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Acrodermatitis , Desnutrición , Acrodermatitis/diagnóstico , Acrodermatitis/genética , Humanos , Zinc/deficienciaRESUMEN
OBJECTIVES: The effect of tongue cleaning on digestive power is mentioned in Ayurvedic information sources. However, no study has yet evaluated this. We aimed to evaluate the effects of tongue cleaning on digestive power from Ayurvedic viewpoint, and on oral health-related quality of life (OHRQoL) in healthy adults. DESIGN: Randomized cross-over. INTERVENTIONS: We recruited healthy adults aged 20-60 years. After randomization, the immediate intervention group started tongue cleaning with a tongue scraper every morning for 4 weeks, and then waited for 4 weeks. The delayed intervention group initially waited for 4 weeks, and then started tongue cleaning in the same way. MAIN OUTCOME MEASURES: We assessed the outcomes using the questionnaire on digestive power from Ayurvedic viewpoint, and the General Oral Health Assessment Index for OHRQoL. We estimated the effects of tongue cleaning using generalized estimating equations (GEE). We also conducted a sensitivity analysis, by comparing the changes in outcomes during the first 4 weeks of both groups. RESULTS: Of 58 participants, 57 completed the study. In GEE analysis, tongue cleaning showed improvement in some components of Ayurvedic digestive power represented by fecal and body conditions. For example, the odds ratio for improvement of constipation was 2.80 (95% CI: 1.04-7.58). The General Oral Health Assessment Index score was significantly increased by 4.33 points (95% CI: 2.18-6.48) after tongue cleaning. In sensitivity analyses, the trends of the results were similar to the main GEE analyses. CONCLUSIONS: Tongue cleaning may be an effective method to improve digestive power and OHRQoL.
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Medicina Ayurvédica , Higiene Bucal/métodos , Higiene Bucal/estadística & datos numéricos , Calidad de Vida , Adulto , Estreñimiento/epidemiología , Estreñimiento/fisiopatología , Estudios Cruzados , Digestión , Humanos , Persona de Mediana Edad , Salud Bucal , Lengua/fisiología , Adulto JovenRESUMEN
BACKGROUND: Environmental factors seem to be related to the incidence of allergic disease. Children with a later birth order are often exposed to environments, where pathogens and endotoxins can be found, and thus have a higher risk of developing infectious diseases. Therefore, birth order is regarded as an indicator that reflects post-natal environment. However, longitudinal studies are limited on this subject. This study sought to elucidate the relationships between birth order and allergic disease. METHODS: From a nationwide longitudinal study that followed children born in 2001 (n = 47 015), we selected doctors' visits for 3 types of allergic disease-bronchial asthma, food allergy and atopic dermatitis-from infancy to 12 years of age and conducted binomial log-linear regression analysis to evaluate the associations between birth order and these diseases. We adjusted for the child and parental factors and estimated risk ratio (RR) and 95% confidence interval (CI) for each outcome. RESULTS: The associations between birth order and bronchial asthma were diverse; later birth order increased the risk in early childhood, but decreased the risks during school age. For example, the adjusted RR comparing third-born or higher and first-born children was 1.19 (95% CI, 1.05-1.35) between 30 and 42 months of age, but was 0.76 (95% CI, 0.65-0.89) between 10 and 11 years. Later birth order was generally protective for food allergy but increased the risk of atopic dermatitis. CONCLUSION: The influence of birth order depended on the type of allergic disease and the childhood period. Childhood is unique in terms of physical and immunological development, and the immune response to the post-natal environment in childhood appears to be heterogeneous.
