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Biomedical subjects

E Morava

Publications and source records attributed to E Morava.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial disease criteria: diagnostic applications in children.

BACKGROUND: Based on a previous prospective clinical and biochemical study, a consensus mitochondrial disease scoring system was established to facilitate the diagnosis in patients with a suspected mitochondrial disorder. OBJECTIVE: To evaluate the specificity of the diagnostic system, we applied the mitochondrial disease score in 61 children with a multisystem disease and a suspected oxidative phosphorylation disorder who underwent a muscle biopsy and were consecutively diagnosed with a genetic mutation. METHODS: We evaluated data of 44 children diagnosed with a disorder in oxidative phosphorylation, carrying a mutation in the mitochondrial or nuclear DNA. We compared them with 17 children who, based on the clinical and metabolic features, also had a muscle biopsy but were finally diagnosed with a nonmitochondrial multisystem disorder by further genetic analysis. RESULTS: All children with a genetically established diagnosis of a primary oxidative phosphorylation disorder had a mitochondrial disease score above 6 (probable mitochondrial disorder), and 73% of the children had a score above 8 (definite mitochondrial disorder) at evaluation of the muscle biopsy. In the nonmitochondrial multisystem disorder group, the score was significantly lower, and no patients reached a score comparable with a definite respiratory chain disorder. CONCLUSIONS: The mitochondrial disease criteria system has a high specificity to distinguish between mitochondrial and other multisystem disorders. The method could also be applied in children with a suspected mitochondrial disorder, prior to performing a muscle biopsy.

Biopsy↗
PubMed2006

A scale to monitor progression and treatment of mitochondrial disease in children.

Mitochondrial diseases affect all age groups, but those with childhood onset often seem to experience the greatest burden of disability. In some paediatric patients this can be explained by a cumulative disability acquired over many years. In others, additional factors, including the nature and severity of the molecular defect, must be considered. To date, no large-scale studies have attempted to document the natural history of paediatric mitochondrial disease. This is in part at least, because no assessment tool has been available to plot the temporal course of a disease with such a diverse clinical spectrum. This paper describes how a practical and semi-quantitative rating scale has been devised for children with mitochondrial disease, the Newcastle paediatric mitochondrial disease scale (NPMDS). The scale is multi-dimensional and reproducible, offering a tool through which mitochondrial disease progression can be objectively monitored. We anticipate that use of this tool will facilitate both longitudinal natural history studies and the assessment of future therapeutic interventions.

Adolescent↗
PubMed2006

Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.

In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.

Adolescent↗
PubMed2006

Skeletal muscle ultrasonography in children with a dysfunction in the oxidative phosphorylation system.

OBJECTIVE: The aim of this prospective study was to investigate the diagnostic value of quantitative skeletal muscle ultrasonography in children suspected of having a mitochondrial disorder. METHODS: Muscle thickness and quantitatively determined echo intensity of four muscles were established in 53 children with symptoms indicative of a mitochondrial disorder. RESULTS: A sensitivity of 25 to 46 % was found, depending on the chosen cut-off point (abnormal or borderline abnormal), with a specificity of 85 to 100 %. Except for one, all abnormal ultrasound scans were found in children over five years of age. Within the group of patients with a mitochondrial disorder, a significant correlation was found between muscle echo intensity and age (r = 0.38; p = 0.047). CONCLUSIONS: We conclude that skeletal muscle ultrasound can be of additional value in the diagnosis of children with suspected mitochondrial disorders, especially in children over five years of age. With its low sensitivity, it is not suitable for screening purposes. However, since all abnormal ultrasound scans were found in children with a mitochondrial disorder, and no significant correlation with the MDC score was found, muscle ultrasound can be used complementary to this scoring system to facilitate the decision-making in pursuing further invasive diagnostics.

Adolescent↗
PubMed2005

Biochemical characteristics and increased tetraglucoside excretion in patients with phosphorylase kinase deficiency.

Patients with glycogen storage disease type IXa present with infantile hepatomegaly and a specific growth pattern, and variable biochemical alterations in blood. We studied the clinical and biochemical characteristics including the urinary oligosaccharide excretion of seven unrelated children. The urinary tetraglucoside excretion was increased in four children, three of whom had persistently high cholesterol and triglyceride concentrations. We propose screening for urine tetraglucoside excretion and the measurement of serum cholesterol in patients with growth delay and/or hepatomegaly to assess a possible glycogenosis.

1-Propanol↗
PubMed2005

Mitochondrial dysfunction in a patient with Joubert syndrome.

Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.

