Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the presence of mutations in the pantothenate kinase (PANK2) gene in a 27-year-old male Chinese patient with atypical pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Automated DNA sequence analyses revealed compound heterozygous mutations in the exon 3 and 5. This patient had a 10-year history of PKAN characterized by a slight tremor of the right hand when writing at onset and a slow progressive rigidity of the neck and the right arm and resting tremor in upper extremities. Dysarthria, dysphagia, and dystonic-athetoid movements of the face and right fingers were marked. Magnetic resonance showed the typical "eye-of-the-tiger" sign.
 ...
PMID:Novel compound heterozygous mutations in the PANK2 gene in a Chinese patient with atypical pantothenate kinase-associated neurodegeneration. 1574 60

We describe the case of an adult female with Hallervorden-Spatz disease (HSD), "eye-of-the-tiger" sign on cranial magnetic resonance imaging scan, and two mutations in the pantothenate kinase 2 (PANK2) gene. Symptomatic presentation included stuttering dysarthria, dystonic posturing, increased limb and axial muscle tone, choreoathetosis, stereotyped motor behaviors, and obsessive-compulsive symptomatology since adolescence. Extensive neuropsychological testing at 40 and 44 years of age revealed a relatively normal IQ and stable cognitive pattern overall. This case demonstrates that HSD patients who survive into middle age should not be assumed to have a progressive dementia. In such cases, atypical behavioral problems such as persistent obsessions and compulsions may be present instead.
 ...
PMID:Atypical Hallervorden-Spatz disease with preserved cognition and obtrusive obsessions and compulsions. 1583 58

Hallervorden and Spatz first described, in a sibship of 12, five sisters with clinically increasing dysarthria and progressive dementia, whose brains showed a brown discoloration of the globus pallidus and substantia nigra. Subsequently the basis has been shown to be a neurodegeneration with brain iron accumulation or pantothenate kinase-associated neurodegeneration due to mutations in the pantothenate kinase 2 (PANK2) gene. Progressive dystonia, Parkinsonism and dementia characterise the syndrome in children. The pathology comprises neuronal loss, axonal swelling, gliosis and iron deposits in the basal nuclei, disclosed by 'the eye of the tiger' sign on MR imaging. Since the criminal, unethical National Socialist activities of Hallervorden and Spatz came to light 'neurodegeneration with brain iron accumulation' has become the preferred nomenclature.
 ...
PMID:Neurodegeneration with brain iron accumulation: A cautionary tale. 1692 Dec 48

Hallervorden-Spatz syndrome is a rare autosomal recessive disorder that involves progressive extrapyramidal manifestations. Classical and atypical clinical presentations are known. Clinical details of patients admitted to the neurology ward or attending the movement disorder clinic of the All India Institute of Medical Sciences between January 2001 and July 2007 were reviewed. Sixteen patients (9 males and 7 females) were included in the study (median age 14 years; range 6-25). The most common clinical presentation was limb or cranial onset progressive dystonia. The patients with early onset had more frequent truncal and axial dystonia, including retrocollis, oromandibular-facial dystonia and chorea, dysarthria, pyramidal signs, gait disturbance, cognitive impairment, delay in milestones, retinitis pigmentosa, optic atrophy, oculomotor abnormalities, positive family history and acanthocytosis. Although rare, cerebellar ataxia, behavioural abnormalities, parkinsonism and apraxia of eyelid opening were exclusively seen in late onset patients. The present study highlights the heterogeneity of this disease entity and also describes certain unusual clinical features.
 ...
PMID:Clinical spectrum of Hallervorden-Spatz syndrome in India. 1905 77

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inborn error of metabolism characterized by iron accumulation in the basal ganglia and by the presence of dystonia, dysarthria, and retinal degeneration. Mutations in pantothenate kinase 2 (PANK2), the rate-limiting enzyme in mitochondrial coenzyme A biosynthesis, represent the most common genetic cause of this disorder. How mutations in this core metabolic enzyme give rise to such a broad clinical spectrum of pathology remains a mystery. To systematically explore its pathogenesis, we performed global metabolic profiling on plasma from a cohort of 14 genetically defined patients and 18 controls. Notably, lactate is elevated in PKAN patients, suggesting dysfunctional mitochondrial metabolism. As predicted, but never previously reported, pantothenate levels are higher in patients with premature stop mutations in PANK2. Global metabolic profiling and follow-up studies in patient-derived fibroblasts also reveal defects in bile acid conjugation and lipid metabolism, pathways that require coenzyme A. These findings raise a novel therapeutic hypothesis, namely, that dietary fats and bile acid supplements may hold potential as disease-modifying interventions. Our study illustrates the value of metabolic profiling as a tool for systematically exploring the biochemical basis of inherited metabolic diseases.
 ...
PMID:Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations. 2222 93

