. Homozygous defects in a recently identified gene encoding transferrin receptor 2 lead to iron overload (hemochromatosis type 3) with symptoms similar to those seen in patients with HFE-associated hereditary hemochromatosis (hemochromatosis type 1). Transferrin receptor 2 is primarily expressed in the liver but it is unclear how mutant forms cause iron overload. Mutations in the gene encoding the iron exporter, ferroportin 1, cause iron overload characterized by iron accumulation in macrophages yet normal plasma iron levels. Plasma iron, together with dominant inheritance, discriminates iron overload due to ferroportin mutations (hemochromatosis type 4) from hemochromatosis type 1. Heme oxygenase 1 is essential for the catabolism of heme and in the recycling of hemoglobin iron in macrophages. Homozygous heme oxygenase 1 deletion in mice leads to a paradoxical accumulation of nonheme iron in macrophages, hepatocytes, and many other cells and is associated with low plasma iron levels, anemia, endothelial cell damage, and decreased resistance to oxidative stress. A similar phenotype occurred in a child with severe heme oxygenase 1 deficiency. Recently, a mutation in the L-subunit of ferritin has been described that causes the formation of aberrant L-ferritin with an altered C-terminus. Individuals with this mutation in one allele of L-ferritin have abnormal aggregates of ferritin and iron in the brain, primarily in the globus pallidus. Patients with this dominantly inherited late-onset disease present with symptoms of extrapyramidal dysfunction. Mice with a targeted disruption of a gene for iron regulatory protein 2 (IRP2), a translational repressor of ferritin, misregulate iron metabolism in the intestinal mucosa and the central nervous system. Significant amounts of ferritin and iron accumulate in white matter tracts and nuclei, and adult IRP2-deficient mice develop a movement disorder consisting of ataxia, bradykinesia, and tremor. Mutations in the frataxin gene are responsible for Friedreich ataxia, the most common of the inherited ataxias. Frataxin appears to regulate mitochondrial iron (or iron-sulfur cluster) export and the neurologic and cardiac manifestations of Friedreich ataxia are due to iron-mediated mitochondrial toxicity. Finally, patients with Hallervorden-Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2). The cardinal feature of this extrapyramidal disease is pathologic iron accumulation in the globus pallidus. The defect in PANK2 is predicted to cause the accumulation of cysteine, which binds iron and causes oxidative stress in the iron-rich globus pallidus.
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PMID:Rare causes of hereditary iron overload. 1238


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