Abnormalities, Multiple↗
PubMed2004

Trisomy 1q43 syndrome: a consistent phenotype with macrocephaly, characteristic face, developmental delay and cardiac anomalies.

Trisomy 1q43 syndrome: a consistent phenotype with macrocephaly, characteristic face, developmental delay and cardiac anomalies: Patients with trisomy (1)(q42-qter) present with psychomotor retardation, macrocephaly, occasional presence of facial capillary naevi, cardio-vascular anomalies and small size for gestational age. We report on a girl with the same pattern of malformations, who has pure trisomy 1 q43: duplication of the region (1) (q43) and the translocation of the terminal region of the other chromosome 1 to the derivative 1, narrowing down the critical region for the characteristic traits of severe developmental delay, macrocephaly and congenital cardiac malformations.

Atrophy↗
PubMed2003

Tall stature and progressive overweight in mitochondrial encephalopathy.

We describe two children carrying an inherited T899C mutation in the mitochondrial ATPase 6 gene with mild encephalopathy and normal postnatal growth followed by tall stature and obesity. No familial tall stature, endocrine anomaly or advanced skeletal age were present. Failure to thrive is a characteristic finding in most patients with a mitochondrial disease. Our observations suggest that children with encephalomyopathy, even in the presence of a significant clinical overgrowth, should be screened for a possible defect in oxidative phosphorylation.

Adolescent↗
PubMed2003

A girl with cutaneous hyperpigmentation, café au lait spots and ring chromosome 15 without significant deletion.

Ring chromosome 15 [r(15)] syndrome is characterised by specific facial features, café au lait spots, failure to thrive, mental retardation and typically with a terminal deletion of the long arm of chromosome 15. We report a 2.5 year old girl showing normal growth and development, large hyperpigmented skin changes showing hypopigmentated areas inside, multiple café au lait spots and premature graying-like hypopigmentation of scalp hair. She had a karyotype of r(15) in peripheral lymphocytes and fibroblasts. By FISH analysis the breakpoint was located distal to locus D15S936 (15q26.3) and within 300 kb of the end of the chromosome, indicating no deletion of functional genes on 15q. Hyperpigmentation and café au lait spots are rare signs in ring chromosome syndromes, but with r(15) syndrome, café au lait spots have been described in about 30% of patients and have been considered to result from the deletion of gene(s) on distal 15q. Based on the frequent observation of patchy hyperpigmentation with the r(15) syndrome, absent hyperpigmentation in cases of distal 15q deletion without a ring chromosome, and the telomeric breakpoint location in our patient indicating no significant deletion, we propose that the cutaneous hyperpigmentation and café au lait spots in our proband represent effects of the r(15) chromosome but are not caused by the deletion of specific gene(s) on distal 15q. Patchy skin hypopigmentation is a well known nonspecific sign in cytogenetic mosaicism which is commonly seen in ring syndrome.

Cafe-au-Lait Spots↗
PubMed2001

[Decreased bone mineral density as a risk factor in the development of spinal deformities in neurofibromatosis].

Neurofibromatosis-1 is a here-do-familiar disorder that is associated with a variety of skeletal anomalies, mostly with spinal deformities in 10-50% of the patients. Intraoperatively, a poor vertebral bone quality has been observed. Efforts have been made to identify factors preventing curve progression, to optimize operational planning and to explain the pathomechanism. As part of the preoperative evaluation, the authors used a dual X-ray absorptiometry to assess the bone mineral density of the lumbar spine in 12 non operated patients with neurofibromatosis-1, supplemented by laboratory blood/urine investigations. A significant decrease in bone mineral density of lumbar spine was measured. An inverse relation was suggested between the severity of scoliosis and the lumbar spine Z-scores. No pivotal alterations were identified in the laboratory measurements. The bony tissue abnormality observed intraoperatively in neurofibromatosis-1 patients may be described as a diminution of the axial bone mineral density. The evaluation of bone mineral density in the course of the preoperative planning is proposed in neurofibromatosis-1.

Absorptiometry, Photon↗
PubMed2001

[Kennedy disease in a patient with progressive speech disorder].

Kennedy disease is an adult onset neuromuscular disease characterized by slowly progressive proximal and bulbar muscle weakness. The disease associates with gynecomastia, adult onset infertility and sensory neuropathy, and caused by pathologic expansion of CAG repeats at the N-terminal region of the androgen-receptor gene at Xq11-q12. We report on a patient presenting with slowly progressive muscle weakness of the lower extremities, progressive dysartry and swallowing difficulties. The clinical symptoms were not fully specific for the disease. Moreover the family history was suggestive for an autosomal dominant trait meaning a diagnostic pitfall at the original examination. Finally the firm diagnosis of the Kennedy disease was established by a polimerase chain reaction based method.

