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R C Sengers

Publications and source records attributed to R C Sengers.

At least 37 records · Page 2Linked to original sources
PubMed1997

Favourable clinical course in an infant with severe deficiency of complex III of the respiratory chain combined with less severe deficiencies of complexes I, II and IV.

UNLABELLED: An infant with severe deficiency of complex III combined with less severe deficiencies of complexes I, II and IV of the mitochondrial respiratory chain in skeletal muscle tissue presented with intra-uterine growth retardation, generalized hypotonia and delayed motor development. In the following 3.5 years muscle tone and motor development gradually normalized whereas the lactic acidosis and enzyme activities did not improve. CONCLUSION: This report documents a favourable clinical course in a child with combined respiratory chain deficiency despite persistent biochemical abnormalities.

Child, Preschool↗
PubMed1997

Clinical heterogeneity in respiratory chain complex III deficiency in childhood.

Six children are presented with an isolated complex III deficiency in muscle tissue. More specifically, oxidation rates and ATP+CrP production rates from both pyruvate and succinate as substrates and/or the activity of decylubiquinol:cytochrome c oxidoreductase were all markedly reduced. Complex III deficiency was also present in liver of two patients tested, but could not be demonstrated in cultured fibroblasts of four patients tested. Mitochondrial DNA, extracted from muscle, was analyzed; no deletions or common point mutations were found. Four patients presented with a multi-organ disorder. Among these patients three presented at neonatal age with neurological signs and lactate elevation in blood and CSF, of whom two had severe neonatal Fanconi syndrome. One child, aged seven years, had encephalomyopathy, ophthalmoplegia, retinopathy and Wolff-Parkinson-White syndrome. The remaining two patients exhibited myopathy only, within the first year of life. Thus, like in other respiratory chain disorders, patients with complex III deficiency may present at any age and show variable symptoms and outcome, ranging from neonatal death to failure to thrive only. Apparently there are no clinical findings which are specific for complex III deficiency.

Abnormalities, Multiple↗
PubMed1997

Does impaired growth of PKU patients correlate with the strictness of dietary treatment? National Dutch PKU Steering Committee.

To assess whether growth retardation in patients with phenylketonuria (PKU) is related to the strictness of their dietary treatment, the relationship between Z scores for height up to 3 y of age and different indices of dietary control in 103 early treated Dutch PKU patients was studied. As indices of dietary control, the mean phenylalanine (Phe) concentration, the frequency of plasma Phe concentrations < 200 and < 120 micromol/l, and the standard deviation of the individual plasma Phe concentrations were studied. These measures of the dietary control were divided into quartiles. The mean Z score of the studied patients showed a decrease of 0.18/y (SD 0.36). No statistically significant difference between any of the quartiles of the studied indices with growth retardation was found. None of the used indices of dietary control based on plasma Phe concentrations showed a relationship between different degrees of the strictness of dietary treatment with growth retardation in Dutch PKU patients.

Body Height↗
PubMed1997

Multicore myopathy with restrictive cardiomyopathy.

A 10-y-old girl is presented who suffered mild muscular weakness and exercise intolerance from the age of 1 y onwards, with progression appearing from the age of about 8 y. Multicore myopathy and restrictive cardiomyopathy were diagnosed. Literature concerning the coexistence of multicore myopathy and cardiomyopathy is reviewed.

Cardiomyopathy, Restrictive↗
PubMed1997

Defects in the mitochondrial energy metabolism outside the respiratory chain and the pyruvate dehydrogenase complex.

Disturbances in substrate oxidations in muscle mitochondria from patients with a suspicion of a mitochondrial myopathy may arise from a deficiency of one or more of the complexes of the respiratory chain or of the pyruvate dehydrogenase complex. However, we found no clear-cut defect in a substantial part of such patients. In this report we discuss some of the other possibilities which could account for the disturbed substrate oxidation rates. Special attention will be paid to defects which are localized outside the respiratory chain, such as defects in post-respiratory chain enzymes, defects in transport mechanisms of the mitochondrial inner or outer membrane, deficiency of cofactors and deficiency of heat-shock protein.