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Orden de Nacimiento , Hipersensibilidad/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Japón/epidemiología , Estudios Longitudinales , Masculino , Encuestas y CuestionariosRESUMEN
AIMS: Abnormalities in the imprinted locus on chromosome 6q24 are the most common causes of transient neonatal diabetes mellitus (6q24-related transient neonatal diabetes). 6q24-Related transient neonatal diabetes is characterized by the patient being small-for-gestational age, diabetes mellitus at birth, spontaneous remission within the first few months and frequent recurrence of diabetes after childhood. However, it is not clear whether individuals with 6q24 abnormalities invariably develop transient neonatal diabetes. This study explored the possibility that 6q24 abnormalities might cause early-onset, non-autoimmune diabetes without transient neonatal diabetes. METHODS: The 6q24 imprinted locus was screened for abnormalities in 113 Japanese patients with early-onset, non-obese, non-autoimmune diabetes mellitus who tested negative for mutations in the common maturation-onset diabetes of the young (MODY) genes and without a history of transient neonatal diabetes. Positive patients were further analysed by combined loss of heterozygosity / comparative genomic hybridization analysis and by microsatellite analysis. Detailed clinical data were collected through the medical records of the treating hospitals. RESULTS: Three patients with paternal uniparental isodisomy of chromosome 6q24 were identified. None presented with hyperglycaemia in the neonatal period. Characteristically, these patients were born small-for-gestational age, representing 27.2% of the 11 patients whose birth weight standard deviation score (SDS) for gestational age was below -2.0. CONCLUSIONS: Abnormalities in the imprinted locus on chromosome 6q24 do not necessarily cause transient neonatal diabetes. Non-penetrant 6q24-related diabetes could be an underestimated cause of early-onset, non-autoimmune diabetes in patients who are not obese and born small-for-gestational age.
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Enfermedades Autoinmunes/etiología , Trastornos de los Cromosomas/fisiopatología , Cromosomas Humanos Par 6 , Diabetes Mellitus/etiología , Adolescente , Adulto , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Índice de Masa Corporal , Niño , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Salud de la Familia , Femenino , Sitios Genéticos , Pruebas Genéticas , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Japón , Masculino , Adulto JovenRESUMEN
AIMS: To investigate the molecular and clinical characteristics of the largest series of Japanese patients with glucokinase maturity-onset diabetes of the young (GCK-MODY), and to find any features specific to Asian people. METHODS: We enrolled 78 Japanese patients with GCK-MODY from 41 families (55 probands diagnosed at the age of 0-14 years and their 23 adult family members). Mutations were identified by direct sequencing or multiplex ligation-dependent probe amplification of all exons of the GCK gene. Detailed clinical and laboratory data were collected on the probands using questionnaires, which were sent to the treating physicians.ãData on current clinical status and HbA1c levels were also collected from adult patients. RESULTS: A total of 35 different mutations were identified, of which seven were novel. Fasting blood glucose and HbA1c levels of the probands were ≤9.3 mmol/l and ≤56 mmol/mol (7.3%), respectively, and there was considerable variation in their BMI percentiles (0.4-96.2). In total, 25% of the probands had elevated homeostatic assessment of insulin resistance values, and 58.3% of these had evidence of concomitant Type 2 diabetes in their family. The HbA1c levels for adults were slightly higher, up to 61 mmol/mol (7.8%). The incidence of microvascular complications was low. Out of these 78 people with GCK-MODY and 40 additional family members with hyperglycaemia whose genetic status was unknown, only one had diabetic nephropathy. CONCLUSIONS: The molecular and clinical features of GCK-MODY in Japanese people are similar to those of other ethnic populations; however, making a diagnosis of GCK-MODY was more challenging in patients with signs of insulin resistance.
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Diabetes Mellitus Tipo 2/genética , Angiopatías Diabéticas/epidemiología , Salud de la Familia , Glucoquinasa/genética , Resistencia a la Insulina , Mutación , Enfermedades Vasculares Periféricas/complicaciones , Adulto , Anciano , Sustitución de Aminoácidos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Angiopatías Diabéticas/prevención & control , Femenino , Eliminación de Gen , Estudios de Asociación Genética , Glucoquinasa/metabolismo , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Japón/epidemiología , Masculino , Microvasos/efectos de los fármacos , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/prevención & control , Polimorfismo de Nucleótido SimpleAsunto(s)
Aborto Espontáneo/epidemiología , Terremotos , Selección Genética , Razón de Masculinidad , Femenino , Humanos , Masculino , EmbarazoRESUMEN
OBJECTIVES: Controversy remains over whether declines in male births reported after population stressors result from either or both reduced conception of males or increased selection in utero against male fetuses. We use monthly birth cohorts to determine if Japanese male births following the Great East Japan Earthquake of 2011 fell below levels expected from female births and from history (i.e., autocorrelation) among cohorts exposed to the Earthquake at or after conception. METHODS: We apply interrupted time-series methods to 69 months (i.e., April, 2006 through December, 2011) of birth data from the most and least affected prefectures as well as from the remainder of Japan. We estimate expected male births from female births and from autocorrelation. RESULTS: Findings varied by distance from the greatest damage but suggest sensitive periods both early and late in gestation when population stressors may induce selection against males in utero. Support for reduced conception of males appeared only in the prefectures most damaged by the Earthquake. CONCLUSIONS: Results align with the claim that natural selection has conserved mechanisms that reduce the odds of a male live birth during stressful times by reducing the conception of males and by increasing the rate of spontaneous abortion among male fetuses.
