Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benign enlargement of the subarachnoid spaces was diagnosed in 41 infants on the basis of ultrasound and/or CT scan findings. 10 MHz transfontanellar ultrasonography is without doubt the most reliable investigation in this condition (skull-to-cortex distance greater than 5 mm). Patients with extracerebral collections due to a clearly identifiable pathologic process (e.g., prematurity, IUGR, neonatal distress, malnutrition) were excluded from the study. Macrocrania developed rapidly in 72% of patients, either as the single manifestation (30%) or with delayed motor development and hypotonia (30%). Other clinical patterns included evidence of intracranial hypertension (15%) and hypotonia without macrocrania (20%). The two main findings of this study were the high rate of familial forms and the severity of early hemorrhagic complications, i.e., spontaneous subdural hematoma (5/41 cases), with permanent neurologic impairment in some instances (2/5 cases). These complications call into question the benignity of this syndrome whose long-term outcome, particularly in terms of cognitive function, is as yet unknown.
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PMID:[Idiopathic pericerebral swelling (external hydrocephalus) of infants]. 146 2

Protein-energy malnutrition (PEM), a natural ramification of poverty, continues to be a perennial source of concern to a large segment of the world population. The developing nervous system of a child is specially vulnerable to deprivations in nurture. Peripheral nerve and muscle derangements are clinically evident by weakness, hypotonia and hyporeflexia in accordance with severity and duration of PEM. Motor and sensory nerve conduction studies exhibit significant abnormalities and often furnish useful and ominous correlation with grades of PEM. The human sural nerve histology in cases of severe PEM is characterized by persistence of small myelinated fibres, striking failure of internodal elongation and significant segmental demyelination. Young rhesus monkeys are ideal experimental PEM models and they show myopathic EMG changes amenable to rehabilitation. Muscle pathology comprises obliteration of cross-striations, streaming of Z bands, increased interfibrillary spaces, mitochondriomegaly and small-for-age fibres. Radioisotope assays reveal anomalous incorporation into various nerve and muscle constituents. Central nervous system, specially the neuropsychological functions are affected in a lasting manner. Learning deficits, behavioural problems and manual indexterity are most obtrusive features.
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PMID:Protein energy malnutrition and the nervous system. 150 74

Malnutrition is a worldwide problem of enormous magnitude. The growth of the central nervous system in human beings is retarded in case of malnutrition in the very early part of life. Likewise, the peripheral nerves in infants and children and young growing animals appear susceptible to nutritional deprivation including protein as well as protein-calorie deficiency. Motor weakness, hypotonia, and hyporeflexia in infants and children are the essential clinical neurological signs in protein-calorie malnutrition (PCM). Motor and sensory nerve conduction are significantly impaired in children with PCM as well as in animals subjected to protein or protein-calorie deficiency. Histological studies have revealed reduced diameter of myelinated nerve fibers, retardation of myelination, segmental demyelination and remyelination, axonal degeneration, and shortened longitudinal growth of internodes. Diffusion barrier by perineurium may be broken. There is reduction in myelin lipids and impaired synthesis of myelin as shown by the biochemical and radioisotope incorporation studies. Presence of cholesterol esters in the biochemical synthesis of nerves suggests degeneration changes. Experimental studies have revealed that most effects of PCM on peripheral nerves can be reversed by nutritional rehabilitation, although complete recovery in the sensory nerve action potential, fiber size of dorsal nerve roots, and myelin-specific lipids does not occur. Skeletal muscle also shows many changes including muscle fiber atrophy, reduction in duration and amplitude of motor unit potentials, and/or fibrillation on electromyography (EMG) and biochemical estimation of muscle enzymes. These changes may be the reflection of a direct effect of PCM on muscles or secondary to the abnormal structural or biochemical changes in the peripheral nerves. PCM affects the central nervous system, especially the neuropsychological functions, in a lasting manner. Learning deficits and impairment of manual dexterity are the most obtrusive features. Neurotransmitter abnormalities and maturation lag in electroencephalogram have been demonstrated in experimental animals. Spinal cord dysfunction sometimes manifests overtly as clinical myelopathy. Degenerative changes in the cerebellum have been noted.
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PMID:Neurological consequences of protein and protein-calorie undernutrition. 193 90