Electron Transport↗
PubMed1996

Myopathology in patients with a Noonan phenotype.

Two patients with a Noonan phenotype and progressive hypertrophic obstructive cardiomyopathy are described, in whom abnormal histopathological changes in striated musculature were detected. In both patients an increased density of muscle spindles was found at biopsy. The significance of an increased density of muscle spindles in patients with Noonan phenotype can only be speculated. The question is raised of whether these changes are a distinct feature within the spectrum of patients with Noonan phenotype.

Cardiomyopathy, Hypertrophic↗
PubMed1995

Multiple deficiencies of mitochondrial DNA- and nuclear-encoded subunits of respiratory NADH dehydrogenase detected with peptide- and subunit-specific antibodies in mitochondrial myopathies.

Antibodies have been raised against synthetic peptides corresponding to several computer-predicted epitopes of three mtDNA-encoded subunits, ND4, ND5 and ND6, of the human respiratory chain NADH dehydrogenase (Complex I). Antibodies were characterized by a sensitive immunoblotting assay using proteins from human skeletal muscle mitochondria and by immunoprecipitation of radio-labeled HeLa cell mitochondrial translation products. Only antibodies against two of six selected peptides of the ND4 subunit, i.e., the C-terminal peptide and an internal peptide close to the C-terminus, reacted in both assays with the subunit. Antibodies raised against an internal peptide close to the N-terminus of the ND5 subunit and antibodies raised against an internal epitope of the ND6 subunit also reacted in both the immunoblotting and immunoprecipitation assays. The antibodies described above and other Complex I subunit- or holoenzyme-specific antibodies were used to investigate the subunit deficiencies of the respiratory NADH dehydrogenase in the skeletal muscle of patients affected by mitochondrial myopathies associated with Complex I defects. The reduction in enzyme activity correlated in an immunoblot assay with a decrease of four mtDNA-encoded subunits of the enzyme, as well as with a decrease of other subunits of Complex I encoded in the nDNA. The present work provides the first evidence of a decrease in NADH dehydrogenase subunits encoded in the mitochondrial genome in myopathy patients.

Adolescent↗
PubMed1995

Neonatal De Toni-Debré-Fanconi syndrome due to a defect in complex III of the respiratory chain.

A patient with neonatal expression of severe De Toni-Debré-Fanconi syndrome is presented. Because of early signs of renal tubulopathy together with a large urinary excretion of lactate, 3-hydroxybutyrate and citric acid cycle intermediates, a mitochondrial disorder was suspected and muscle and liver biopsies were performed. Biochemical investigations in both tissues revealed a defect in the respiratory chain at the level of complex III. In this patient renal dysfunction was the primary symptom, and hyperlactataemia, an important clue for a mitochondrial disorder, was lacking. CONCLUSION. Complex III deficiency should be included in the differential diagnosis of neonatal De Toni-Debré-Fanconi syndrome.

Electron Transport↗
PubMed1995

White matter abnormalities in congenital muscular dystrophy.

Central nervous system (CNS) characteristics were examined in seventeen patients with autosomal recessive classic or "pure" congenital muscular dystrophy (CMD). In three patients, neuroradiological examination (CT/MRI) indicated hypodense white matter areas. Two out of these three patients had epilepsy (seizures and epileptic discharges on their EEG). Only two of the remaining patients had epileptic EEG discharges, but without clinical seizures. By comparing our results to data in the literature, we could conclude that the classic or "pure" form of CMD can be subdivided into two subtypes, i.e. those with and those without white matter hypodensities. A mild form of epilepsy or an epileptic predisposition on EEG can be part of the subtype with white matter hypodensities.

Adolescent↗
PubMed1995

Immunophenotyping of congenital myopathies: disorganization of sarcomeric, cytoskeletal and extracellular matrix proteins.