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Aborto Espontáneo/epidemiología , Terremotos , Selección Genética , Razón de Masculinidad , Estudios de Cohortes , Femenino , Humanos , Japón/epidemiología , Masculino , Embarazo , Estaciones del AñoAsunto(s)
Esperanza de Vida , Fumar/epidemiología , Femenino , Humanos , Japón/epidemiología , Masculino , Distribución por SexoRESUMEN
We report a case of segmental uniparental maternal hetero- and isodisomy involving the whole of chromosome 6 (mat-hUPD6 and mat-iUPD6) and a cullin 7 (CUL7) gene mutation in a Japanese patient with 3M syndrome. 3M syndrome is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth retardation that was recently reported to involve mutations in the CUL7 or obscurin-like 1 (OBSL1) genes. We encountered a patient with severe growth retardation, an inverted triangular gloomy face, an inverted triangle-shaped head, slender long bones, inguinal hernia, hydrocele testis, mild ventricular enlargement, and mild mental retardation. Sequence analysis of the CUL7 gene of the patient revealed a homozygous missense mutation, c.2975G>C. Genotype analysis using a single nucleotide polymorphism array revealed two mat-hUPD and two mat-iUPD regions involving the whole of chromosome 6 and encompassing CUL7. 3M syndrome caused by complete paternal iUPD of chromosome 6 involving a CUL7 mutation has been reported, but there have been no reports describing 3M syndrome with maternal UPD of chromosome 6. Our results represent a combination of iUPDs and hUPDs from maternal chromosome 6 involving a CUL7 mutation causing 3M syndrome.
Asunto(s)
Cromosomas Humanos Par 6/genética , Proteínas Cullin/genética , Enanismo/genética , Discapacidad Intelectual/genética , Hipotonía Muscular/genética , Disomía Uniparental/genética , Preescolar , Femenino , Humanos , Masculino , Mutación Missense , Columna Vertebral/anomalíasRESUMEN
OBJECTIVE: We aimed to investigate recent trends in prescriptions for the treatment of paediatric gastroenteritis in Japan over a 10-year period (1997-2007). METHODS: In this retrospective cohort study, we collected data for 2295 prescriptions for 1241 putative cases of paediatric gastroenteritis, which were treated between 1997 and 2007 at Hamamatsu University Hospital, Hamamatsu, Japan. RESULTS: The most frequently prescribed drugs were probiotics (n = 621), followed by anti-emetics (n = 474). In most years between 1997 and 2007, more cases were treated with probiotics than with any other drug type (30.6-63.3% of cases), with the percentage increasing between 2005 and 2007. In contrast, the frequencies of anti-emetic and antipyretic prescriptions remained fairly stable, and prescriptions for antibiotics decreased slightly over the study period. Anti-emetics were commonly used in this hospital. CONCLUSION: Although experimental evidence upon which to base recommendations is lacking, Japanese evidence-based guidelines are critical for improving the quality of treatment of paediatric gastroenteritis.
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Prescripciones de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/tendencias , Gastroenteritis/tratamiento farmacológico , Virosis/tratamiento farmacológico , Envejecimiento , Analgésicos no Narcóticos/uso terapéutico , Antibacterianos/uso terapéutico , Antieméticos/uso terapéutico , Preescolar , Estudios de Cohortes , Vías de Administración de Medicamentos , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Lactante , Japón , Masculino , Probióticos/uso terapéutico , Estudios RetrospectivosRESUMEN
OBJECTIVE: LHX4, a LIM-homeodomain transcription factor, is required for development of the pituitary and nervous system. Several mutations of the LHX4 gene have been identified in patients with combined pituitary hormone deficiency (CPHD). The objective of the study was to clarify the molecular basis of a Japanese patient of CPHD with a small anterior pituitary and an ectopic posterior pituitary. METHODS: Genomic DNA was extracted from blood samples of the patient. Exons and exon-intron junctions of the LHX4 gene were amplified and sequenced. An expression vector of the mutant LHX4 protein was constructed and its function was analyzed in vitro. RESULTS: A novel missense mutation (V101A) was identified. IN VITRO transfection studies demonstrated that V101A mutant LHX4 was unable to activate the POU1F1 and FSHbeta subunit gene promoter, indicating a loss of function mutation. CONCLUSION: Our results identify a novel loss of function mutation of the LHX4 gene in a Japanese patient with CPHD.
