RESUMEN
Fabry disease results from deficiency of the lysosomal enzyme alpha-galactosidase A. The families of 11 index cases were screened by enzyme and molecular assays. Further clinical and laboratory investigations were carried out in all cases. Including 33 new patients, a total of 28 females (Age 25,82⯱â¯12,1 Range 8-46) and 16 males (Age 24,56⯱â¯15,04 Range 2-48) were investigated. Ten different disease-causing variants were found two of them being novel. One patient had co-existing familial mediteranian fever, one had celiac disease and three had rheumatological disorders. Lipoprotein (a) levels were elevated in 17,6%, homocysteine in 22,2%, total and low density cholesterol in 12% and antithrombin 3 levels were elevated in 13,3%. One patient was found to be heterozygous for prothrombin p.G20210A disease-causing variant (5,8%) and two for factor V Leiden disease-causing variant (11,7%). Anticardiolipin IgM antibody was found to be positive in 11,7%. The patients with abnormal cranial imaging were also noticed to have additional risk factors for thrombosis. This study provides the largest data about Fabry patients from Turkey and implies that co-existing risk factors unrelated to Fabry Disease have significant association with the presence of clinical symptoms in females and might cause an early and severe clinical course in males.
Asunto(s)
Biomarcadores/metabolismo , Enfermedad de Fabry/epidemiología , Enfermedad de Fabry/metabolismo , Variación Genética , alfa-Galactosidasa/metabolismo , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudios de Seguimiento , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Pronóstico , Factores de Riesgo , Turquía/epidemiología , Adulto Joven , alfa-Galactosidasa/genéticaRESUMEN
Inherited metabolic diseases are pathologic conditions that generally develop as a result of impairment of the production or breakdown of protein, carbohydrate, and fatty acids. Early determination of hematological findings has a positive effect on the prognosis of metabolic diseases. Three hundred eighteen patients who were being followed-up within the previous 6 months at Department of Pediatric Nutrition and Metabolism, Gazi University, Turkey, were included in the study. The hematological findings were classified under 7 main groups: anemia of chronic disease, iron deficiency anemia, vitamin B12 deficiency anemia, hemophagocytosis, leukocytosis, and thrombocytosis. Nine hundred twenty-two hematological examinations of the 319 patients were included in the study, and 283 hematological findings were determined, 127 anemia of chronic disease, 81 iron deficiency anemia, 56 cytopenia, and 4 vitamin B12 deficiency anemia. Leukocytosis (n=1), thrombocytosis (n=5), and hemophagocytosis (n=9) were also observed. It was determined that, although anemia of chronic disease and nutritional anemia are the most common hematological findings, these may be diagnosed late, whereas neutropenia, thrombocytopenia, pancytopenia, and hemostasis disorders may be diagnosed earlier. Our study is the most comprehensive one in the literature, and we think it would positively contribute to the monitoring and prognosis of congenital metabolic diseases.
Asunto(s)
Enfermedades Hematológicas/epidemiología , Enfermedades Hematológicas/etiología , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/epidemiología , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Lactante , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Subclinical micronutrient deficiencies have been gradually becoming more important as a public health problem and drawing attention of the health authorities. Today it has been known that detecting and treating people having deficiency symptoms alone is no longer sufficient. It is important to detect and prevent any deficiency before it displays clinical manifestations. Zinc deficiency is one of the most widespread micronutrient deficiencies. In this study, we aimed to evaluate the zinc status and the associated factors in healthy school-age children. METHODS: The study was carried out in schools in Altindag, the district of Ankara. A total of 1063 healthy children, 585 girls and 478 boys, aged 5-16 years were included in the study. Serum zinc, high-sensitivity C-reactive protein levels and white blood cell count were measured. A serum zinc level <65 µg/dL was considered as subclinical zinc deficiency for children <10 years of age. For children ≥10 years of age the cutoffs for serum zinc concentration were set at 66 µg/dL for females and 70 µg/dL for males. A questionnaire was developed to collect socioeconomic and demographic information of the participants. RESULTS: The prevalence of subclinical zinc deficiency in children attending the study was detected to be 27.8%. This high ratio showed zinc deficiency was an important health problem in the Altindag district of Ankara, Turkey. CONCLUSIONS: Evaluating the indicators of zinc deficiency such as serum zinc concentration, dietary zinc intake and stunting prevalence, this study is the most comprehensive epidemiological study performed in children in Turkey. This study reveals the high prevalence of subclinical zinc deficiency and indicates that zinc deficiency is a public health concern for the study population.