We have studied the expression and distribution patterns of the intermediate filament proteins desmin and vimentin, the sarcomere components titin, nebulin and myosin, the basement membrane constituents collagen type IV and laminin, and the reticular layer component collagen type VI in skeletal muscle of patients with "classic" congenital myopathies (CM), using indirect immunofluorescence assays. In all biopsy specimens obtained from patients with central core disease (CCD), nemaline myopathy (NM), X-linked myotubular myopathy (XLMTM) and centronuclear myopathy (CNM), disease-specific desmin disturbances were observed. Vimentin was present in immature fibres in severe neonatal NM, and as sarcoplasmic aggregates in one case of CNM, while the amounts of vimentin and embryonic myosin, observed in XLMTM, decreased with age of the patients. Abnormal expression of myosin isoforms was found in several CM biopsies, although the organization of myosin and other sarcomere components was rarely disturbed. Basement membrane and reticular layer proteins were often prominently increased in severe cases of CM. We conclude that (i) desmin is a marker for individual types of CM and might be used for diagnostic purposes; (ii) the expression patterns of the differentiation markers desmin, vimentin and embryonic myosin in XLMTM, point either to a postnatal muscle fibre maturation or to a variable time-point of maturational arrest in individual patients; (iii) the correlation between the distribution patterns of extracellular matrix proteins and clinical presentation points to a role of these proteins in pathophysiology of CM.

Adolescent↗
PubMed1995

Abnormal expression of intermediate filament proteins in X-linked myotubular myopathy is not reproduced in vitro.

Expression patterns of the intermediate filament proteins (IFPs) desmin and vimentin, in biopsy material taken from a 1 day old boy with fatal neonatal X-linked myotubular myopathy (XLMTM) were compared with the expression of these proteins in cultured myotubes, from the same patient. Immunohistochemical studies revealed the persistence of high levels of desmin in virtually all, and vimentin in most, of the myofibres within the patient's biopsy. Analysis of intermediate filament expression in differentiating, cultured muscle cells did not reveal overt differences between XLMTM cultures and cultures of control muscle. Titin distribution patterns indicated a normal process of myofibrillogenesis in XLMTM myotubes. We conclude that the failure to properly regulate IFP-expression is not intrinsic to XLMTM muscle fibres. The possibility that this failure is due to a defective external, possibly neural factor, is discussed.

Cells, Cultured↗
PubMed1994

The phenylalanine response curve in relation to growth and mental development in the first year of life.

Thirty-three children with classical phenylketonuria were treated from 9 to 21 days of age onward. The standard for phenylalanine concentration was 0.2-0.5 mmol/l. During the first years of life phenylalanine concentrations were measured once every two to six weeks. For each child these values were graphically plotted in a so-called phenylalanine response curve. Growth and mental development indices were assessed at about one and two years of age. Measurements for weight, height and head circumference were normal at one month of age, showed a significant decline at the age of one year but were restored for normal values at the age of two. No associations were found with phenylalanine parameters. Mental development indices at one and two years were not different from normal. Significant negative correlations were found between mental development indices at one year and phenylalanine values above 0.5 mmol/l. Changes in mental development indices between the first and second years of life are significantly related to the phenylalanine levels during the second year of life.

Child, Preschool↗
PubMed1994

Predictors of mean phenylalanine levels during the first five years of life in patients with phenylketonuria who were treated early. Dutch National PKU Steering Committee.

We studied the relationship between plasma phenylalanine level at first diagnostic visit, country of origin of the mother, birth cohort, child clinic, sex, and social class on the one hand and mean plasma phenylalanine levels in the first five years of life on the other hand in patients with phenylketonuria (PKU) who were treated early. The study population consisted of 131 early treated patients with PKU born during the period from September 1st, 1974 to December 31st, 1988 in The Netherlands. Plasma phenylalanine levels from first diagnostic visit (usually before the age of three weeks) up until the fifth birthday were registered. For each patient the mean phenylalanine level during that period was calculated. Our results suggest that 1) it is more difficult to maintain low phenylalanine levels in patients with a more severe form of PKU, 2) in recent years paediatricians have treated their patients with a stricter diet, 3) there are differences in perception between paediatricians of different clinics as to what levels are acceptable, and 4) treatment of patients from non-Dutch mothers is more difficult than treatment of patients with Dutch mothers.

