Mitochondrial G8363A mutation presenting as cerebellar ataxia and lipomas in an Italian family.
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Adult↗
Biomedical subjects
A Federico
Publications and source records attributed to A Federico.
Acute inflammatory neuropathy in Charcot-Marie-Tooth disease.
The authors report an association between acute inflammatory neuropathy and previously undiagnosed Charcot-Marie-Tooth 1A disease in a 15-year-old girl. Sural nerve biopsy study showed hypertrophic neuropathy with endoneurial infiltrates of macrophages and lymphocytes. This association may be coincidental, but a particular susceptibility to damage of these peripheral nerves cannot be excluded. This report confirms the importance of pes cavus as a sign of long-standing sensorimotor neuropathy.
Action Potentials↗
Detection of beta-A4 amyloid and its precursor protein in the muscle of a patient with juvenile neuronal ceroid lipofuscinosis (Spielmeyer-Vogt-Sjögren).
Muscle biopsy tissue from a patient affected by the juvenile form of neuronal ceroid lipofuscinosis (NCL) was studied immunohistochemically using antibodies to beta-amyloid peptide and amyloid precursor protein. Positive reaction in muscle was specifically localized to autophagic vacuoles and blood vessel walls. Increased acid phosphatase reaction suggested enhanced lysosomal activity. We hypothesize that beta-amyloid is deposited in NCL muscle by a lysosomal mechanism similar to that proposed in other disorders involving beta-amyloid.
Adult↗
Neurological involvement and quadricuspid aortic valve in a patient with Ehlers-Danlos syndrome.
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Adolescent↗
Proton magnetic resonance spectroscopy of the brain in dementia.
Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progresson or effects of drug therapy.
Alzheimer Disease↗
Studies on mitochondrial pathogenesis of Rett syndrome: ultrastructural data from skin and muscle biopsies and mutational analysis at mtDNA nucleotides 10463 and 2835.
In order to verify the pathogenic role of mitochondria in Rett syndrome, the results are reported of skin and muscle biopsies in two RS patients, showing morphological ultrastructural abnormalities in mitochondrial number and size. The investigation on two recently described mtDNA mutations (at nt 10463 and 2835) (Lewis et al., 1995; Tang et al., 1997) gave contrasting results with respect to previously reported data. In particular, the first mutation has been found in seven subjects, five of whom were from two different control groups, while the second mutation has been not detected in any of the 26 patients and controls. Although these results present some signs of a morphological impairment of mitochondria, they do not support the hypothesis that the two mutations may have a primary role in the pathogenesis of the syndrome and indicate the need for further investigations on the role of mtDNA in the pathogenesis of the syndrome.
Adolescent↗
Cerebellar dysgenesis and mental retardation associated with a complex chromosome rearrangement.
Cerebellar hypoplasia, mild mental retardation, skeletal abnormalities, and ataxia were present in a 40 years old patient with a complex chromosome rearrangement (CCR). Chromosomes 2, 5, 16, and 17 were involved in the CCR. For the definition of the eight breakpoints leading to the rearrangement FISH with whole chromosomes paintings and specific telomeric probes was employed. Gene disruption, positional effect variegation, and sub-microscopic deletions are all possible causes for the abnormal phenotype observed in the patient.
Adult↗
The significance of alpha-glutathione S-transferase determination in patients with chronic liver diseases.
