Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 41-year-old woman manifested a polyneuropathy, anasarca, pseudotumor cerebri, hyperhidrosis and hyperpigmentation of the skin, generalized lymphadenopathy, distal esophageal dysphagia, pleuritis, platelike pulmonary atelectasis, fluctuating renal insufficiency, hepatosplenomegaly, amenorrhea, and slight fever suggesting a connective-tissue disorder. Extensive clinical and laboratory evaluation did not support the initial impression of progressive systemic sclerosis or systemic lupus erythematosus but did show nonnecrotizing vascular changes, mild polyclonal gammopathy, and low thyroxin levels similar to the syndrome of polyneuropathy and endocrine disturbances recently reported from Japan. The impressive response to moderate-dose corticosteroids and exacerbation on withdrawal require diagnostic awareness of this insidiously progressive multisystem disorder. A bland vasculopathic process resulting from metabolic or immunologic disturbances appears to be the best explanation for this new syndrome, which has previously been recognized only in Japan.
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PMID:Polyneuropathy and anasarca: evidence for a new connective-tissue syndrome and vasculopathic contribution. 125 61

We report on a 12-year-old Chinese child with type C Niemann-Pick disease, who presented primarily with neurologic symptoms. He started to develop ataxia and dysarthria at the age of six years. Dementia, dysphagia, dystonia and seizures, in that sequence, followed within a couple of years. He was anarthric and bedridden five years after onset. Supranuclear vertical gaze palsy was found at the beginning of the illness. However, no hepatosplenomegaly or other physical abnormality was noted. Bone marrow aspirates revealed foamy storage cells and sea-blue histiocytes. However, sphingomyelinase activity in the cultured skin fibroblast was normal. The characteristic clinical presentations and typical pathologic and histochemical findings meet the diagnostic criteria of type C Niemann-Pick disease. We report the first Chinese case of type C Niemann-Pick disease and review 73 cases reported previously.
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PMID:Type C Niemann-Pick disease: report of a Chinese case. 790 66

A 26-year-old man presented with a 38 degrees C fever of undetermined origin in November 1977. His fever subsided in 1 month, but recurred concomitantly with dysphagia on December 10. For this reason, the patient visited our out patient clinic on December 15, and was hospitalized because a mass was found radiographically in the left lower lung field. A contrast-enhanced computed tomographic scan of the chest revealed an irregularly-shaped mass encircling the esophagus. Based on open-lung biopsy findings, the mass was diagnosed as non-Hodgkin's lymphoma, diffuse pleomorphic type. Neither swelling of the superficial lymph nodes nor hepatosplenomegaly was detected, and a bone-marrow aspiration specimen disclosed no atypical cells. Ga scintigraphy found accumulation only in this region, suggesting the posterior mediastinum as the origin of the lymphoma. Reports of non-Hodgkin's primary lymphoma in the posterior mediastinum are rare. Further, to our knowledge, there have been no reports at all on the diffuse pleomorphic type to date. This case was accordingly considered to be of highly informative value.
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PMID:[Posterior mediastinal diffuse pleomorphic lymphoma]. 1021 48

The clinical presentation and surgical and pathological findings of 46 children with unilateral tonsillar enlargement (UTE; age range 2 to 13 years, mean age 6.5) who underwent tonsillectomy for biopsy purposes between 1975 and 1995 were compared with those of 7 children who received treatment for tonsillar lymphoma (TL; age range 2 to 9 years, mean age 4.8) during the same period. There was no history of rapid tonsillar enlargement in children in the UTE group, and only 20 (43%) were symptomatic. Symptoms included recurrent sore throats in 10 patients (22%), snoring in 5 (11%), nasal obstruction in 4 (9%), and dysphagia in 1 (2%). No children had systemic symptoms or significant cervical lymphadenopathy. In contrast, tonsillar enlargement was observed to occur within a 6-week period in all children with TL, and 6 (86%) children had symptoms at presentation that included dysphagia in 5 (71%), snoring in 3 (43%), night sweats in 2 (29%), and fever and rigors in 2 (29%). Cervical lymphadenopathy greater than 3 cm was present in 6 (86%) children, while 1 child (14%) had hepatosplenomegaly. There was no histopathologic evidence of neoplasia in the UTE group, and a true discrepancy in size between the two tonsils was confirmed in only 21 of 44 (48%) cases. All 7 patients in the TL group had non-Hodgkin's lymphoma. All received chemotherapy, with 5 of the 7 cured and 2 dying of disease. The data suggest that tonsillectomy should be performed for biopsy purposes in UTE where there is a history of progressive enlargement, significant upper aerodigestive tract symptoms, systemic symptoms, suspicious appearance of the tonsil, cervical lymphadenopathy, or hepatosplenomegaly. The diagnosis of TL should also be considered when UTE is present in an immunocompromised child or one with a previous malignancy, when acute tonsillitis is asymmetric and unresponsive to medical treatment, or when rapid bilateral tonsil enlargement occurs. Observation is appropriate management for other cases of UTE.
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PMID:Unilateral tonsillar enlargement and tonsillar lymphoma in children. 1052 79