Age Factors↗
PubMed1994

Impaired prenatal and postnatal growth in Dutch patients with phenylketonuria. The National PKU Steering Committee.

OBJECTIVE: To assess whether physical growth is affected in early treated Dutch patients with phenylketonuria (PKU). METHODS: The birth weights of all 137 early detected patients with PKU born in the period from 1974 to 1988 in the Netherlands were compared with reference values. Height, head circumference, and weight were measured at the age at which treatment started (commonly about 2-3 weeks), at 6 months of age, and yearly from the child's first birthday up to the age of 10 years. These measurements were compared with reference values. RESULTS: The adjusted birth weight in patients with PKU was 141 g (95% confidence interval (CI) 66 to 216 g) less than Dutch reference values by Kloosterman and 103 g (95% CI 9 to 196 g) less compared with the birth weight of another reference group. At the age at which treatment started, z scores of patients for height by age were -0.23 (95% CI -0.44 to -0.02) and z scores for head circumference by the age were -0.25 (95% CI -0.44 to -0.06). From the age at which treatment started up to the age of 3 years z scores for height by age further decreased to -0.74 (95% confidence interval -0.93 to -0.56), after which no additional decrease occurred. In contrast, z scores for head circumference increased from -0.25 at the first visit to 0.08 (95% CI -0.14 to 0.30) at the age of 1 year, after which they remained close to zero. Weight by height was close to the expected centiles for all ages. CONCLUSION: Patients with PKU are growth retarded at birth and have smaller head circumferences than the normal population. In Dutch patients further growth retardation occurs in the first three years of life.

Anthropometry↗
PubMed1993

X-linked ataxia, weakness, deafness, and loss of vision in early childhood with a fatal course.

An X-linked recessive disease with, in almost all patients, a fatal course in early childhood, occurring in a five-generation family is described. The 12 affected boys had early-onset floppiness, ataxia, liability to infections especially of the upper respiratory tract, deafness, and later, a flaccid tetraplegia and areflexia. Eleven boys died before the age of 5 years. One boy is still alive at the age of 12 years, but in addition to the above-mentioned signs, he must be ventilated at night and is nearly blind due to optic atrophy. In the only patient whose central nervous system could be examined at the time of autopsy, an almost complete absence of myelin in the posterior columns of the spinal cord was found. This may be the main pathological substrate for the neurological findings. No biochemical or immunological defects were detected. The family also counted 16 healthy male siblings and 13 definite of 28 possible female carriers. Some carriers developed a hearing impairment in early adulthood. As far as is known now, this disease has not been described before.

Ataxia↗
PubMed1993

Congenital muscular dystrophy. A study on the variability of morphological changes and dystrophin distribution in muscle biopsies.

Histomorphological and histochemical variability was studied in muscle specimens from 30 patients with congenital muscular dystrophy (CMD). We found involvement of the central nervous system in 8 patients (Fukuyama CMD, F-CMD), involvement of the brain and the eyes in 5 patients (muscle, eye and brain disease, MEB-D) and hypodense white matter on the CT scans of 2 patients with (sub)normal intelligence (occidental-type cerebromuscular dystrophy, O-CMD). No morphological hallmarks were found to differentiate these subgroups. Only fat cell infiltration was found to be increased with increasing age in 'pure' CMD (pure-CMD). The morphological data did not appear to be correlated with the clinical severity or type of dystrophy (pure-CMD, F-CMD, MEB-D and O-CMD). Immunohistochemistry with dystrophin, vimentin and desmin antibodies in 14 patients (6 pure-CMD, 5 F-CMD, 2 MEB-D and 1 O-CMD) showed a normal expression pattern.

Child↗