Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pediatric cardiomyopathies are a heterogenous group of conditions of which dilated cardiomyopathies are the most common clinicomorphologic subtype. However, the etiology and pathogenesis of many cases of dilated cardiomyopathies remain unknown. We describe a series of 5 cases of a rare but clinically and histologically distinctive dilated cardiomyopathy that was uniformly lethal in early infancy. The 5 cases include 2 pairs of siblings. There was parental consanguinity in 1 of the 2 pairs of siblings. Death occurred in early infancy (range, 22-67 days; mean, 42 days) after a short history of general lethargy, decreased feeding, respiratory distress, or cyanosis. There was no specific birth or early neonatal problems. Autopsy revealed congestive cardiac failure and enlarged, dilated hearts with ventricular dilatation more pronounced than atrial dilatation, and endocardial fibroelastosis. Histology showed prominent hypertrophic nuclear changes of cardiac myofibers and markedly increased myocyte mitotic activity including occasional atypical mitoses. Immunohistochemical staining for Mib1 showed a markedly increased proliferative index of 10% to 20%. Ancillary investigations, including molecular studies, did not reveal a primary cause for the cardiomyopathies. This distinctive dilated cardiomyopathy characterized by unusual histologic features of myocyte nuclear hypertrophy and marked mitotic activity is lethal in early infancy. Its occurrence in 2 pairs of siblings suggests familial inheritance. Although the underlying molecular pathogenesis remains to be elucidated, it is important to recognize this distinctive entity for purposes of genetic counseling.
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PMID:Mitogenic cardiomyopathy: a lethal neonatal familial dilated cardiomyopathy characterized by myocyte hyperplasia and proliferation. 2030 41

First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.
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PMID:Barth syndrome. 2339 19

A 4-year-old crossbred Quarterhorse mare was submitted to the Clemson Veterinary Diagnostic Center for necropsy examination with a chronic history of inappetence, weight loss and lethargy. Prior to death the horse had developed mild diarrhoea and began showing evidence of colic. Necropsy examination revealed a markedly enlarged heart due predominantly to marked dilation of the right atrium, tortuous congested mesenteric blood vessels, marked ascites, pleural effusion and pulmonary oedema. Further examination of the heart showed the endocardium of the left side of the heart, including the mitral valve leaflets, to be diffusely thickened. Microscopically, the endocardial thickening was due to deposition of fibrous connective tissue and elastin fibres. These findings are consistent with a diagnosis of endocardial fibroelastosis.
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PMID:Endocardial fibroelastosis in a quarterhorse mare. 2365 94