BACKGROUND: Alpha-glutathione S-transferases (alpha-GST) are the ''basic'' class of a large family of enzymes, ubiquitarly distributed in the cells, particularly in the hepatocytes. Their principal biological function is the detoxification of the cells by conjugating glutathione with various electrophiles and hydroperoxides. METHODS: We evaluated plasma alpha-GST in comparison to aminotransferase values (ALT) in 234 patients: 18 healthy volunteers, 51 chronic alcohol abusers with (22) or without (29) chronic liver damage and 165 with chronic HCV infection (32 ''apparently'' healthy carriers of HCV infection, 88 with a biopsy-proven chronic hepatitis (CH), 48 treated with interferon, 15 with well compensated and 12 with decompensated liver cirrhosis (LC) and 18 with hepatocellular carcinoma (HCC). Alpha-GST were determined on the venous blood samples after an overnight fast by Hepkit Alpha-Biotech (Biotrin International, Dublin, Ireland). RESULTS: Control values: <8 ng/ml (range 2.7-6.3). In alcoholics we found a constant increase in 31% of patients without liver disease, in which ALT levels proved constantly normal, and in 13.6% of cirrhotics, without significant correlation among plasma values of alpha-GST, gamma-GT or alcoholemia. In ''healthy'' HCV-carriers, HCV-RNA determination selected 21 subjects positive for viral replication, while 11 were negative. HCV-RNA negative subjects had constant normality of plasma alpha-GST values, while in those HCV-RNA positive alpha-GST increased in 57% of cases. In patients with HCV-related chronic liver disease, alpha-GST proved higher than normal in 80.6% patients with CH, in 40% well-compensated and in 8.3% decompensated cirrhotics and in 33.3% of patients with HCC. No statistically significant correlation was observed between alpha-GST and other liver tests in all groups studied. In patients treated with interferon (6 MU x 3/weekly of alpha-interferon) alpha-GST plasma values were significantly higher in relapsers with respect to responders or not to interferon treatment and during the treatment only in relapsers, while ALT returned to normal values, alpha-GST did not change and, in some cases, increased further. No significant correlation was observed between response to treatment, ALT, alpha-GST and HCV-RNA plasma levels in all groups of CH patients. CONCLUSIONS: Data indicate that in patients with chronic liver disease with different aetiologies, plasma alpha-GST determination may be useful for discovering a liver involvement also when ALT are normal. In patients with HCV-related CH, plasma alpha-GST values may be utilized as reliable markers in monitoring the response to interferon treatment.
Journal Article↗
Enhancement of doxorubicin content by the antitumor drug lonidamine in resistant Ehrlich ascites tumor cells through modulation of energy metabolism.
The effect of the antitumor drug lonidamine (LND) on respiration, aerobic glycolysis, adenylate pool, doxorubicin (DOX) uptake, and efflux in DOX-resistant and DOX-sensitive Ehrlich tumor cells was investigated. The results may be summarized as follows: 1) In both types of cells, LND inhibited both respiration and glycolysis in a dose-dependent manner and lowered the ATP concentration. The effect was more marked in cells incubated in glucose-free medium; 2) LND raised, to a remarkable extent, the intracellular content of DOX in resistant and sensitive cells respiring on endogenous substrates because of reduced ATP availability, whereas in glucose-supplemented medium, where both respiration and glycolysis contributed to ATP synthesis, the increase was lower; and 3) when LND was added to DOX-loaded cells, it failed to significantly inhibit DOX efflux because of time-dependent phenomena. These findings indicated that LND, a drug currently employed in tumor therapy, might also be useful in reducing or overcoming multidrug resistance (MDR) of those cells with a reduced ability to accumulate and retain antitumor drugs.
Adenine Nucleotides↗
Mosaicism for full mutation and normal-sized allele of the FMR1 gene: a new case.
The main mutation in fragile X patients is the expansion of the CGG repeat in the first exon of the FMR1 gene, associated with hypermethylation of the proximal CpG island. An increasing number of atypical cases have been reported showing the coexistence of full mutation and premutated or normal-sized alleles. These genotypes are more difficult to detect, and if a PCR strategy alone is adopted, they can be incorrectly identified. We report on a fragile X man with severe phenotype and mosaicism for full mutation and a (CGG)7 normal allele, the shortest fragment reported as yet in mosaics. This case of mosaicism, as other similar cases previously reported, suggests that the normal-length allele can derive from a deletion during the same early stage of development in which the full mutation expansion also arose.
Adult↗
Giant axonal neuropathy with subclinical involvement of the central nervous system: case report.
The case of a 17-year-old girl with slowly progressive sensory-motor neuropathy is described. Sural nerve biopsy showed abnormally enlarged exons filled with neurofilaments. Neurofilament accumulation was limited to the axons and was not found in other cells of the skin or peripheral nerve. The patient showed EEG and brain MRI abnormalities, but there was no clinical evidence of central nervous system involvement. Although these findings suggest an atypical attenuated form of giant axonal neuropathy, a new nosological entity cannot be excluded.
Adolescent↗
Vitamin E serum levels in Rett syndrome.
In order to study the role of vitamin E in the pathogenesis of Rett syndrome (RS), we analysed vitamin E serum levels in twenty-eight patients affected by this disorder. We found lower vitamin E serum levels in nine cases (32.1%). These results indicated that the oxidative free radical metabolism may be impaired in a significant percentage of Rett syndrome patients suggesting the need for further studies of tissue vitamin E in different brain regions.
Adolescent↗
Schnyder corneal crystalline dystrophy: description of a new family with evidence of abnormal lipid storage in skin fibroblasts.
