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Biomedical subjects

W F Arts

Publications and source records attributed to W F Arts.

At least 55 records · Page 3Linked to original sources
PubMed1987

Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells.

Mitochondria are very vulnerable to genetic and environmental damage. If a patient is suspected of having a mitochondrial disease, elevated blood lactate, lowered blood free carnitine, abnormal urinary organic acids and carnitine esters and tissue histopathology may help with the diagnosis. For biochemical assessment of the defect, muscle is the tissue of choice even when involvement of other organs like heart or brain is more prominent. We have studied isolated muscle mitochondria and homogenates from muscle biopsies in 250 patients, and have detected in more than one third mitochondrial defects in oxidative phosphorylation, dehydrogenases, non-redox enzymes catalyzing synthesis of fuel molecules and in the carnitine system. Several patients showed more than one defect. We have selected eight patients to illustrate how a relatively simple series of investigations in both isolated mitochondria and homogenate can be used for the identification of defects in oxidative phosphorylation in a small amount of muscle (200 mg or more). Identification of the defect(s) is important since it may provide the basis for rational treatment. A minority of the patients recovered partly or completely, which is unique in treatment of inborn errors of subcellular organelles. An important aspect of mitochondrial dysfunction is the tissue specificity. The defect may be systemic but is often clinically expressed in only one or a few tissues. Rarely, tissue-specific defects can be understood on the basis of tissue-specificity of mitochondrial (iso-)enzymes. Mitochondrial deficiencies of all biotin enzymes and most CoA-linked enzymes are expressed in fibroblasts; most respiratory chain defects are not. When mitochondrial ATP synthesis has been compromised by a mitochondrial defect, secondary lesions may be generated by changes in mitochondrial protein synthesis, activated proteases and phospholipases, increased matrix CoA and resulting carnitine deficiency, decrease in Krebs cycle intermediates and increased free radical formation and lipid peroxidation.

Adolescent↗
PubMed1987

Cytochrome c oxidase deficiency in subacute necrotizing encephalomyelopathy.

Two new patients with Leigh's syndrome (subacute necrotizing encephalomyelopathy) due to deficiency of cytochrome c oxidase are presented and their data are compared with those of the four Leigh's syndrome patients previously reported with this deficiency. It is not possible to distinguish between the various biochemical aetiologies of Leigh's syndrome on clinical grounds. Investigation of pyruvate metabolism and of the respiratory chain will reveal the enzymatic defect in some of the patients. It has now been firmly established that a relationship exists between Leigh's syndrome and deficiency of cytochrome c oxidase. There are, however, other syndromes which are also associated with a deficiency of this enzyme. In Leigh's syndrome, the enzyme deficiency has been reported in many organ systems and in cultured fibroblasts. In the liver, however, decreased, intermediate or normal values of cytochrome c oxidase activity have been found. Selective or more widespread involvement of organ systems, due to mutations of either the nuclear or the mitochondrial DNA encoding for different subunits of the enzyme molecule (some of which may be organ- or tissue-specific), could explain the clinical and biochemical heterogeneity of syndromes associated with a cytochrome c oxidase deficiency.

Brain↗
PubMed1987

Cerebral thromboembolism due to antithrombin III deficiency in two children.

Despite numerous well-described causes of stroke in infancy and childhood, a significant proportion remains unexplained. Venous thromboembolism is a common complication in adult patients undergoing surgery, and after severe trauma, but not in otherwise healthy children less than 10 years old. However, it may also occur spontaneously without recognizable cause. It has been known for a long time that some patients are particularly prone to venous thrombosis and in recent years great efforts have been made to identify the risk factors. The attention of haematologists has been focused on the possibility that certain abnormalities of coagulation may be associated with a tendency to thrombosis, but only in a few instances a clear causal relationship has been established. One such example is a deficiency of antithrombine III, but such a deficiency has hitherto been recognized as a cause for thrombosis in children only in very particular circumstances. We present two young children with stroke of which one was purely ischemic and the other ischemic with secondary hemorrhage. Both our patients showed an AT III deficiency. Patient one also had a cyanotic congenital heart disease with right to left shunting which made cerebral embolism originating from a thrombus in the iliac vein possible to occur. We consider her hematocrit values too low to be a predisposing factor for this thrombosis. AT III deficiency may be caused by several different mechanisms. Either it exists as a congenital (hereditary) or as an acquired disorder. In patient two the family history was positive for hereditary AT III deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III Deficiency↗
PubMed1987

Acquired dysarthria in childhood: an analysis of dysarthric features in relation to neurologic deficits.

We analyzed the dysarthria of four children with bilateral supranuclear facial palsy and four with bilateral peripheral facial palsy. The children with peripheral lesions had only moderate dysarthria, characterized mainly by weakened vowels and consonants and by hypernasality. In contrast, children with supranuclear lesions were anarthric at first, followed by severe dysarthria with reduced stress and many pauses. Although there was a relation between severity of dysarthria and neurologic disorders, anarthria can be seen in children with bilateral supranuclear lesions and only slight neurologic disability. Damage to cortical or brainstem control mechanisms may be responsible.

Adolescent↗
PubMed1986

Intracranial calcified deposits in neurofibromatosis.

Three patients with the central type of neurofibromatosis, who on CT showed multiple subependymal calcified deposits, are presented. The literature on intracranial non-tumourous calcifications in neurofibromatosis is briefly reviewed. On the basis of our findings and the literature, it is proposed that such intracranial calcified deposits may be part of the neurofibromatosis syndrome and are caused by calcium deposits in glial proliferations, analogous to the calcified deposits seen in tuberous sclerosis.

