Gene/Protein Disease Symptom Drug Enzyme Compound
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 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on two siblings with hypotonia, ambiguous genitalia, microcephaly, ptosis, microretrognathia, thin lips, seizures, absent ossification of pubic rami, and brain abnormalities at the MRI. The two siblings died at 5 and 8 months, respectively. Molecular analysis indicated that SOX9, ARX, and DHCR7 genes were normal. Comparative genomic hybridization (CGH)-array analysis performed on the younger boy indicated two notable deletions, one on paternally inherited chromosome 4, and one on maternally inherited chromosome 5. The same deletions were found in a normal sister. Differential diagnoses and the possibility of a hitherto unreported syndrome are discussed.
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PMID:Ambiguous genitalia, microcephaly, seizures, bone malformations, and early death: a distinct MCA/MR syndrome. 2146 53

Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial diseases in children and adults. This study sequenced the exons and flanking intronic regions of the POLG gene from 2697 unrelated patients with clinical presentations suggestive of POLG deficiency. Informative mutations have been identified in 136 unrelated individuals (5%), including 92 patients with two recessive pathogenic alleles and three patients harbouring a dominant mutation. Twenty-four novel recessive mutations and a novel possible dominant mutation, p.Y951N, were identified. All missense mutations occurred at evolutionarily conserved amino acids within functionally important regions identified by molecular modelling analyses. Oligonucleotide array comparative genomic hybridisation analyses performed on DNA samples from 81 patients with one mutant POLG allele identified a large intragenic deletion in only one patient, suggesting that large deletions in POLG are rare. The 92 patients with two mutant alleles exhibited a broad spectrum of disease. Almost all patients in all age groups had some degree of neuropathy. Seizures, hepatopathy, and lactic acidaemia were predominant in younger patients. By comparison, patients who developed symptoms in adulthood had a higher percentage of myopathy, sensory ataxia, and chronic progressive external ophthalmoplegia (CPEO)/ptosis. In conclusion, POLG mutations account for a broad clinical spectrum of mitochondrial disorders. Sequence analysis of the POLG gene should be considered as a part of routine screening for mitochondrial disorders, even in the absence of apparent mitochondrial DNA abnormalities.
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PMID:Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. 2188 Aug 68

p-Synephrine is an adrenergic amine found in Citrus aurantium L. fruits and has been used for weight loss in dietary supplements. There are commercial products containing this substance associated to caffeine, salicin, and ephedrine. The aim of this study was to evaluate the acute toxicity of this mixture in mice of both sexes. The significative results observed after acute oral administration to male and female mice of 300, 350, and 400 mg/kg total of p-synephrine, ephedrine, salicin, plus caffeine in a 10:4:6:80 w/w ratio included a reduction in locomotor activity and ptosis in all treated groups for both sexes. Seizures were also observed in male (400 mg/kg) and female groups (350 and 400 mg/kg). Gasping and tearing were observed in males. Salivation (400 mg/kg), agitation (350 and 400 mg/kg), and piloerection (all treated groups) were significantly observed only in females. Deaths occurred in males at 350 and 400 mg/kg treated groups and the necropsy showed cardiopulmonary hemorrhage. A reduction in locomotor activity was confirmed through the spontaneous locomotor activity test, in which the number of crossings considerably decreased (P < .01) in all treated groups. The rotarod test showed a decrease in motor coordination at 400 mg/kg. Body temperature decreased significantly (P < .01) in all treated groups compared to controls. The results suggested clear signs of toxicity of p-synephrine, ephedrine, salicin, and caffeine association; this toxicity augments the attentiveness on commercial products containing this mixture, given the expressive number of adverse events related to its utilization.
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PMID:Toxicological effects of a mixture used in weight loss products: p-synephrine associated with ephedrine, salicin, and caffeine. 2240 69

The authors describe a newborn with postnatal myopathy who subsequently developed feeding difficulties, ophthalmoplegia, ptosis, encephalopathy, and seizures. She became ventilator dependent after sudden apnea. The myopathy was without ragged red fibers in the muscle biopsy. An electron transport chain study showed a markedly generalized low level of enzyme activity, particularly in complexes I, I + III, and IV. An initial electroencephalogram finding was normal; subsequent electroencephalograms showed suppression bursts. The mitochondrial copy number in skeletal muscle was 2% of normal.
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PMID:Mitochondrial depletion causes neonatal-onset leigh syndrome, myopathy, and renal tubulopathy. 2330 88

Introduction. Leptomeningeal carcinomatosis occurs in about 5% of cancer patients. Ocular involvement is a common clinical manifestation and often the presenting clinical feature. Materials and Methods. We report the case of a 52-year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis. Ocular symptoms were the presenting clinical feature in 34 patients (83%) out of 41 included in our review, the unique manifestation of meningeal carcinomatosis in 3 patients (7%). Visual loss was the presenting clinical manifestation in 17 patients (50%) and was the most common ocular symptom (70%). Other ocular signs were diplopia, ptosis, papilledema, anisocoria, exophthalmos, orbital pain, scotomas, hemianopsia, and nystagmus. Associated clinical symptoms were headache, altered consciousness, meningism, limb weakness, ataxia, dizziness, seizures, and other cranial nerves involvement. All patients except five underwent CSF examination which was normal in 1 patient, pleocytosis was found in 11 patients, increased protein levels were observed in 16 patients, and decreased glucose levels were found in 8 patients. Cytology was positive in 29 patients (76%). Conclusion. Meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms.
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PMID:Optic neuritis as isolated manifestation of leptomeningeal carcinomatosis: a case report and systematic review of ocular manifestations of neoplastic meningitis. 2422 6

