Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c oxidase (COX) is a complex enzyme composed of 13 subunits, three of which are encoded by the mitochondrial DNA (mtDNA). The other 10 subunits are encoded by the nuclear DNA, synthesized in the cytoplasm, and transported into the mitochondria. The complexity of the enzyme and its dual genetic control explain the heterogeneity of clinical phenotypes associated with COX deficiency. There are two major syndromes, one characterized by muscle involvement (fatal infantile or benign infantile myopathy), the other dominated by brain disease (Leigh syndrome, myoclonic epilepsy with ragged red fibers, Menkes' disease). Partial defects of COX have been shown in muscle of patients with progressive external ophthalmoplegia, either alone (ocular myopathy) or as part of Kearns-Sayre syndrome. Biochemical studies have documented either muscle-specific or generalized defects of COX; COX deficiency is reversible in the benign infantile myopathy. Immunologically detectable protein may be normal (benign myopathy) or variably decreased (fatal myopathy, Leigh syndrome). The subunit pattern of COX is normal by immunoblot in patients with fatal myopathy and Leigh syndrome; a disproportionate decrease of subunit II was seen in a patient with myoclonic epilepsy with ragged red fibers. Availability of the three mtDNA genes and of complementary DNA probes for eight of the 10 nuclear DNA-encoded subunits makes it possible to investigate the different diseases at the molecular level. Large deletions of mtDNA have been found in patients with ocular myopathy and Kearns-Sayre syndrome: the deleted mtDNA appear to be transcribed but not translated, thus explaining the partial COX deficiency.
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PMID:Cytochrome c oxidase deficiency. 217 26

Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons.
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PMID:Clinical manifestation of mitochondrial diseases in children. 821 54

Neuroimage studies of thirty-eight infants and children with mitochondrial disorders were reviewed: 24 ultrasound (US), 21 computed tomography (CT), and 27 magnetic resonance image (MRI) examinations were analyzed. Patients included seventeen with Leigh syndrome, two with Kearns-Sayre syndrome (KSS), one with myoclonus, epilepsy, and ragged red fibers (MERRF), one with Alpers disease, five with Menkes disease, two with fatty acid metabolic defect, two with Rett syndrome, and eight with unspecified mitochondrial disorders. KSS and MERRF tended to occur in older children, whereas Leigh syndrome, Menkes disease, and Alpers disease occurred in infants and young children. The deep cerebral nuclei and the cerebral white matter were commonly involved in Leigh syndrome and KSS. Subdural hematomas or effusions with profound cerebral atrophy was found in Alpers disease and Menkes disease. Tortuosities of basilar, Willis circle, and cerebral vessels were also noted in Menkes disease. MRI and CT examinations of Rett syndrome, fatty acid metabolic defect, and most of the unspecified mitochondrial disorders were normal. Our results indicate that neuroimage studies have characteristic findings for specific mitochondrial syndromes.
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PMID:Neuroimage in infants and children with mitochondrial disorders. 893 6

The results of cranial magnetic resonance imaging in 76 children (aged 3 weeks--17 years) with neurometabolic or other neurodegenerative diseases are presented. The number of diagnosed diseases was 22. MR symptomatology of 11 of them is presented. The list of characteristic images includes metachromatic leukodystrophy, mucopolysaccharidoses, X-linked adrenoleukodystrophy, Leigh, Menkes and Pelizaeus-Merzbacher diseases, glutaric aciduria type I, Canavan disease, neuronal ceroid lipofuscinosis, Hallervorden-Spatz and Huntington diseases. The diagnosis of neurometabolic/neurodegenerative diseases cannot be based on MRI alone but in some of them (metachromatic leukodystrophy, adrenoleukodystrophy, Leigh and Menkes diseases, glutaric aciduria type I, Canavan and Hallervorden-Spatz diseases) MRI can strongly suggest the diagnosis.
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PMID:[MRI in the diagnosis of congenital white matter diseases and other neurodegenerative diseases]. 1178 4

Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
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PMID:Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency. 2840 71