A neuronal storage disease affecting 5 captive Humboldt penguins is described. One bird died after 3 days of lethargy and anorexia. The 4 remaining birds died after a slowly progressing course of disease with signs that included lethargy, weakness, and neurologic dysfunction. Neurologic signs included dysphagia and ataxia. Gross lesions in the first animal to die consisted of hepatosplenomegaly indicative of avian malaria, which was confirmed histologically. The 4 remaining animals were mildly to moderately emaciated. Moderate to marked vacuolation of the neuronal perikarya was observed in Purkinje cells, neurons of the brainstem nuclei, and motorneurons of the spinal cord in all birds. By electron microscopy the vacuoles represented multilayered concentric lamellar structures. These findings were indicative of sphingolipidosis. All animals had been prophylactically treated for avian malaria, aspergillosis, and possible bacterial infections with chloroquine, itraconazole, and enrofloxacin. Circumstantial evidence implicates chloroquine therapy as the possible cause of the storage disease.
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PMID:Neuronal storage disease in a group of captive Humboldt penguins (Spheniscus humboldti). 1709 67

Niemann-Pick type C1 (NPC1) disease is an autosomal recessive disorder characterized clinically by neonatal jaundice, hepatosplenomegaly, vertical gaze palsy, ataxia, dystonia, and progressive neurodegeneration. The present study provides basic clinical and health information from the National Niemann-Pick C1 disease database that was obtained using a clinical questionnaire of 83 questions mailed to families affected by NPC1 disease living in the United States. The study was conducted over a 1-year period, during which time parents/caregivers and physicians completed the clinical questionnaire. Sixty-four percent (87/136) of the questionnaires were returned, with 53% and 47% representing male and female NPC1 patients, respectively. The average age of diagnosis for NPC1 disease was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years. The average age of death for NPC1 disease was 16.2 years, with one-half of patients dying before the age of 12.5 years. A common clinical symptom reported at birth was neonatal jaundice (52%), followed by enlargement of the spleen (36%) and liver (31%); ascites (19%) and neonatal hypotonia (6%) were much less frequent. With respect to developmental difficulties, the most common findings included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia (80%), and vertical gaze palsy (81%). Together, these findings confirm and extend previous reports investigating the clinical features associated with NPC1 disease.
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PMID:The National Niemann-Pick C1 disease database: report of clinical features and health problems. 1749 24

Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120,000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations.
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PMID:Niemann-Pick disease type C. 2052 56

We describe here a case of longstanding rheumatoid arthritis (RA) presenting with recurrent episodes of epigastric pain, melena, nonprogressive dysphagia, and hoarseness associated with persistent peripheral blood eosinophilia. Her RA was clinically inactive, but she had significant lymphadenopathy and hepatosplenomegaly. Computed tomographic scan of the thorax revealed circumferential wall thickening extending from the oropharynx to the gastroesophageal junction with a large polypoidal mass projecting into the lumen of the stomach. Histology revealed infiltration of the esophageal mucosa by eosinophils with a density of 40 to 80 per high-power field. The stratified squamous epithelium of the pharyngeal mucosa was also infiltrated by eosinophils with a density of more than 100 per high-power field. Eosinophilic esophagitis and pharyngitis were diagnosed, and the patient was administered corticosteroids and hydroxyurea, following which her symptoms resolved. On repeat imaging, there was significant reduction in esophageal wall thickening and luminal dilatation. There are few reports of tissue eosinophilia in association with RA, but the pathogenesis and any definite association with RA are not clear.
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PMID:Eosinophilic esophagitis and pharyngitis presenting as mass lesion in a patient with inactive rheumatoid arthritis. 2215 69

Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal lipid storage disease associated with impaired intracellular cholesterol trafficking. A wide spectrum of clinical phenotype has been described, with a possible onset at all ages of life from the neonatal period to adulthood, more often in childhood. Typically, hepatosplenomegaly, dystaxia, dysphagia, dysarthria and dementia are presented in NPC patients. Neurologic symptoms vary according to the onset age, but prolonged neonatal cholestasis, splenomegaly, cataplexy and vertical supranuclear gaze palsy are more specific signs to the diagnosis of the disease. Impaired cholesterol trafficking and unesterified cholesterol accumulation in the late endosomes and lysosomals, as a results of mutations in NPC1 or NPC2 genes, are initial for the disease, and defective cellular autophagy, defective lysosomal calcium homeostasis and oxidative stress may all play roles in the physiological processes. The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies or of pathogenic mutation of NPC1/NPC2 genes. Miglustat, the only available treatment approved to date, can alleviate neurological symptoms and slow disease progression when administered earlier.
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PMID:[Research advances in diagnosis and therapy of Niemann-Pick disease type C]. 2601 11

Sea-blue histiocytes in bone marrow can be associated with a number of conditions and have indeed often been reported in Niemann-Pick diseases, mostly in Niemann-Pick type B, but also Niemann-Pick type C. Rarely, it was reported to be related to a progressive neurological condition. In this work, early bone marrow aspirations in a boy following the discovery of hepatosplenomegaly at 1 month of age and later isolated splenomegaly did not reveal abnormal cells (which is not uncommon). Numerous sea-blue histiocytes were found in a repeated exam when the child was 10-year old, at a time he had developed a progressive neurological condition with frequent falls, clumsiness, slow and slurred speech, intellectual disability, dystonic movements, and dysphagia. Acquired sea-blue histiocytes should be considered initially on the basis of clinical symptoms. Whole-exome sequencing identified two variants in the NPC1 gene, leading to the diagnosis of Niemann-Pick type C1. This case points out the presence of sea-blue histiocytes in the bone marrow and has helped to reach a diagnosis of NPC1 which was very difficult to establish even after years of study. Given the rarity of this pathology and the variety of clinical presentations, it is important to communicate the possible forms of presentation of this syndrome.
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PMID:A progressive neurological condition with acquired sea-blue histiocytosis further the diagnosis of Niemann-Pick type C1 in a 10-year-old boy. 3231 43


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