Asunto(s)
Enfermedades Carenciales/epidemiología , Enfermedades Desatendidas/epidemiología , Zinc/deficiencia , Adolescente , Distribución de Chi-Cuadrado , Niño , Preescolar , Enfermedades Carenciales/diagnóstico , Femenino , Encuestas Epidemiológicas , Humanos , Incidencia , Masculino , Evaluación de Necesidades , Estado Nutricional , Medición de Riesgo , Población Rural , Factores Socioeconómicos , Turquía/epidemiología , Zinc/sangreRESUMEN
Osteopetrosis is a rare genetic condition of reduced osteoclastic bone resorption which causes defective bone remodeling and skeletal sclerosis during growth, having effects on many organs and tissues. Mutation of T-cell immune regulator 1 (TCRG1) gene is the most common genetic defect leading to osteopetrosis, with poor prognosis. The autosomal recessive form presents in the infantile period (also known as malignant infantile osteopetrosis--MIOP), and is characterized by fractures, short stature, hepatosplenomegaly, compressive neuropathies, hypocalcemia and pancytopenia. Being a rare disease with non-specific clinical manifestations, the diagnosis is difficult and usually delayed. Rickets is a characteristic feature of MIOP which results from the defect in osteoclasts to provide a normal Ca/P balance resulting in the poor mineralization of the osteoid. Various treatment options have been suggested for osteopetrosis, but hematopoietic stem cell transplantation still remains the only curative treatment option presently. The authors report the case of a 46-day-old girl with late-onset neonatal hypocalcemia and rickets that was later diagnosed as osteopetrosis. This case report emphasizes that infantile osteopetrosis is an important cause of neonatal hypocalcemia. As irreversible complications develop within the first months of life, immediate diagnosis and early intervention are crucial and may be life-saving.
Asunto(s)
Hipocalcemia/complicaciones , Osteopetrosis/diagnóstico , Raquitismo/complicaciones , Conservadores de la Densidad Ósea/uso terapéutico , Calcitriol/uso terapéutico , Femenino , Humanos , Lactante , Osteopetrosis/complicaciones , Osteopetrosis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
We aimed to investigate the diagnostic utility of serum DPP-IV enzyme activity, urinary GAG/Cre ratio, chitotriosidase activity, total adenosine deaminase (ADA) and ADA-1 isoenzyme activity in the diagnosis of MPS. 31 MPS patients which were previously diagnosed by clinical and enzymatic analysis and 31 healthy controls matched with age and gender were included in this study. Serum DPP-IV enzyme activity, urinary GAG/Cre ratio, total ADA and ADA-1 isoenzyme activity were significantly higher in patients than in controls (p<0.001, p<0.001, p=0.038 and p=0.006, respectively). There were significant correlations between serum DPP-IV enzyme activity and urinary GAG/Cre ratios, ADA-1 activity, ADA-1/total ADA (r=0.498, p<0.001; r=0.348, p=0.006; r=0.270, p=0.034, respectively). Area under ROC curve for DPP-IV enzyme activity was 0.988, p<0.001 and for urinary GAG/Cre ratio was 0.986, p<0.001. DPP-IV enzyme activity and urinary GAG/Cre ratio were the most significant parameters according to the univariate logistic regression analysis (p=0.001 and p<0.001, respectively). The measurement of serum DPP-IV enzyme activity can be used complementary to the urinary GAG/Cre ratio for first-line MPS screening, since it is more less prone to age and hydration related interferences.