Schnyder corneal crystalline dystrophy (SCCD) comprises corneal opacities often associated with precocious arcus senilis and genua valga. The metabolic defect seems to be related to abnormal lipid storage in the central part of the cornea, especially the anterior stroma, consisting mainly of nonesterified cholesterol. Plasma lipid levels are not always increased suggesting that the disease may be due to abnormal lipid metabolism limited to the cornea. We observed a family with typical SCCD, in 1 case associated with mental retardation and mild cerebellar hypoplasia. Results of serum lipid analysis of all patients were normal. Ultrastructural study of a skin biopsy specimen and fibroblast pellet showed membrane-bound spherical vacuoles containing lipid material. Cultured fibroblasts stained by filipin, a fluorescent probe that specifically binds unesterified cholesterol, showed abnormal cytoplasmic fluorescent material, suggesting abnormal cholesterol metabolism. The presence of neurological impairment, associated with SCCD in 1 of our cases, may be regarded as coincidental. Evidence of storage lipids in skin and cultured fibroblasts suggests that the disorder of intracellular cholesterol metabolism is not limited to the cornea and that skin biopsy may be a useful method to confirm the diagnosis.
Adult↗
Rare mononeuropathies of the upper limb in bodybuilders.
Clinical and electrophysiological findings of mononeuropathies of thoracodorsal, dorsoscapular, terminal branch of suprascapular, and medial pectoral nerves are reported in 4 bodybuilders. All athletes used anabolic steroids. After about 1 year partial improvement of symptoms was evident in 2 cases and complete recovery in the other 2. The data are discussed in the light of the few other existing reports and possible pathogenetic mechanisms.
Acute Disease↗
Requests for electromyography from general practitioners and specialists: critical evaluation.
In order to improve the quality of service and limit costs of a local electromyographic service, the requests for electromyographic (EMG) examination issued by general practitioners and specialists were critically evaluated. The diagnoses suspected by referring doctors were compared with medical history and clinical data to analyze (1) the utility of EMG for the final diagnosis and (2) the concordance with that of the neurophysiologist and with the EMG results. In 1994 and 1995, there were 3482 patients referred to the EMG service. Only patients undergoing EMG for the first time (2706 subjects) were considered. In 76.6% of cases, the referring doctor had indicated the suspected diagnosis in the request. This diagnosis was compatible with medical history, symptoms and the results of neurological examination in 57.6% of cases. In 77.2%, the neurophysiologist considered the EMG useful in confirming the clinical diagnosis. The suspected diagnosis was confirmed by the clinical diagnosis of the neurophysiologist and by the EMG results in 54.2% and 45.4% of cases, respectively. When the request was issued by neurosurgeons, neurologists, orthopedists, rheumatologists and physiatrists, the suspected diagnosis was more accurate; as a consequence the EMG was more correctly oriented than when the request was issued by other specialists or by general practitioners. It is recommended that neurological examination be a prerequisite for EMG requests issued by general practitioners.
Cost-Benefit Analysis↗
A case of ethambutol-induced optic neuropathy harbouring the primary mitochondrial LHON mutation at nt 11778.
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Ethambutol↗
Cerebrotendinous xanthomatosis: evidence of lipomatous hypertrophy of the atrial septum.
Premature atherosclerosis and cardiac complications have been reported among the systemic manifestations of cerebrotendinous xanthomatosis (CTX), a rare bile acid disorder with predominantly neurological features. In some cases, myocardial infarction has been the cause of sudden death. We examined nine CTX patients to determine whether they also had clinical or subclinical signs of cardiovascular disorders. In four of them, transthoracic echocardiography showed thickening of the interatrial septum compatible with lipomatous hypertrophy. The unexpected association of the two abnormalities is unlikely to be coincidental and suggests that careful cardiac examination should be considered, even in the absence of clinical manifestations.
Adult↗
Clinical and stabilometric monitoring in a case of cerebellar atrophy with vitamin E deficiency.
The authors describe a case of early onset ataxia with cerebellar atrophy and vitamin E deficiency, treated with alpha-tocopherol supplementation and physically rehabilitated by postural biofeedback. Clinical assessments, serum vitamin E levels and postural evaluation by means of a stabilometric platform continued for about 2 years and significant clinical improvement was recorded. Our study confirms that combined physical therapy and vitamin E supplementation may result in improvement of cerebellar function. Motor improvement is directly related to vitamin E serum levels, providing further confirmation that normal vitamin E levels are crucial for proper brain functions.
Adolescent↗