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Biomedical subjects

R C Sengers

Publications and source records attributed to R C Sengers.

At least 73 records · Page 4Linked to original sources
PubMed1991

In vitro contraction test for malignant hyperthermia in patients with unexplained recurrent rhabdomyolysis.

A few cases of non-anaesthetic-induced rhabdomyolysis in humans, predisposed to malignant hyperthermia (MH), have been described in literature. We studied a group of 6 consecutive patients with unexplained and recurrent attacks of rhabdomyolysis with the test used to determine susceptibility to MH, the in vitro contraction test (IVCT). The results of the IVCT showed 5 of these 6 patients to be MH susceptible. In cultured muscle cells from one of these patients a disturbed calcium homeostasis could be demonstrated. The relation between MH and recurrent rhabdomyolysis is discussed.

Adult↗
PubMed1991

Postnatal centralization of muscle fibre nuclei in centronuclear myopathy.

Postnatal centralization of muscle fibre nuclei, which were previously located subsarcolemmally, is described in a case of centronuclear myopathy (CNM) in a male patient with generalized muscle weakness since birth. A muscle biopsy was taken at the age of 11 months; no particular abnormalities were observed at this stage apart from an unusual variation in fibre size. A distinctly below average muscle fibre diameter, increased endomysial connective tissue, and features typical for CNM were found in a biopsy taken 9 yr later. Immunohistochemical studies using antibodies to desmin, vimentin, laminin and type IV collagen revealed altered staining patterns compared with normal fibres. The abnormalities in the patterns of cytoskeletal proteins point to a defective regulation of the composition and organization of the cytoskeletal network during development, paralleled by abnormalities in the extracellular matrix.

Cell Nucleus↗
PubMed1991

MELAS syndrome. Report of two patients, and comparison with data of 24 patients derived from the literature.

We present two unrelated MELAS patients, and compare them with 24 patients derived from the literature. In most patients the stroke-like features of the MELAS syndrome occur late in the course of the disease. The diagnosis is based on characteristic clinical symptoms, presence of lactic acidemia, mitochondriopathy in muscle, and low density lesions on cerebral CT, most frequently occurring in the posterior and parieto-temporal regions. In some cases, a metabolic defect could not be demonstrated, in other cases a partial deficiency of various respiratory chain enzymes was found.

Biopsy↗
PubMed1990

[15 years of national screening for phenylketonuria in The Netherlands; 4th Report of the National Commission for Management of Phenylketonuria].

In the period 1st September 1974 to 1st January 1989 2,511,000 infants (99.3% of all livebirths) were screened for PKU. Treatment was required in 158 of the 330 referred infants. The diagnosis of these 158 patients was PKU (137), hyperphenylalaninaemia (HPA) (19) and malignant HPA (2). Three cases had a false-negative screening result. The prevalence of PKU, treated HPA and malignant HPA in the Netherlands is 1:18,000, 1:132,000 en 1:1,300,000. Height adjusted for age was in 24% of the patients with PKU of Dutch parents and weight adjusted for height in 11% under the 10th centile. Ninety per cent of the patients with PKU of 5 years and older attended primary or secondary school, compared with 95% in the general population.

Community Participation↗
PubMed1990

Deficiency of the alpha and beta subunits of pyruvate dehydrogenase in a patient with lactic acidosis and unexpected sudden death.

An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. Autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles x min-1 x mg protein-1, control range 2.8-8.7) and moderately decreased PDHC activity in fibroblasts (0.27 nmoles x min-1 x mg protein-1, control range 0.37-2.32). The activity of the first component E1 (pyruvate dehydrogenase) in muscle tissue was 10 times lower than that of controls (0.008 nmoles x min-1 x mg protein-1, control range 0.10-0.25). The activities of dihydrolipoyl dehydrogenase (E3) and various other mitochondrial enzymes were normal. Immunochemical analysis in skeletal muscle tissue and fibroblasts demonstrated a decrease in the amount of the alpha and beta subunits of E1. The features of this patient are compared with those of other patients reported in the literature with immunochemically confirmed combined E1 alpha and beta deficiency.

Acidosis, Lactic↗
PubMed1990

Isolated and combined deficiencies of NADH dehydrogenase (complex I) in muscle tissue of children with mitochondrial myopathies.

We describe eight children with complex I deficiency, four of them with an isolated, the other four with an additional deficiency of complex IV. Clinical, chemical and morphological findings were compared from patients with isolated and combined deficiency. In both groups, the age of onset of symptoms was between the 1st day and the 4th month of life. Clinical and biochemical heterogeneity were observed. We found no correlation between residual activity of complex I in muscle, blood lactate level, and severity of clinical symptoms. Newborns presenting with severe lactic acidosis and children with later onset myopathy were seen in both groups. The group with combined complex I deficiency showed a more severe clinical course. By light microscopy ragged red fibres were only found in two patients with combined deficiency. However, by electron microscopy structural alterations of the mitochondria were observed in six out of seven muscle specimens.