Adult↗
PubMed2001

Distal deletion, del(2)(q33.3q33.3), in a patient with severe growth deficiency and minor anomalies.

We report on an 18-month-old boy with a 2q33.3 deletion. The clinical findings observed in the propositus included minor anomalies of face and distal limbs, intrauterine and postnatal growth retardation, microcephaly and, so far, moderate developmental delay. Conventional GTG banded chromosome analysis indicated a small deletion in distal 2q. Subsequent analysis by fluorescent in situ hybridization (FISH) using different probes allowed us to narrow down the deletion to most or all of segment 2q33.3. This case shows the importance of the application of different YAC probes for a precise determination of breakpoints in small interstitial deletions.

Abnormalities, Multiple↗
PubMed2001

[Vascular diseases, spina bifida and schizophrenia in a single family associated with the heterozygote mutation of the heat-sensitive variant of methylenetetrahydrofolate reductase].

Homozygous mutation of the thermolabile variant of methylene tetrahydrofolate reductase (MTHFR) may result in hyperhomocystinemia, leading to an increased risk for early cardiovascular disease, neural tube defects, and possibly major depression, schizophrenia. According to recent studies heterozygosity for the thermolabile variant of the MTHFR gene mutation is also more frequent in patients with thrombotic disease compared to that in the average population. We report on a family with different types of early vascular disease. In four consecutive generations MTHFR heterozygosity was detected: in the proband and in her mother, grandfather and daughter. Further conditions of the family members, possibly due to carrying the mutation, came to light by the pedigree analysis and examinations. The patient had pulmonary emboli at young age, her aunt died of spina bifida shortly after birth. The patient's mother suffers from schizophrenia and depression. The grandfather had pulmonary emboli, her sister with spina bifida occulta also carries the same mutation, as does her daughter who is sofar asymptomatic. In other asymptomatic members of the family no mutations were found. Unexpectedly, hyperhomocystinemia was detected in all heterozygote individuals. Our study demonstrates the necessity for folic acid therapy in mutation carriers to prevent early vascular events, depression and schizophrenia, and also to reduce the risk for neural tube defects in a preconception setting.

Adult↗
PubMed2001

Do health behaviour and psychosocial risk factors explain the European east-west gap in health status?

BACKGROUND: Mortality rates are much more favourable in Western European countries than in those of Eastern Europe. Health behaviour and psychosocial factors have been suggested to be important contributors to East-West differences in mortality and health status. METHODS: To compare reported health status as well as health behaviours and psychosocial factors which may be related to unequal health status in different parts of Europe, standardised postal surveys of representative populations samples were conducted in six Eastern and Western European areas. RESULTS: Higher mortality in the eastern populations was associated with more reported morbidity and generally more negative health ratings. Health behaviours and psychosocial factors were also more negative in the East. Multivariate analyses suggested that the East-West difference in health status may be partly explained by differences in health behaviours and psychosocial factors. CONCLUSION: Efforts to promote health in Eastern Europe should concentrate both on the promotion of healthier lifestyles and on improvement of social and economic conditions.

Adult↗
PubMed2001

East-west differences in reported preventive practices. A comparative study of six European areas of the WHO-CINDI programme.

BACKGROUND: Differences have been reported in life expectancy and mortality between Eastern and Western European countries. Also, disparities have been found among different European countries or populations concerning the implementation of preventive practices by health professionals. This study analysed the patterns of reported preventive practices in three Eastern European areas and three Western ones. METHODS: Health surveys were carried out in particular geographical area of six countries participating in the project (three Eastern European countries; Russia, Poland and Hungary and three Western European countries; Finland, Germany and Spain). All of them are partners in the WHO-CINDI (Countrywide Integration Non-communicable Diseases Intervention) Programme. Three preventive practices are analysed: reported blood pressure and blood cholesterol measurements and reported antismoking counseling during the last year. Data are presented separately for the general population and for people reporting specific chronic conditions (cardiovascular disease, respiratory disease and/or diabetes mellitus). RESULTS: Blood pressure measurement and antismoking counseling are more frequently reported to be carried out by primary health care physicians in the Eastern European areas while blood cholesterol measurement is more frequently reported in Western European countries. All these preventive activities are more frequently reported to be done among people with chronic conditions than in the population as a whole. CONCLUSIONS: Major differences have been found in reported preventive practices between Eastern and Western European countries. Great potential exists for chronic disease prevention among them.

Blood Pressure↗