Asunto(s)
Dipeptidil Peptidasa 4/sangre , Mucopolisacaridosis/sangre , Mucopolisacaridosis/diagnóstico , Adenosina Desaminasa/sangre , Adolescente , Niño , Creatinina/orina , Diagnóstico Precoz , Femenino , Glicosaminoglicanos/orina , Hexosaminidasas/sangre , Humanos , Isoenzimas/sangre , Masculino , Mucopolisacaridosis/enzimología , Reproducibilidad de los ResultadosRESUMEN
GRACILE syndrome is a rare autosomal recessive disease characterized by fetal growth retardation, Fanconi type aminoaciduria, cholestasis, iron overload, profound lactic acidosis, and early death. It is caused by homozygosity for a missense mutation in the BCS1L gene. The BCS1L gene encodes a chaperone responsible for assembly of respiratory chain complex III. Here we report that a homozygous mutation c.296C > T (p.P99L), in the first exon of BCS1L gene found in an affected 2-month-old boy of asymptomatic consanguineous parents results in GRACILE syndrome. This genotype is associated with a severe clinical presentation. So far no available treatments have changed the fatal course of the disease, and the metabolic disturbance responsible is still not clearly identified. Therefore, providing prenatal diagnosis in families with previous affected infants is of major importance. Mitochondrial disorders are an extremely heterogeneous group of diseases sharing, in common, the fact that they all ultimately impair the function of the mitochondrial respiratory chain. A clinical picture with fetal growth restriction, postnatal lactacidosis, aminoaciduria, hypoglycemia, coagulopathy, elevated liver enzymes, and cholestasis should direct investigations on mitochondrial disorder.
Asunto(s)
Acidosis Láctica/genética , Colestasis/genética , Complejo III de Transporte de Electrones/genética , Retardo del Crecimiento Fetal/genética , Hemosiderosis/genética , Errores Innatos del Metabolismo/genética , Enfermedades Mitocondriales/congénito , Aminoacidurias Renales/genética , ATPasas Asociadas con Actividades Celulares Diversas , Humanos , Lactante , Masculino , Enfermedades Mitocondriales/genética , Mutación MissenseRESUMEN
Early diagnosis for metabolic encephalopathy caused by inborn errors of metabolism is very important for the initiation of early treatment and also for prevention of sequela. Metabolic encephalopathy in the form of seizures can result from many inborn errors of metabolism and considering the large number of disorders causing metabolic encephalopathy, enzyme assays or conventional molecular tests are expensive and take considerably long period of time which results in delayed treatment. In our center we have used next generation DNA sequencing technology as an initial diagnostic test to look for about 700 disorders at the same time for the etiologic diagnosis of a 4-month-old female infant suffering from intractable seizures. The patient was found to have glycine encephalopathy resulting from a previously defined mutation in the GLDC gene. The diagnostic result was obtained much sooner than other conventional investigations. Up to our knowledge, this would be the first case with glycine encephalopathy in the literature who was approached by this novel panel method initially. Although currently, classical evaluation methods such as physical examination, biochemical and conventional molecular investigations are still accepted as the gold standards to clarify the etiology of the metabolic encephalopathy it is obvious that next generation sequence analysis will play a very significant role in the future.
Asunto(s)
Glicina-Deshidrogenasa (Descarboxilante)/genética , Hiperglicinemia no Cetósica/diagnóstico , Mutación Missense , Mutación Puntual , Análisis de Secuencia de ADN/métodos , Secuencia de Bases , Análisis Mutacional de ADN/métodos , Femenino , Genes Recesivos , Glicina/sangre , Glicina/líquido cefalorraquídeo , Glicina-Deshidrogenasa (Descarboxilante)/deficiencia , Homocigoto , Humanos , Hiperglicinemia no Cetósica/enzimología , Hiperglicinemia no Cetósica/genética , Hiperglicinemia no Cetósica/metabolismo , Lactante , Datos de Secuencia Molecular , Convulsiones/etiología , Alineación de Secuencia , Homología de Secuencia de Ácido NucleicoRESUMEN
BACKGROUND & AIMS: Vitamin A deficiency (VAD) is one of the most widespread vitamin deficiencies. Vitamin A is essential for children in order to ensure a healthy life span and sustain the normal growth and development. Aim of this study is to examine vitamin A status, and factors associated with it, in healthy school-age children. METHODS: The study was carried out in schools in Altindag, the district of Ankara, from April to May 2009. 585 girls and 478 boys, a total of 1063 healthy children aged 5-16 years were taken into the study. Serum retinol, ferritin and hs-CRP levels and complete blood count of each case were measured. A questionnaire was developed to collect socio-economic and demographic information of the participants. RESULTS: Any subclinical VAD (SRL <0.7 µmol/L) was not detected in the children attending the study. However, SRLs were suboptimal in 2.2% of cases and these children were under a high risk of developing subclinical, and subsequently clinical VAD. There were significant positive correlations between serum retinol and hemoglobin values, and statistically significant negative correlation between serum retinol level and ferritin and hsCRP. CONCLUSIONS: Vitamin A deficiency does not constitute an important public health problem for Altindag, Ankara, Turkey. Frequency of such vitamin deficiencies should be revealed before launching nationwide public health programs to fight with these deficiencies.