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration. The pathogenesis of this disorder is poorly understood and, although PANK2 is a mitochondrial protein, perturbations in mitochondrial bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN exhibits retinal degeneration and azoospermia, but lacks any neurological phenotype. The absence of a clinical phenotype has partially been explained by the different cellular localization of the human and murine PANK2 proteins. Here we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to its human orthologue. Moreover, we show that Pank2-defective neurons derived from KO mice have an altered mitochondrial membrane potential, a defect further corroborated by the observations of swollen mitochondria at the ultra-structural level and by the presence of defective respiration.
 ...
PMID:Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model. 2298 56

Authors describe clinical features, CT scan and MRI findings of 4 Egyptian boys (3 brothers from one sibship and a sporadic case) with Hallervorden-Spatz syndrome (HSS). These patients presented around the age of 10-years-old with rigidity, dystonia, dysarthria, mental deterioration with loss of previously acquired skills and choreoathetotic movements. The 3 brothers developed seizures around the age of 16 and the older brother died at the age of 20. Although, the CT scan of the 3 brothers showed bilateral symmetrical calcification of the basal ganglia, the MRI of the 4 cases demonstrated bilateral symmetrical hyperintense areas surrounded by hypointense areas in the globus pallidus giving the characteristic "eye-of-the-tiger" sign. Based on the clinical and MRI picture, these 4 cases could be the atypical type of HSS. However, calcification of globus pallidus is an associated finding in these cases. This is the second report in the literature with this association. In addition, we present the results of the use of antioxidants, L-dopa and Botulinum toxin injections in the management of these cases.
 ...
PMID:Hallervorden-Spatz syndrome. Variable imaging findings. 2337 30

Pantothenate kinase-associated neurodegeneration (PKAN) is the commonest, recessively inherited form of neurodegeneration with brain iron accumulation (NBIA) resulting from mutations in the pantothenate kinase 2 (PANK2) gene on chromosome 20. PKAN is usually rapidly progressive, presenting in the vast majority in the first decade of life (classic form). A rarer, later onset and slowly progressive (atypical) PKAN form also exists. We present two siblings of Cypriot descent, a 27-year-old man and his clinically asymptomatic younger sister, both of whom were found to be homozygous for a novel c.695A>G (p.Asp232Gly) missense mutation in exon 2 of the PANK2 gene. The index patient presented with a 5-year history of slowly progressive gait disturbance, dysarthria, mild axial rigidity and bradykinesia. His brain MRI scan revealed the characteristic "eye-of-the-tiger" sign. Atypical genetically confirmed PKAN cases are sparsely reported and should be considered in the differential diagnosis of patients presenting with a progressive extrapyramidal syndrome particularly if the radiographic findings are suggestive of iron accumulation. Effective treatment strategies for PKAN are not currently available and symptomatic therapy is often unsatisfactory. However, early diagnosis including the presymptomatic stage is important for genetic counseling and will be crucial for testing novel therapeutics in the future.
 ...
PMID:Novel homozygous PANK2 mutation causing atypical pantothenate kinase-associated neurodegeneration (PKAN) in a Cypriot family. 2465 37

Hallervorden-Spatz syndrome is a rare neurodegenerative disease of autosomal recessive inheritance which presents in childhood or early adulthood with dystonia, dysarthria, rigidity and choreoathetosis. Here we present an unusual case of atypical Hallervorden-Spatz syndrome with onset during adolescence and rapid progression in a young female patient who showed the characteristic "eye of the tiger" appearance on magnetic resonance imaging [MRI] of brain. This reporting intends to highlight Hallervorden-Spatz syndrome as a rare cause of extrapyramidal manifestations and the interesting radiologic picture of the disease.
...
PMID:Hallervorden-Spatz syndrome: a rare cause of extrapyramidal manifestations. 2520 40

Hallervorden-Spatz syndrome is a rare neurodegenerative disorder with hereditary properties. It usually occurs in young adolescents with extrapyramidal symptoms besides disturbed mental function. In this study, we present a 23-year-old neuropsychiatric patient who primarily misdiagnosed to have conversion disorder. She had 5-year history of progressive dysarthria and generalized abnormal movements. After detecting the pathognomonic sign of "eye of the tiger" diagnosis was confirmed. The patient was discharged. She had satisfactory condition in her follow-up. Such a rare syndrome should be considered in patients with similar presentation, and upon the diagnosis, PKAN2 gene study should be done to detect possible new mutations.
 ...
PMID:"Eye of the Tiger" in a Non-Responsive Neuropsychiatric Patient: A Case Report. 2943 99


<< Previous 1 2 3 Next >>