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Proteínas de Homeodominio/genética , Hipopituitarismo/genética , Mutación Missense , Hormonas Adenohipofisarias/deficiencia , Hormonas Neurohipofisarias/deficiencia , Factores de Transcripción/genética , Adolescente , Secuencia de Aminoácidos , Hormona Folículo Estimulante de Subunidad beta/genética , Hormona del Crecimiento/uso terapéutico , Humanos , Hidrocortisona/uso terapéutico , Hipopituitarismo/tratamiento farmacológico , Proteínas con Homeodominio LIM , Masculino , Datos de Secuencia Molecular , Testosterona/uso terapéutico , Tiroxina/uso terapéutico , Factor de Transcripción Pit-1/genética , Activación TranscripcionalRESUMEN
Three patients with the severe form of propionic acidaemia were treated with living-donor liver transplantation (LDLT). The procedure was successful for all patients and the incidence of metabolic decompensation was reduced dramatically even without protein restriction. Biochemically, however, the improvement was not significant and the patients continued to excrete large amounts of propionic acid metabolites. One of the patients experienced a severe acidaemic episode 3 years after transplantation. LDLT has a beneficial effect on the care of severely affected patients since it reduces the risk of metabolic decompensation and improves the quality of life with less strict dietary control. Adequate protein restriction and medication need to be maintained even after successful transplantation.
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Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/cirugía , Trasplante de Hígado , Donadores Vivos , Propionatos/metabolismo , Niño , Desarrollo Infantil , Preescolar , Femenino , Humanos , Lactante , Masculino , Complicaciones Posoperatorias , Acidemia PropiónicaRESUMEN
Propionic acidaemia (PCCD) or deficiency of propionyl-CoA carboxylase (PCC) is one of the most common organic acidaemias. Recent studies have suggested that this disease can cause somatic or cognitive deterioration even in patients without ketosis or metabolic acidosis, or in cases with unusually late onset. This suggests that for this disease a sensitive yet practical screening procedure is required to achieve early treatment. We conducted a pilot study of gas chromatographic-mass spectrometric screening of 12,000 newborns for PCCD using eluates from dried filter-paper urine collected at 4-7 days of age. Methylcitrate (MC) was targeted for PCCD. For bulk screening, 2-hydroxyundecanoate was used as internal standard; for quantification, stable-isotope-labelled MC was used. Urease pretreatment without fractionation allowed satisfactory recovery and reproducibility of the highly polar MC. We detected an asymptomatic male infant with distinctly elevated MC: the creatinine-corrected level relative to 2-hydroxyundecanoate was 4.8 SD above the normal mean. The MC concentration calculated using the stable-isotope-labelled internal standard was 70.6 mmol/mol creatinine 14.7 SD above the normal mean of 3.70. Parallel analysis of the dried blood spot at 4 days of age by tandem MS showed only borderline elevation of propionylcarnitine. The activity of PCC in lymphocytes was 7% of control. Gene analysis revealed that a single missense mutation, TAT to TGT, resulting in Y435C in the beta chain was present in a homozygous form. Dietary treatment including carnitine supplementation decreased this infant's MC level and to date (at 13 months of age), he shows no neurological or somatic abnormalities.