Forty-three children (aged 7 to 62 months) with protein calorie malnutrition (PCM) were studied; 13 had mild to moderate PCM and 30 severe PCM. A reduction of motor nerve conduction velocity and abnormalities of sensory conduction were present in both groups. The abnormality of motor nerve conduction was directly related to the severity of PCM and the presence of hypotonia and/or hyporeflexia. Sural nerve biopsies from both groups were studied for myelinated fibre density, fibre size spectrum, relationship of internodal length with diameter and qualitative light microscopic changes. The biopsies from children with mild to moderate PCM were characterized by a normal developmental change in myelinated fibres with an increasing proportion of medium and large size fibres, a transition from a unimodal to a bimodal distribution and an appropriate relationship of internodal length to fibre diameter. Evidence of mild segmental demyelination was observed in only one patient of this group. In contrast, in the biopsies from children with severe PCM, the normal developmental pattern for myelinated fibre size distribution was impaired with a persistence of small myelinated fibres, and there was a failure of internodal segments on large fibres to elongate with increase in age and significant segmental demyelination in about 50 per cent of cases. Retarded myelination and segmental demyelination probably form the morphological basis for impaired peripheral nerve function in PCM. Short internodes on large diameter fibres may also contribute to this effect.
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PMID:Effect of protein calorie malnutrition on peripheral nerves. A clinical, electrophysiological and histopathological study. 308 65

Patients with the cerebrohepatorenal syndrome of Zellweger lack peroxisomes and certain peroxisomal enzymes such as dihydroxyacetone phosphate acyltransferase in their tissues. Deficiency of this enzyme, which is necessary for glycerol ether lipid synthesis, provides a biochemical method for recognizing patients with subtle manifestations of Zellweger syndrome and suggests the utility of exogenous ether lipid precursors as a therapeutic strategy for these children. We describe the results of glycerol ether lipid supplementation to two children, one with classic Zellweger syndrome and 9% of control fibroblast dihydroxyacetone phosphate acyltransferase activity, and one with mild facial manifestations, wide sutures, hypotonia, developmental delay, hepatomegaly, peripheral retinal pigmentation, and 50% of control fibroblast dihydroxyacetone phosphate acyltransferase activity. An increase in erythrocyte plasmalogen levels following therapy was clearly demonstrated in the milder patient, and neither patient showed evidence of toxicity. Evaluation of therapy by comparison to the usual clinical course of Zellweger syndrome was not helpful because of the variability and incomplete documentation of 90 previously reported cases. The literature survey did provide criteria for classic Zellweger syndrome, which include hypotonia with or without deformation of limbs, large fontanels and split sutures, prominent forehead, flattened facial profile with hypoplastic supraorbital ridges, anteverted nares, highly arched palate, cryptorchidism or labial hypoplasia, hepatomegaly or elevated liver enzymes, peripheral pigmentation of the retina, renal cortical cysts, and characteristic neuropathology involving decreased myelinization, abnormal neuronal migration, and sudanophilic macrophages. Less severe patients, as exemplified by our case 2 and others from the literature, will not have all the classic features and can be recognized only by a growing panel of biochemical indicators. Our patient studies illustrate the complexity of designing comprehensive therapy for Zellweger-like conditions, suggest other diseases that may involve peroxisomal alterations, and emphasize the need for multicenter, collaborative studies to evaluate biochemical heterogeneity and therapy of peroxisomal disorders.
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PMID:Zellweger syndrome: diagnostic assays, syndrome delineation, and potential therapy. 370 14

Phosphorus depletion in malnutrition has not generally received attention. Serum phosphorus was measured in healthy infants (1.8 mmol/L), in well-nourished infants with acute dehydrating gastroenteritis, and in infants suffering from malnutrition. Serum phosphorus levels were found to be low in well-nourished infants with acute dehydrating gastroenteritis (1.32 mmol/L) an exceptionally low in infants with kwashiorkor (1.10 mmol/L) especially when the latter condition was accompanied by severe diarrhoea (0.66 mmol/L). Hypophosphatemia, as well as hypokalemia, was associated with marked hypotonia. Low levels of serum phosphorus occurred in nine of the 10 malnourished children who died.
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PMID:Serum phosphorus in protein energy malnutrition. 682 Nov 15

Glutaric acidemia type II is associated with neonatal hypoketotic hypoglycemia, metabolic acidosis, profound hypotonia, progressive cardiomyopathy, and early death. Deficiency of either electron transfer flavoprotein or electron transport flavoprotein:ubiquinone oxidoreductase leads to intramitochondrial accumulation of metabolites of compounds oxidized by enzymes that transfer electrons to flavoprotein. No detailed results of antemortem neuroimaging or magnetic resonance spectroscopy have been described previously. We investigated a patient with typical neonatal onset glutaric acidemia type II without obvious dysmorphogenesis or renal malformations. Cranial tomographic scan revealed hypoplastic temporal lobes and marked widening of the sylvian fissures ("bat-wing" appearance). Cranial magnetic resonance imaging documented underdeveloped frontal and temporal lobes with delayed myelination and hypoplasia of the corpus callosum. 31P-Magnetic resonance spectroscopy of muscle was grossly abnormal with a very low energy state consistent with mitochondrial dysfunction. 1H-Magnetic resonance spectroscopy of brain revealed elevated intracerebral lactate concentration and abnormally high choline/creatine ratio suggestive of dysmyelination. These findings constitute the first in vivo evidence of a developmental encephalomyopathy in glutaric acidemia type II.
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PMID:Glutaric acidemia type II: neuroimaging and spectroscopy evidence for developmental encephalomyopathy. 754 9