Asunto(s)
Estado Nutricional , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiología , Vitamina A/sangre , Adolescente , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Femenino , Ferritinas/sangre , Hemoglobinas/metabolismo , Humanos , Recuento de Leucocitos , Masculino , Factores Socioeconómicos , Encuestas y Cuestionarios , Turquía , Vitamina A/administración & dosificación , Deficiencia de Vitamina A/diagnósticoRESUMEN
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by the deficiency of hydrolases involved in the degradative pathway of glycosaminoglycans. In MPS, upper airway obstruction may result from multiple causative factors which may impact severely upon morbidity and mortality. METHODS: We evaluated upper airway obstructive disease and related clinical findings through home sleep study in 19 patients (11 with MPS VI, 4 with MPS I, 4 with MPS II) with MPS followed at Gazi University Pediatric Metabolic Unit. Patients underwent home-based sleep measurements, and sleep respiratory problems were asked in a detailed clinical history. Measurements of apnea, apnea-hypopnea index (AHI), hypopnea index, oxygen desaturation index, and minimal oxygen saturation were obtained through home sleep study. RESULTS: For 19 children, the disorder was normal in 1, mild (AHI=1.5-5/h) in 5, moderate (AHI=5-10/h) in 2, and severe (AHI>10/h) in 11. The prevalence of OSA was 94.7 % (18/19) in patients with MPS. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. Echocardiograms showed evidence of pulmonary hypertension in 13 patients. CONCLUSION: Home sleep study is a quick and accessible screening test to determine the abnormalities of breathing during sleep and enables clinicians to take necessary action for patients with severe manifestations.
Asunto(s)
Servicios de Atención de Salud a Domicilio , Mucopolisacaridosis II/diagnóstico , Mucopolisacaridosis II/epidemiología , Mucopolisacaridosis I/diagnóstico , Mucopolisacaridosis I/epidemiología , Mucopolisacaridosis VI/diagnóstico , Mucopolisacaridosis VI/epidemiología , Polisomnografía , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Adolescente , Obstrucción de las Vías Aéreas/diagnóstico , Obstrucción de las Vías Aéreas/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Tamizaje Masivo , Polisomnografía/instrumentación , TurquíaRESUMEN
For inborn errors of metabolism, high resolution melting analysis (HRMA) is a rapid, efficient, simple, and inexpensive method for mutation/rare variant screening. HRMA is a recent molecular technique for genotyping single-nucleotide polymorphisms without using probes. Here we apply HRMA to the α-galactosidase a (GLA) and glucose-6-phosphatase-alpha (G6PC) genes for mutation detection of patients with Fabry disease (MIM 301500) and glycogen storage disease type 1A (GSD1A; MIM 232200), respectively. To evaluate the procedure, genomic DNAs were blindly tested for known GLA mutations (c.658C>T, c. 679C>T, c.772G>A, c.796G>A, or c.718-719delAA) in three affected males and two obligate heterozygotes with Fabry disease, a G6PC mutation (c.247C>T) in a patient homozygous for that lesion, and 10 healthy control Turkish individuals. HRMA clearly detected the mutant amplicons and discriminated them from all wild-type GLA or G6PC amplicons. HRMA proved to be a sensitive, specific, and cost-effective mutation screening method for the rapid molecular diagnosis of these inborn errors of metabolism, indicating that the technique can be readily adapted to other genetic diseases.