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Carboxiliasas/deficiencia , Carnitina/análogos & derivados , Citratos/orina , Cromatografía de Gases y Espectrometría de Masas , Tamizaje Neonatal , Papel , Propionatos/sangre , Carboxiliasas/genética , Carnitina/sangre , Análisis Mutacional de ADN , Homocigoto , Humanos , Recién Nacido , Masculino , Espectrometría de Masas , Metilmalonil-CoA Descarboxilasa , Mutación MissenseAsunto(s)
Proteínas de Unión al ADN/genética , Proteínas Nucleares , Factores de Transcripción , Síndrome de Turner/genética , Cromosoma Y/genética , ADN/química , ADN/genética , Análisis Mutacional de ADN , Femenino , Humanos , Cariotipificación , Aberraciones Cromosómicas Sexuales , Proteína de la Región Y Determinante del Sexo , Síndrome de Turner/patologíaRESUMEN
Although clinical features of Turner syndrome have primarily been explained by the dosage effects of SHOX (short stature homeobox-containing gene) and the putative lymphogenic gene together with chromosomal effects leading to nonspecific features, several matters remain to be determined, including modifying factors for the effects of SHOX haploinsufficiency, chromosomal location of the lymphogenic gene, and genetic factors for miscellaneous features such as multiple pigmented nevi. To clarify such unresolved issues, we examined clinical findings in 47 patients with molecularly defined Xp deletion chromosomes accompanied by the breakpoints on Xp21-22 (group 1; n = 19), those accompanied by the breakpoints on Xp11 (group 2; n = 16), i(Xq) or idic(X)(p11) chromosomes (group 3; n = 8), and interstitial Xp deletion chromosomes (group 4; n = 4). The deletion size of each patient was determined by fluorescence in situ hybridization and microsatellite analyses for 38 Xp loci including SHOX, which was deleted in groups 1-3 and preserved in group 4. The mean GH-untreated adult height was -2.2 SD in group 1 and -2.7 SD in group 2 (GH-untreated adult heights were scanty in group 3). The prevalence of spontaneous breast development in patients aged 12.8 yr or more (mean +/- 2 SD for B2 stage) was 11 of 11 in group 1, 7 of 12 in group 2, and 1 of 7 in group 3. The prevalence of wrist abnormality suggestive of Madelung deformity was 8 of 18 in group 1 and 2 of 23 in groups 2 and 3, and 9 of 18 in patients with spontaneous puberty and 1 of 23 in those without spontaneous puberty. The prevalence of short neck was 1 of 19 in group 1 and 7 of 24 in groups 2 and 3. Soft tissue and visceral anomalies were absent in group 1 preserving the region proximal to Duchenne muscular dystrophy and were often present in groups 2 and 3 missing the region distal to monoamine oxidase A (MAOA). Multiple pigmented nevi were observed in groups 1-3, with the prevalence of 0 of 7 in patients less than 10 yr of age and 15 of 36 in those 10 yr or older regardless of the presence or absence of spontaneous puberty. Turner phenotype was absent in group 4, including a fetus aborted at 21 wk gestation who preserved the region distal to MAOA. The results provide further support for the idea that clinical features in X chromosome aberrations are primarily explained by haploinsufficiency of SHOX and the lymphogenic gene and by the extent of chromosome imbalance in mitotic cells and pairing failure in meiotic cells. Furthermore, it is suggested that 1) expressivity of SHOX haploinsufficiency in the limb and faciocervical regions is primarily influenced by gonadal function status and the presence or absence of the lymphogenic gene, respectively; 2) the lymphogenic gene for soft tissue and visceral stigmata is located between Duchenne muscular dystrophy and MAOA; and 3) multiple pigmented nevi may primarily be ascribed to cooperation between a hitherto unknown genetic factor and an age-dependent factor other than gonadal E.
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Eliminación de Gen , Síndrome de Turner/genética , Cromosoma X/genética , Adulto , Aberraciones Cromosómicas , Femenino , Crecimiento/fisiología , Mano/crecimiento & desarrollo , Deformidades de la Mano/genética , Proteínas de Homeodominio/genética , Humanos , Cariotipificación , Ovario/fisiopatología , Trastornos de la Pigmentación/genética , Radiografía , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína de la Caja Homeótica de Baja Estatura , Síndrome de Turner/diagnóstico por imagen , Síndrome de Turner/fisiopatologíaRESUMEN
Ehlers-Danlos syndrome type IV is of special interest to neurologists because of the risk of cerebrovascular complications. We describe a 5-year-old female with Ehlers-Danlos syndrome type IV, demonstrating multiple intracranial aneurysms and right middle cerebral artery stenosis. The diagnosis of Ehlers-Danlos syndrome type IV was confirmed by electron microscopic examination of a skin biopsy. To our knowledge, this is the youngest reported patient with intracranial aneurysms associated with the Ehlers-Danlos syndrome type IV. Ehlers-Danlos syndrome type IV should be considered in the differential diagnosis of cerebrovascular disorder and stroke in early childhood.
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Síndrome de Ehlers-Danlos/diagnóstico , Aneurisma Intracraneal/etiología , Arteria Cerebral Media/patología , Piel/patología , Edad de Inicio , Biopsia , Trastornos Cerebrovasculares/diagnóstico , Preescolar , Constricción Patológica , Diagnóstico Diferencial , Síndrome de Ehlers-Danlos/complicaciones , Síndrome de Ehlers-Danlos/patología , Femenino , Humanos , Aneurisma Intracraneal/patología , Angiografía por Resonancia MagnéticaRESUMEN
A liver transplantation from an asymptomatic mother, who was a carrier of ornithine transcarbamylase deficiency, to her daughter, who had severe manifestation, was successfully performed. One-year monitoring of plasma amino acid and urinary orotate/orotidine levels revealed no abnormality in the urea cycle in either subject.
