Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a family of 4 siblings from a non-consanguineous marriage, presenting with an early onset recessive cerebellar ataxia and progressive distal limb wasting. Ocular or other telangiectasias were absent. There were neither frequent infections nor immunodeficiencies. The two youngest patients exhibited an incapacitating myoclonus which abated markedly after 20 years. Late onset diabetes was demonstrated in 3 patients. Hypogonadism was not a feature and there was a prolonged survival in the 4 patients. The oldest sibling died of a pancreatic adenocarcinoma. alpha-Fetoprotein was elevated with normal carcinoembryonic antigen values in three patients. Cytogenetic analysis and radioresistant DNA synthesis was compatible with the diagnosis of ataxia-telagiectasia. This family probably represents a rare variant of ataxia-telangiectasia.
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PMID:An early-onset recessive cerebellar disorder with distal amyotrophy and, in two patients, gross myoclonia: a probable ataxia telangiectasia variant. 778 63

We review the main features of human mitochondrial function and structure, and in particular mitochondrial transcription, translation, and replication cycles. Furthermore, some pecularities such as mitochondria's high polymorphism, the existence of mitochondrial pseudogenes, and the various considerations to take into account when studying mitochondrial diseases will also be mentioned. Mitochondrial syndromes mostly affecting the nervous system have, during the past few years, been associated with mitochondrial DNA (mt DNA) alterations such as deletions, duplications, mutations and depletions. We suggest a possible classification of mitochondrial diseases according to the kind of mt DNA mutations: structural mitochondrial gene mutation as in LHON (Leber's Hereditary Optic Neuropathy) and NARP (Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa) as well as some cases of Leigh's syndrome; transfer RNA and ribosomal RNA mitochondrial gene mutation as in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes) or MERRF (Myoclonic Epilepsy with Ragged Red Fibers) or deafness with aminoglycoside; structural with transfer RNA mitochondrial gene mutations as observed in large-scale deletions or duplications in Kearns-Sayre syndrome, Pearson's syndrome, diabetes mellitus with deafness, and CPEO (Chronic Progressive External Ophtalmoplegia). Depletions of the mt DNA may also be classified in this category. Even though mutations are generally maternally inherited, most of the deletions are sporadic. However, multiple deletions or depletions may be transmitted in a mendelan trait which suggests that nuclear gene products play a primary role in these processes. The relationship between a mutation and a particular phenotype is far from being fully understood. Gene dosage and energic threshold, which are tissue-specific, appear to be the best indicators. However, the recessive or dominant behavior of both the wild type or the mutated genome appears to play a significant role, which can be verified with in vitro studies.
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PMID:Mitochondrial DNA alterations and genetic diseases: a review. 799 80

We report a patient with mitochondrial encephalomyopathy presenting parkinsonism, as well as her brother who had ataxia but not parkinsonism. Both patients had myopathy, deafness, and insulin-dependent diabetes mellitus. The proband was a 55-year-old woman, who has developed progressive difficulty in walking and slowness of movement since 53 years of age, becoming bed-ridden at 55. Neurological examination revealed mental impairment, a masked face, Myerson's sign, vertical supranuclear ophthalmoplegia, and severe sensorineural deafness, hypokinesia, rigidospasticity, and weakness of the extremities. But tremor and cerebellar ataxia were absent. Her 48-year-old brother gradually developed weakness of the lower extremities and drunken gait over a few years. On neurologic examination, vertical supranuclear ophthalmoplegia, moderate sensorineural deafness, and cerebellar ataxia were present, but parkinsonism was absent. Three other siblings were reported to have died in early childhood. Cranial MR imaging showed cerebral atrophy and mild atrophy of the cerebellar vermis as well as mild periventricular hyperintensities in T2-weighted images in both patients. However, no infarcts were seen. Laboratory investigations revealed slightly elevated lactate and pyruvate levels in the proband and elevation of pyruvate in her brother. A biopsy specimen obtained from the quadriceps muscle showed ragged-red fibers with modified Gomori trichrome staining, and a decrease of complex I+III and complex II+III activity in the proband. Mitochondrial DNA (mtDNA) analysis using the polymerase chain reaction and restriction enzyme Apa I showed a point mutation in the tRNA(Leu)(UUR)) gene (an A to G transition at nucleotide 3243) in both patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mitochondrial encephalomyopathy associated with parkinsonism and a point mutation in the mitochondrial tRNA(Leu)(UUR)) gene]. 802 31

We report a 66-year-old man with progressive spinal paraplegia. He was well until June of 1991 when he had an onset of backache and right chest pain. On August 25, he lost sensation to void and he became unable to urinate. On the same day, he noted weakness in his legs which became progressively worse, and he was admitted to our hospital. Past medical history included diabetes mellitus which was found 3 years previously. He had upper gastrointestinal series 2 months before, which revealed a normal study. On admission, he was alert and general physical examination was unremarkable. Neurological examination revealed a mentally sound man with normal higher cerebral functions. Cranial nerves were also intact. He was unable to walk. No muscle atrophy was noted, but he had moderate to marked (2/5) weakness in both legs. No ataxia was noted in the upper extremities. Jaw jerk was normal, however, deep reflexes in the upper extremities were decreased, and absent in the lower extremities Babinski sign was present bilaterally. All sensory modalities were diminished below the Th 6 dermatome. No meningeal sign was present. Emergency myelography was performed on the day of admission, which revealed complete block from the Th4 to Th8 segments. CSF taken at that time was xanthochromic, positive Queckenstedt test containing 1,133 mg/dl of protein, 54 mg/dl of sugar and 1/3 microliters of lymphocyte. On August 31, laminectomy was performed from Th5 to Th7. The spinal bones in this area was very fragile and hemorrhagic. A soft yellowish vascular-rich tissue was surrounding the spinal cord in the epidural space. Despite surgery his weakness in legs worsened, and he became paraplegic by September 10th. He became somnolent with disorientation to time. In the subsequent course, he developed metabolic acidosis on September 26. On September 28, he became anuric and hypotensive. He expired later on that day.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A 66-year-old man with backache and progressive difficulty of gait]. 826 41