Deficiency of cytochrome c oxidase activity was established in a girl born to consanguineous parents. She showed symptoms of dysmaturity, generalized hypotonia, myoclonic seizures and progressive respiratory failure, leading to death on the seventh day of life. Structural abnormalities of the central nervous system consisted of severe cerebellar hypoplasia and optic nerve atrophy. Biochemical analysis of a muscle biopsy specimen demonstrated deficiency of cytochrome c oxidase activity. Cultured fibroblasts from this patient also showed a selective decrease in the activity of cytochrome c oxidase, excluding a muscle-specific type of deficiency. Further investigations in cultured fibroblasts revealed that synthesis, assembly and stability of both the mitochondrial and the nuclear subunits of the enzyme were entirely normal. The steady-state concentration of cytochrome c oxidase in the fibroblasts of the patient was also normal, suggesting that the kinetic properties of the enzyme were altered. Analysis of the kinetic parameters of cytochrome c oxidase demonstrated an aberrant interaction between cytochrome c oxidase and its substrate, cytochrome c, most likely because of a mutation in one of the nuclear subunits of the enzyme.
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PMID:Altered kinetics of cytochrome c oxidase in a patient with severe mitochondrial encephalomyopathy. 772 43

There are two genetically determined biotin-dependent disorders. The first is holocarboxylase synthetase (HCS) deficiency and the second biotinidase deficiency. HCS catalyzes the reaction in which active holocarboxylases are synthesized from inactive apocarboxylases. Biotin is required for this synthesis. Biotinidase facilitates the release and recycling of free biotin. Deficiency of either HCS or biotinidase is characterized by certain neurological, cutaneous and biochemical abnormalities. In this paper, six patients with biotinidase and two patients with HCS deficiency are described. Among the most common neurological findings were hypotonia (6/8), seizures (2/6) and optic atrophy (2/8). Dermatitis and conjunctivitis were present in three and four patients, respectively. All patients had low blood pH bicarbonate levels. Serum lactate was increased in all and pyruvate in six cases. Two patients with biotinidase deficiency presented earlier than the mean age of onset previously reported in the literature. Detection of eight cases during the past few years at a single metabolic unit indicates that biotinidase deficiency is not rare in Turkey, where the frequency of some other metabolic disorders has also been reported to be high. We suggest that biotin-dependent disorders should be considered in all infants with neurological symptoms, particularly those with jerks, even if other signs such as alopecia, seborrheic dermatitis and acidosis are not evident, regardless of the age of presentation.
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PMID:Inborn errors of biotin metabolism. Clinical and laboratory features of eight cases. 782 32

Progressive encephalopathy, developmental delay, microcephaly, electroencephalogram (EEG) and computed tomographic (CT) scan abnormalities have been reported in 80% of children with chronic renal failure (CRF) in infancy. Malnutrition, aluminium intoxication and psychosocial deprivation are proposed as causes. In 15 children with CRF from infancy we evaluated the effect of no aluminium salts and early vigorous nutritional and psychosocial support, in addition to the standard therapy, on neurological development. Six patients underwent dialysis (2 at birth) and 3 received transplants. None of our patients were given aluminium therapy. The nutritional status of the patients in the first 2 years of life was assessed with the waterlow classification. At the end of the follow-up period (mean 50 months range 14-148 months), patients underwent neurodevelopmental assessment, head CT scan, EEG, nerve conduction velocity (NCV) and auditory brain stem evoked response (ABER). None of our patients developed progressive encephalopathy or recurrent seizures. All have a normal neurological examination apart from hypotonia. Microcephaly was present in 5 patients. There was a good correlation between malnutrition in the first 2 years of life and microcephaly. Developmental delay was present in 3 patients; all 3 were microcephalic. There was evidence of brain atrophy on CT scan in only 3 patients. EEG was abnormal in 6 patients, but only severe in 1 patient. Only 1 patient had diminished NCV; all patients had a normal ABER. We conclude that a policy of no oral aluminium therapy and early nutritional support leads to better neurological outcome in children with CRF from infancy.
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PMID:Improved neurological outcome in children with chronic renal disease from infancy. 801


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