Asunto(s)
Enfermedad de Fabry/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Patología Molecular , Estudios de Casos y Controles , Enfermedad de Fabry/genética , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Heterocigoto , Humanos , Masculino , Mutación Missense , Polimorfismo de Nucleótido SimpleRESUMEN
Very early onset Toni-Debré-Fanconi Syndrome, a disorder of proximal renal tubules of the kidney which results in the increased urinary excretion of glucose, amino acids, uric acid, phosphate and bicarbonate, could be the manifestation of various inborn errors. Defects of oxidative phosphorylation are a heterogeneous group of disorders with various clinical presentations. Recently, patients with early liver failure, renal tubulopathy and encephalopathy due to the mutations in the BCS1L gene coding for a structural protein in mitochondrial complex III have been described. Ten-day-old female newborn was referred to our clinic because of intractable acidosis. Physical examination revealed severe hypotonia, and hepatomegaly. The laboratory examinations revealed lactic acidosis, increased blood alanine, alanine aminotransferase and aspartate aminotransferase levels, generalized aminoaciduria and glucosuria. The tubular reabsorption of phosphate was reduced. Because of multisystem involvement, mitochondrial disease was suspected and the mutational analysis of the BCS1L gene revealed homozygous P99L mutation. As the patient was unresponsive to bicarbonate replacement, oral dichloroacetate and peritoneal dialysis, continuous high dose intravenous sodium bicarbonate therapy with a dose up to 1.25 mEq/kg/h was started. The patient got on well until the age of 9 months when she died of sepsis. It was stressed that high dose intravenous continuous sodium bicarbonate therapy could be an alternative treatment option in patients with severe acidosis and renal tubulopathy resistant to dichloroacetate and peritoneal dialysis. Patients with BCS1L mutations should be considered in the differential diagnosis of severe tubulopathy in the newborn period.
Asunto(s)
Complejo III de Transporte de Electrones/genética , Síndrome de Fanconi/diagnóstico , ATPasas Asociadas con Actividades Celulares Diversas , Consanguinidad , Síndrome de Fanconi/genética , Síndrome de Fanconi/terapia , Resultado Fatal , Femenino , Humanos , Recién Nacido , Infecciones por Pseudomonas/diagnóstico , Sepsis/diagnósticoRESUMEN
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys, resulting in hepatomegaly and renomegaly. Human chitotriosidase is a recently described fully active chitinase expressed by activated macrophages. Marked elevation of chitotriosidase activity was initially observed in plasma of patients with Gaucher disease. Subsequently, elevation was also observed in various lysosomal storage disorders such as fucosidosis, galactosialidosis and glycogen storage disease type IV. The aim of the present study was to evaluate plasma chitotriosidase activity in 19 children with glycogen storage disease type I. Plasma chitotriosidase levels were found to be significantly higher in children with GSD type I than healthy age-matched controls (21.3 ± 16.4 vs. 12.3 ± 8.9 nmol/h/mL, p=0.04). All the patients reported here presented with hepatomegaly. Our report expands the spectrum of disorders that should be included in the differential diagnosis of patients with increased plasma chitotriosidase activity, irrespective of the mechanisms involved.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo I/fisiopatología , Hexosaminidasas/sangre , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/sangre , Humanos , Lactante , Masculino , Adulto JovenRESUMEN
BACKGROUND: Chronic renal failure (CRF) is a serious complication of Fabry disease (FD). The aims of the present study were to determine the prevalence of unrecognized FD in Turkish hemodialysis population and to investigate the molecular background. METHOD: Primarily, α-galactosidase A (α-Gal A) activity was investigated on DBS in 1136 patients of both sexes who underwent dialysis for CRF in Turkey. The disease was confirmed by analyzing enzyme activity in leukocyte and GLA gene sequencing in all patients in whom α-Gal A level was 40% of normal or less. RESULTS: Mean age of the patients (44.5% female, 52.5% male) was 56.46±15.85 years. Enzyme activity was found low with DBS method in 12 patients (four males, eight females). Two men, but no women, were diagnosed with FD by enzymatic and molecular analysis. In consequence of genetic analysis of a case, a new mutation [hemizygote c.638C>T (p.P214S) missense mutation in exon 5] was identified, which was not described in literature. Family screening of cases identified six additional cases. CONCLUSION: As a result of this initial screening study performed on hemodialysis patients for the first time with DBS method in Turkey, the prevalence of FD was detected as 0.17%. Although the prevalence seems to be low, screening studies are of great importance for detecting hidden cases as well as for identifying other effected family members.
