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)

Two cases of triglyceride storage in liver, kidney, heart, and skeletal muscle are described in infants who died at the age of 1 1/2 years and 4 d, respectively. In the first patient, a previously normal girl, the clinical symptoms began two months before death with encephalopathy (vomiting, unconsciousness), liver enlargement, hypoglycemia, increase in serum transaminases. These signs disappeared within the following days. Some weeks later she died during the second attack. The 4-d-old boy, the second child of healthy consanguineous parents, showed at the third day of life an impaired sucking, muscular hypotonia, respiratory arrest and bradycardia. An intensive therapy was inefficient. At autopsy gross examination showed only a moderately enlarged yellow liver and an edematous brain in the first case and pale organs in the second one but no cause of death. The microscopial examination of all tissues of both cases showed fat storage within the four organs mentioned above. The common histochemical methods for neutral lipids were positive, the Schultz-reaction for cholesterol and cholesterol esters was negative. The lipid loaden cells did not show birefringence in polarized light. A predominance and strong fat storage of the type I fibres was found in the skeletal muscle. The storage of triglyceride could be confirmed by histochromatography, a thin-layer chromatography of tissue sections. The triglyceride accumulation in liver, heart, kidney, and skeletal muscle is a characteristic feature of systemic carnitine deficiency. The clinical symptoms of the first patient are in agreement with reports of this disease also. A carnitine deficiency in a newborn was not yet described. Family studies revealed a low carnitine concentration in the mother's serum in both cases, while the serum of father and brother resp. sister showed normal carnitine levels.
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PMID:[Metabolic triglyceride storage disorders. A report of 2 cases of systemic carnitine deficiency]. 652 56

Our purpose was to perform the first systematic neurological, neurophysiological and psychological study of 18 patients with Cohen syndrome (MIM no 216550), aged 11 months to 57 years (median 27 years). All the patients had the essential features of this syndrome, i.e., typical facial and structural findings, mental retardation, microcephaly, ophthalmologic symptoms, granulocytopenia and a cheerful psychic disposition. Children with the syndrome were considered normal at birth, but upwards of 6 to 12 months, psychomotor retardation became obvious. The first symptoms were microcephaly, which manifested itself by the age of 6 months to 1 year, as well as hypotonia and delayed developmental milestones. Cohen children learned to walk at 2 to 5 years of age. Language development varied markedly. Neurological symptoms did not progress. All patients had normal EMGs. The three youngest (aged 11 months, 3 and 5 years) had normal EEGs, whereas the remainder had low-voltage EEGs. No irritative spikes or epileptoformic foci were found. Nine patients had quick beta transients. Of the 18 patients examined, 4 were profoundly, 11 severely, 1 moderately and 2 mildly retarded. On the AADM scale, Cohen patients had high scores in the positive domains, viz., self-direction, responsibility and socialisation. Maladaptive behaviour, on the other hand, was almost completely absent, except for stereotyped behaviours and odd mannerisms. Withdrawal, sexually aberrant behaviour, untrustworthy and rebellious behaviour as well as antisocial behaviour were rare. These findings are consistent with the cheerful and sociable disposition characteristic of those with Cohen syndrome.
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PMID:Neurological and psychological findings in patients with Cohen syndrome: a study of 18 patients aged 11 months to 57 years. 1056 9

Clozapine is a dibenzodiazepine derivative with established antipsychotic efficacy in adult patients with schizophrenic psychoses. There are more than 15 studies that have also demonstrated the antipsychotic efficacy of clozapine in childhood and adolescent schizophrenia. The main advantages of clozapine treatment in this age group in comparison with typical antipsychotics are: (i) high antipsychotic efficacy during an acute schizophrenic episode; (ii) better improvement in chronic cases with a high load of negative symptoms; and (iii) markedly fewer extrapyramidal adverse effects and, therefore, fairly good tolerability. However, because of its possible adverse effects on the haemopoetic system (granulocytopenia, agranulocytosis), clozapine should not be used as first-line antipsychotic medication. Other adverse effects are related to the cardiovascular system (hypotonia, tachycardia or arrhythmia), the central nervous system (epileptic seizures, fever) and liver function (transient increases in levels of hepatic transaminases). Two other frequent adverse effects are hypersalivation and body-weight gain, which may present a particular problem in adolescents and young adults. Careful monitoring of haematological parameters and other adverse effects are preconditions for a successful treatment programme.
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PMID:Management of schizophrenia in children and adolescents. The role of clozapine. 1094 14

This article elucidates the clinical picture in Cohen syndrome (MIM 216550), an autosomal recessive disorder that is overrepresented in Finland. The diagnosis is based on the typical clinical picture: nonprogressive psychomotor retardation, motor clumsiness and microcephaly, typical facial features, childhood hypotonia and hyperextensibility of the joints, ophthalmologic findings of retinochoroidal dystrophy and myopia in patients over 5 years of age, and granulocytopenia. In a nationwide study, 29 Finnish patients were investigated. Magnetic resonance images of the brain with quantitative structure analyses revealed a relatively enlarged corpus callosum (CC). The youngest patients had normal EEGs, while all others had low-voltage EEGs. Of the patients, 22% had profound, 61% severe, 6% moderate, and 11% mild retardation. In an adaptive behavior scale (AAMD), patients had high scores in the positive domains (self-direction, responsibility, and socialization), whereas maladaptive behavior was almost lacking. Only the youngest patients had unimpaired visual function. Vision started to deteriorate early but slowly. Progressive myopia and retinochoroidal dystrophy were found in all of the patients over 5 years of age. All of the patients had isolated granulocytopenia. The heart anatomy was normal. However, decreased left ventricular function with advancing age was found. No significant endocrine abnormalities were discovered. Fingers were slender but short, with a typical metacarpophalangeal pattern profile. The manifestations vary at different ages. The Finnish Cohen patients are clinically highly homogeneous, their disease gene being located on chromosome 8. Heterogeneity probably exists among other patients claimed to have Cohen syndrome.
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PMID:Cohen syndrome: essential features, natural history, and heterogeneity. 1147 3

We describe eight members from two large Amish kindreds who share a phenotype characterized by early-onset pigmentary retinopathy and myopia, global developmental delay and mental retardation, microcephaly, short stature, hypotonia, joint hyperextensibility, small hands and feet, common facial appearance, and friendly disposition. Several of the children had intermittent granulocytopenia. The phenotypic occurrence in three siblings coupled with the increased coefficient of inbreeding in the Amish suggested that this disorder is autosomal recessive and due to a single founder allele. Despite similarity to the clinical features of Cohen syndrome, experienced dysmorphologists attending the 23rd David W. Smith Workshop suggested the facial gestalt of the Amish children was inconsistent with this diagnosis. We mapped the locus responsible for these individuals' phenotype to chromosome 8q22-q23, which contains the recently discovered Cohen syndrome gene, COH1. Complete sequencing of the COH1 gene identified a likely disease-causing frameshift mutation and a missense mutation in the Amish patients. A comparison of features among different Cohen syndrome populations with shared linkage to the COH1 locus or known COH1 gene mutations may allow for the determination of improved clinical criteria on which to suspect the diagnosis of Cohen syndrome. We conclude that facial gestalt seems to be an unreliable indicator of Cohen syndrome between ethnic populations, although it is quite consistent among affected individuals within a particular ethnic group. Other features common to almost all individuals with proven COH1 mutations, such as retinal dystrophy, myopia, microcephaly, mental retardation, global developmental delay, hypotonia, and joint hyperextensibility appear to be better clinical indicators of this disorder.
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PMID:Cohen syndrome in the Ohio Amish. 1521 51