Adolescent↗
PubMed1985

Late-onset globoid cell leucodystrophy (Krabbe's disease). Clinical and genetic delineation of two forms and their relation to the early-infantile form.

A girl is described with a late-onset form of globoid cell leucodystrophy (GLD, Krabbe's disease). Data of this patient and seventeen reported patients with late-onset GLD and cerebroside-beta-galactosidase deficiency were compared with those of patients with classical early-infantile GLD. Three phenotypes of GLD are proposed, an early-infantile form, and two late-onset forms. Biochemical studies demonstrated residual activities of cerebroside-beta-galactocerebrosidase in the late-onset forms. The KM values were identical in the three GLD phenotypes. Autosomal recessive inheritance is likely for each of the subtypes. Complementation studies by somatic cell hybridization suggest that the mutations in early-infantile and late-onset GLD are allelic.

Cerebrosides↗
PubMed1985

Segmental neurofibromatosis.

A child with segmental neurofibromatosis is reported. The clinical, histopathological and ultrastructural characteristics of this rare condition are described. This entity is considered to be a localized form of von Recklinghausen's disease. The aetiology is not clear, but somatic mutation in early embryonic development may be important.

Follow-Up Studies↗
PubMed1984

Combined sialidase (neuraminidase) and beta-galactosidase deficiency. Clinical, morphological and enzymological observations in a patient.

A patient with combined deficiency of sialidase and beta-galactosidase is described. This now 39-year-old man, who is of Japanese origin, showed gradually progressive clinical features from the age of six years. Many of these features are commonly found in sialidosis type 2 or in GM1-gangliosidosis. Both sialidase and beta-galactosidase activities were deficient in leucocytes and cultured fibroblasts. Leucocytes of his mother showed activities of both enzymes in the lower limit of the control range. Morphologically, the pattern of storage products in a skin biopsy resembled in many respects that seen in GM1-gangliosidosis. Moreover, storage products which could be typical of sialidosis were also observed. Since the patient showed angiokeratomata, the morphological findings were compared with those specific to Fabry's disease, but no similarities were found. An enzymological diagnosis of the disease is most reliable on cultured fibroblasts, discriminating it from sialidosis type 2 and GM1-gangliosidosis. In view of recent findings, leucocytes seem to be less suitable for the establishment of the diagnosis galactosialidosis.

Adult↗
PubMed1983

Congenital nemaline myopathy: two patients with consanguineous parents, one with a progressive course.

Clinical, morphological and genetic data are presented on two unrelated children with congenital nemaline myopathy. In one of these, the weakness and hypotonia were progressive. The parents of both children were second cousins. These cases together with those already published suggest that the frequency of consanguineous marriages in parents of children with nemaline myopathy is increased. This is a further argument in favour of an autosomal recessive type of congenital nemaline myopathy in addition to the autosomal dominant variety.

Biopsy↗
PubMed1983

Hereditary neuralgic amyotrophy. Clinical, genetic, electrophysiological and histopathological studies.

Clinical, genetic, electrophysiological and histopathological studies in a four-generation family with hereditary neuralgic amyotrophy (HNA) are described. Clinically two kinds of attack could be distinguished: (1) the classical type with pain and weakness lasting for weeks to months, leaving atrophy and sometimes residual weakness; 2) attacks consisting of recurrent pain and weakness lasting for a few days and occurring about once a week for several months, also resulting in persisting atrophy and weakness. Genetically a strong association was found between HNA and hypotelorism, probably due to pleiotropism of one single gene. Close linkage with any of 29 genetic markers was not present. The electrophysiological findings indicated that a local process in the brachial plexus, possibly demyelination or a conduction block, was the primary pathophysiological mechanism. Nevertheless, the sural nerve of the index case, biopsied 5 months after the onset of an attack, showed a decreased number of myelinated nerve fibres per cross-sectional area. Apparently, other parts of the peripheral nervous system may be affected subclinically in an attack of brachial plexopathy. The central and peripheral nervous system of his mother, 30 years after her last attack of HNA, showed only nonspecific changes. Tomacula were not seen in either case. HNA and hereditary liability to pressure palsies (HLPP) are distinctly different disorders.

Adolescent↗
PubMed1983

The analysis of acquired dysarthria in childhood.

A rare case of acquired dysarthria caused by a brain-stem infarct in a six-year-old boy is reported. Applying the analysis of Darley et al. (1969, 1975), 14 'dimensions' of dysarthria were recognised. The course of this dysarthria is described, by comparing samples of spontaneous speech, repetition and singing. The dysarthria is mainly characterised by imprecise consonants, distorted vowels, hypernasality and a breathy voice.

Brain Stem↗
PubMed1978

Further investigations on benign myopathy with autosomal dominant inheritance.

Six members of a family suffered from benign myopathy over four generations. The clinical, laboratory, electromyographic, histological and genetic data were consistent with benign myopathy with autosomal dominant inheritance. Congenital torticollis was a feature in one patient. Linkage studies revealed no linkage between the locus of this myopathy and the locus of any of 17 genetic markers investigated. This family was of Polish descent, which indicates a widespread occurrence of this benign hereditary myopathy. The data presented are a strong argument in favor of a specific new disease entity.

Adipose Tissue↗