Among the various forms of migraine headaches, ophthalmoplegic migraine is an uncommon and rare form, the incidence of which is approximately 0.7 per million. It presents predominantly with headache and ophthalmoplegia. One of more cranial nerves can be affected, however the third cranial nerve is most often affected. As a result, symptoms wise, mydriasis and ptosis are commonly seen. Patients generally recover completely within a few days or weeks, however residual deficits are known to occur in a minority of patients. One of the common generalised epilepsy syndromes is the juvenile myoclonic epilepsy (JME), its prevalence being roughly up to 10% of all patients with epilepsy. It usually begins in the second decade of life. Generalised tonic-clonic seizures myoclonic jerks absences constitute the main seizure types in JME. Studies indicate a definite association of epilepsy with migraine headaches and a significant number of migraneurs are found to be epileptic. Conversely, patients with epilepsy are two times more likely to have migraine, as compared to their first degree relatives without migraine. We report a known case of a female patient of JME having a history of classical migraine with aura presenting to us with headache and ophthalmoplegia. She was extensively evaluated to rule out other causes of isolated third cranial nerve palsy, with all the investigations being negative for any obvious cause. She was treated with non-steroidal anti-inflammatory drugs for the acute attack and was subsequently put on antimigraine medication, propranolol during her hospital stay, with which her ptosis recovered completely after 2 weeks. The patient was later started on tablet divalproex sodium, which the patient continues to take on a long-term basis, especially because of its efficacy as an antimigraine prophylaxis agent and a potent drug against JME.
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PMID:Ophthalmoplegic migraine with isolated third cranial nerve palsy in a known case of juvenile myoclonic epilepsy. 2429 72

Paranasal mucoceles are benign slow-growing paranasal sinus lesions, which usually develop following the obstruction of the sinus ostiu. They most frequently occur in the frontal sinus. Frontal mucoceles are expansive lesions usually causing visual clinical signs and symptoms such as diminution of vision, visual field defects, diplopia, orbital swelling, retroorbital pain, displacement of eye globe, ptosis, and proptosis. When the frontal mucocele extends intracranially, it can manifest with meningitis, meningoencephalitis, intracranial abscess, seizures, or cerebrospinal fluid fistula. Very rarely it can cause forehead swelling. We report an 80-year-old woman presenting with a forehead skin ulcer and painless subcutaneous forehead induration. Histopathologic examination revealed mucin deposition and inflammation. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans showed a mass originating from the frontal sinus with frontal bony defect and frontocutaneous fistula. Surgical excision of the mass confirmed the mucocele diagnosis. In this article, we present a case of frontocutaneous fistula and skin ulcer, which is an unexpected complication of frontal mucocele. We propose that in the case of a localized non-healing ulcerated forehead skin lesions, mucocele should be considered in the differential diagnosis.
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PMID:Unusual case of frontal mucocele presenting with forehead ulcer. 2541 50

Addition of the trinucleotide cytosine/cytosine/adenine (CCA) to the 3' end of transfer RNAs (tRNAs) is essential for translation and is catalyzed by the enzyme TRNT1 (tRNA nucleotidyl transferase), which functions in both the cytoplasm and mitochondria. Exome sequencing revealed TRNT1 mutations in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months. The second presented at 3.5 years with gait ataxia, dysarthria, gross motor regression, hypotonia, ptosis and ophthalmoplegia and had abnormal signals in brainstem and dentate nucleus. In subject 1, muscle biopsy showed combined oxidative phosphorylation (OXPHOS) defects, but there was no OXPHOS deficiency in fibroblasts from either subject, despite a 10-fold-reduction in TRNT1 protein levels in fibroblasts of the first subject. Furthermore, in normal controls, TRNT1 protein levels are 10-fold lower in muscle than in fibroblasts. High resolution northern blots of subject fibroblast RNA suggested incomplete CCA addition to the non-canonical mitochondrial tRNA(Ser(AGY)), but no obvious qualitative differences in other mitochondrial or cytoplasmic tRNAs. Complete knockdown of TRNT1 in patient fibroblasts rendered mitochondrial tRNA(Ser(AGY)) undetectable, and markedly reduced mitochondrial translation, except polypeptides lacking Ser(AGY) codons. These data suggest that the clinical phenotypes associated with TRNT1 mutations are largely due to impaired mitochondrial translation, resulting from defective CCA addition to mitochondrial tRNA(Ser(AGY)), and that the severity of this biochemical phenotype determines the severity and tissue distribution of clinical features.
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PMID:The 3' addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1. 2565 5

Non-syndromic, multi-organ mitochondrial disorders (MIDs) are frequently missed if treating physicians are not aware of them. We report a 85 years old Caucasian male, referred for tonic-clonic seizures, presenting with a plethora of abnormalities, including neurodermitis, atopic dermatitis, diabetes, hypertension, renal insufficiency, non-specific colitis, urine bladder lithiasis, bilateral cataracts, atrial fibrillation, diverticulosis, polyneuropathy, vitamin-D-deficiency, renal cysts, left anterior hemi-block, right bundle branch block, pulmonary artery hypertension, and heart failure. Neurological investigations revealed ptosis, quadriparesis, fasciculations, dysarthria, dysdiadochokinesia, tremor, hyperkinesia, ataxia, leukoencephalopathy, and basal ganglia calcification. Based upon this combination of abnormalities a non-syndromic mitochondrial multi-organ disorder syndrome (MIMODS, encephalo-myo-cardiomyopathy) was diagnosed.
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PMID:Multiorgan disorder syndrome (MODS) in an octagenarian suggests mitochondrial disorder. 2653 Feb 6

We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.
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PMID:Clinical delineation of the PACS1-related syndrome--Report on 19 patients. 2684 93


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