Biopsy↗
PubMed1990

GM2-gangliosidosis. Clinical and biochemical aspects of four cases.

We discuss four cases of GM2-gangliosidosis. In one of them the biochemical diagnostic confirmation was difficult. This case revealed striking discrepancies between the results of different methods of enzyme assay. The hexosaminidase A determination based on pH inactivation is not always reliable; assay with natural substrate may be necessary. However, the results with the newly developed substrate 4-MU-GlcNac-6-SO4 are promising and it seems to be a good alternative to the traditional (pH or heat) inactivation procedures. The deficiency can be shown in leukocytes, plasma and fibroblasts with the 6-sulfated substrate. The carrier state seems better reflected in plasma hexosaminidase A than in leukocyte hexaminidase A levels.

Adult↗
PubMed1989

Fatal neonatal cardiomyopathy associated with cataract and mitochondrial myopathy.

Three patients suffering from the neonatal form of a syndrome characterized by congenital cataract, hypertrophic cardiomyopathy, and mitochondrial myopathy are described. The patients died at 7, 10 and 18 days, respectively from cardiorespiratory failure. Mitochondrial abnormalities were observed in the heart and skeletal muscle. Despite the presence of a severe lactic acidaemia pointing to a disturbed pyruvate oxidation rate in vivo, a normal pyruvate oxidation rate was demonstrated in skeletal muscle homogenates. The activities of several enzymes of the mitochondrial respiratory chain appeared to be normal, indicating an intact respiratory chain. A myoglobinopenia could be excluded. The activities of some mitochondrial enzymes and the concentration of myoglobin increase with age.

Autopsy↗
PubMed1989

Congenital muscular dystrophy.

We report the cases of 18 patients with congenital muscular dystrophy, six of whom also have involvement of the central nervous system, corresponding to the Fukuyama type of congenital muscular dystrophy. In four patients, both the central nervous system and the eyes are involved, and the diagnosis of "muscle, eye and brain disease" was made. A comparative study of these patients with those whose cases were recently reported indicates that there is a wide variability of clinical and laboratory expression of the dystrophy, but a constant feature in all patients is a progression of motor disability. The association of congenital muscular dystrophy with brain abnormalities indicates a poor clinical prognosis. At present it remains an open question whether the three variants of the disease are separate diseases or only different expressions of the same syndrome, but our study tends to support the latter hypothesis.

Brain↗
PubMed1989

[Sphingomyelinase activity in a patient with Niemann-Pick disease].

In a few months old baby a visceromegaly was found, without other clinical abnormalities. Using an artificial substrate a deficiency of sphingomyelinase could not be demonstrated. Histopathological examination of biopsied liver revealed a lipid storage disease. Using the natural substrate the deficiency of sphingomyelinase could be demonstrated in leucocytes and in cultured fibroblasts.

Humans↗
PubMed1989

[Mitochondrial defects].

Mitochondrial myopathies are characterized by structural and functional abnormalities of the mitochondria. The diseases are best classified according to the underlying biochemical defect. In this article the variability of clinical expression and mitochondrial abnormalities is illustrated. An exact diagnosis is a prerequisite for a rational therapy and genetic counseling. In exceptional cases antenatal diagnosis should be possible.

Adenosine Triphosphate↗
PubMed1988

Estimation of pyruvate dehydrogenase (E1) activity in human skeletal muscle; three cases with E1 deficiency.

Pyruvate dehydrogenase (E1) catalyzes the rate-limiting step of the pyruvate dehydrogenase complex. Since E1 activity of human muscle tissue is low, a sensitive method is needed for diagnostic purposes. Measurement of 14CO2 production from [1-14C]pyruvate provides a specific and sensitive assay for measuring E1 activity. We use as artificial electron acceptor dichlorophenolindophenol (DCPIP) instead of the often applied ferricyanide. The method can be applied to small muscle samples obtained by needle or open biopsy. We prefer to use total homogenate because E1 activities in homogenate are higher than in the corresponding 600-g supernatant of skeletal muscle tissue. Control values in homogenate are higher or of the same order as those reported by others.

Adolescent↗
PubMed1988

Disorders of the mitochondrial respiratory chain: clinical manifestations and diagnostic approach.

The clinical identification of patients with defects in the mitochondrial respiratory chain is almost impossible. We describe screening tests that should be performed in order to select those patients in whom a skeletal muscle biopsy should be carried out for more specific biochemical assays. The importance of performing in vivo function tests is stressed. The biochemical diagnosis in disorders of the respiratory chain is presented and the application of immunological methods discussed.

Biopsy↗