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Heterocigoto , Trasplante de Hígado , Donadores Vivos , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/cirugía , Uridina/análogos & derivados , Adulto , Aminoácidos/sangre , Niño , Femenino , Humanos , Ácido Orótico/orina , Resultado del Tratamiento , Uridina/orinaRESUMEN
Aminopropionaldehyde dehydrogenase was purified to apparent homogeneity from 1,3-diaminopropane-grown cells of Arthrobacter sp. TMP-1. The native molecular mass and the subunit molecular mass of the enzyme were approximately 20,5000 and 52,000, respectively, suggesting that the enzyme is a tetramer of identical subunits. The apparent Michaelis constant (K(m)) for 1,3-diaminopropane was approximately 3 microM. The enzyme equally used both NAD(+) and NADP(+) as coenzymes. The apparent K(m) values for NAD(+) and NADP(+) were 255 microM and 108 microM, respectively. The maximum reaction rates (V(max)) for NAD(+) and NADP(+) were 102 and 83.3 micromol min(-1) mg(-1), respectively. Some tested aliphatic aldehydes and aromatic aldehydes were inert as substrates. The optimum pH was 8.0-8.5. The enzyme was sensitive to sulfhydryl group-modifying reagents.
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Aldehído Oxidorreductasas/aislamiento & purificación , Aldehído Oxidorreductasas/metabolismo , Arthrobacter/enzimología , Aldehído Oxidorreductasas/química , Aldehídos/metabolismo , Diaminas/metabolismo , Inhibidores Enzimáticos/farmacología , Represión Enzimática , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Cinética , Peso Molecular , NAD/metabolismo , NADP/metabolismo , Subunidades de Proteína , Especificidad por Sustrato , Temperatura , Ácido p-Cloromercuribenzoico/farmacologíaRESUMEN
Deficiency of mitochondrial 3-hydroxy-3-methylglutaryl CoA lyase (HL, EC4.1.3.4.) is an autosomal recessive genetic disorder characterized by acute episodes of vomiting, hypotonia, and lethargy in the neonatal period or in infancy. Except in Saudi Arabia, where HL deficiency is the most common organic acidemia, the disorder is quite rare with only 41 cases being reported in the English literature, and only five known cases among Japanese. In this study, we present the results of a molecular analysis of all five Japanese patients together with their clinical phenotypes. Five different mutations in the HL gene were identified: one large deletion, one nonsense mutation, one missense mutation, and two splice mutations. Except for G835A (E279K) with its relatively common occurrence among Japanese, these mutations were unique to each family. The results of expression studies with mutated HL cDNAs confirmed the pathogenicity of these mutations and supported the importance of previously identified functional domains of the HL molecule, i.e., the putative catalytic site or dimerization site. In addition, we identified an alternative splicing event that resulted in the skipping of exons 5 and 6. This alternatively spliced product did not show HL activity and was present in various tissues of normal subjects. Clinically, all patients presented with similar symptoms, except that the timing of the initial presentation varied considerably, from 1 day to 1 year 3 months. In general, patients with null-activity mutations presented earlier in life, whereas those with residual activities presented later.
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Mutación , Oxo-Ácido-Liasas/deficiencia , Oxo-Ácido-Liasas/genética , Edad de Inicio , Empalme Alternativo , Secuencia de Bases , Análisis Mutacional de ADN , Cartilla de ADN/genética , Femenino , Expresión Génica , Vectores Genéticos , Humanos , Lactante , Recién Nacido , Masculino , Biología Molecular , Fenotipo , Mutación Puntual , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Eliminación de Secuencia , TransfecciónRESUMEN
We reported a 15-year-old boy with idiopathic hypoparathyroidism who presented with paroxysmal kinesigenic choreoathetosis at age 10. Calcium levels were low and intact parathyroid hormones were undetectable in serum. Computed tomography showed calcifications in the basal ganglia, thalamus, and cerebral white matter. He had a history of infantile convulsions with a benign outcome. The convulsions occurred in clusters at age 2.5 months, but they never recurred. This patient's clinical features were phenotypically indistinguishable from those of infantile convulsions and choreoathetosis (ICCA) syndrome