The frequency of cerebellar infarctions over two and a half years was 2.7% of the 1300 hospitalized patients over that period. Sixteen patients with cerebellar infarctions were studied by using clinical manifestations and magnetic resonance imaging (MRI). Ages ranged from 41-87 (mean 63.5) years; 13 were men and 3, women. Risk factors included: hypertension (50%), diabetes (44%), prior stroke (44%), cardiac disease (38%), and hyperlipidemia (19%). Common symptoms and signs were dizziness/vertigo (75%), unsteadiness (69%), dysarthria (69%), and nausea/vomiting (50%). Infarcts mainly involved the posterior inferior cerebellar artery (PICA) territory and tended to be associated with brainstem infarcts in 14 of the 16 patients. Most cerebellar infarctions had a benign course, especially the small ones. No mortality was noted in this series. The short-term outcome of the cerebellar infarctions seemed to depend on the size of the infarcts and the sites of the artery occlusion. It was concluded that diagnosis of cerebellar infarctions requires a high index of clinical suspicion, especially when patients present with a sudden onset of ataxia, dizziness/vertigo, nausea/vomiting and dysarthria; and that MRI is a useful tool for the detailed study of cerebellar infarctions and can elucidate associated brainstem infarcts.
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PMID:A clinical and MRI study of cerebellar infarctions. 829 26

Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Other neurological features subsequently emerged, and "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly accepted acronym. Here, we describe 4 further cases from 2 families, in whom there occurred previously unrecognized neurological features, central apnea and neurogenic upper airway collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic resonance images revealed striking brainstem atrophy affecting, in particular, the pons and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnormalities. These neurological and neuroradiological features, in conjunction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other previously reported neurological complications (including anosmia, ataxia, epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurodegenerative disorder with prominent optic atrophy and diabetes mellitus.
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PMID:Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy. 860 54

The onset of Friedreich ataxia (FA) was before 10 years of age in 36 out of 95 personally observed patients. We studied the clinical and laboratory findings of these childhood onset patients. Mean onset age +/- SD was 6.3 +/- 2.4 years. Gait and stance ataxia and lower limb areflexia were constant, dysmetria, dysarthria, Babinski sign, pes cavus, scoliosis and decreased vibration sense were present in the majority of patients. Higher occurrence of diabetes in childhood onset cases (25%) was the only statistical difference in comparison with later onset patients. Mean onset age of diabetes was 21.1 +/- 6.9 years and all patients required insulin. ECG was abnormal in 72% of the patients and echocardiographic evidence of hypertrophic cardiomyopathy was found in 43%. Linkage analysis, performed in 10 families, showed no recombination between the polymorphic markers of the 9q13-21.1 region and the disease locus with a peak lod score of 4.21 at a recombination fraction = 0.00.
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PMID:Childhood onset of Friedreich ataxia: a clinical and genetic study of 36 cases. 867 22

A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.
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PMID:Autosomal dominant cerebellar ataxia deafness and narcolepsy. 874 54

We studied cerebral oxygen and glucose metabolism as well as cerebral blood flow using positron emission tomography (PET) in a case with MELAS showing dementia, diabetes mellitus, ataxia and lactic acidosis without any signs of stroke. This case, confirmed to have a point mutation at position 3243 in the transfer RNA gene of mitochondrial DNA, developed a stroke-like episode 8 months after the PET study. Uncoupling was observed between cerebral oxygen metabolism and cerebral blood flow with reduced fractional oxygen extraction ratio, indicating "hyperemia", not ischemia. The "hyperemia" may be closely related to the malfunction of mitochondria in aerobic energy production. A drastic decrease in cerebral oxygen metabolism (CMRO2) was found globally in contrast to preserved cerebral glucose metabolism (CMRglu), resulting in a remarkable decrease in the metabolic ratio (CMRO2/CMRglu). The dissociation between cerebral glucose and oxygen metabolism may be characteristic of MELAS.
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PMID:Cerebral metabolism of oxygen and glucose in a patient with MELAS syndrome. 875 Jan 17

A rare point mutation at nucleotide position 8356 in the transfer RNA gene in mitochondrial DNA was found in a Japanese family. Our proband had migraine and dementia associated with lactic acidosis in addition to myoclonic epilepsy with ataxia and ragged-red fibres in a muscle biopsy specimen consistent with the clinical characteristics of myoclonic epilepsy with ragged-red fibres (MERRF). His mother, who had the same point mutation, also had migraine but without myoclonus or ataxia. His aunt, who had the same point mutation and migraine, developed diabetes mellitus, encephalomyopathy and several stroke-like episodes associated with lactic acidosis (MELAS). This is the third family with the rare mutation seen in American and Italian families. The mutation may not be specific to Caucasians, and is probably closely related to the MERRF/MELAS overlap syndrome.
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PMID:The T-C(8356) mitochondrial DNA mutation in a Japanese family. 880 15


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