Asunto(s)
Enfermedad de Fabry/genética , Fallo Renal Crónico/genética , alfa-Galactosidasa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Estudios de Casos y Controles , Análisis Mutacional de ADN , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/epidemiología , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Hemicigoto , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Mutación Puntual , Prevalencia , Diálisis Renal , Turquía/epidemiología , Adulto JovenRESUMEN
Familial hypercholesterolemia is a genetic disorder that leads to severe atherosclerosis related cardiovascular complications in young adults. Extracorporeal elimination is a method of LDL-lowering procedures effective in patients with homozygous or severe heterozygous FH utilized in cases. The recruitment of leucocytes into the arterial intima is dependent on a cascade of events mediated through a diverse family of adhesion molecules. Several pro-inflammatory adhesion molecules are cleared by various lipid apheresis methods. This study showed that, LDL-apheresis led to several changes in circulating inflammatory factors which induced antiinflammatory and antiatherogenic changes in the plasma profile in homozygous familial hypercholesterolemic patients.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , LDL-Colesterol/sangre , Citocinas/metabolismo , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Adolescente , Aterosclerosis , Niño , Femenino , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Inflamación , Lipoproteínas LDL/metabolismo , MasculinoRESUMEN
OBJECTIVES: Children with obesity have a high cardiovascular risk and an impaired oxidant-antioxidant status, which may lead to endothelial dysfunction and increased carotid intima media thickness (IMT) even in childhood. The aim of this study was to investigate the circulating oxidized low-density lipoprotein (LDL) concentrations and the IMT of carotid arteries in prepubertal obese children, and also to search for its possible association with carotid atherosclerosis. METHODS: Twenty-seven prepubertal obese children (age, 7.48±2.05 years; boys, 59%) and 30 healthy children (age, 7.80±2.19 years; boys, 55%) were included in the study. Serum concentrations of oxidized LDL, total cholesterol, triglyceride, high-density lipoprotein, LDL, and glucose were measured, and carotid IMT was determined by ultrasound. RESULTS: Serum oxidized LDL levels were significantly higher in prepubertal obese children than in healthy children (p<0.01). No significant correlation was observed between oxidized LDL levels and carotid IMT measurements. However, a significant positive correlation was found between oxidized LDL levels and body mass index, total cholesterol, and LDL-cholesterol. CONCLUSION: Our findings revealed that the oxidation of LDL starts early in obese children but the carotid IMT is not significantly affected. Also, oxidized LDL levels are more strongly associated with obesity and dyslipidemia than the carotid IMT in prepubertal children.
Asunto(s)
Aterosclerosis/diagnóstico , Grosor Intima-Media Carotídeo , Lipoproteínas LDL/sangre , Obesidad/sangre , Aterosclerosis/sangre , Aterosclerosis/patología , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: The aim of this study was to investigate the quality of life (QoL) of a group of patients with inherited metabolic diseases (IMD) who were treated with restrictive diet. METHOD: A total of 68 patients (35 boys, 51.5%; 33 girls, 48.5%) with IMD (organic acidemia [OA], n = 14; disorder of carbohydrate metabolism [CMD], n = 33; and disorder of amino acid metabolism [AMD], n = 21) and their parents were inteviewed. Both parents completed a QoL Scale for Metabolic Diseases-Parent Form, a KINDL parent questionnaire, and a depression form. All patients aged ≥4 years completed a questionnaire themselves, including the KINDL-Kid and KINDL-Kiddo self-reports. The semi-standardized interviews were carried out with patients and their parents in a clinical setting. RESULTS: The patients with bad diet compliance had lower scores for school labeling and perception of disease on both the parent and child questionnaire forms (P < 0.05). The patients were then divided into three groups (OA, CMD, AMD) for further analysis. Differences were seen between groups with regard to scores of physical function and school performance according to QoL Scale for Metabolic Diseases-Parent Form (P < 0.01). According to parent perceptions, the CMD patients had better QoL with regard to emotional wellbeing. CONCLUSION: As negative effects of the disease increased, the QoL of IMD patients and their parents decreased in terms of emotional, physical, and cognitive function. Application of expanded newborn scanning programs, early diagnosis, regular follow up, and family education would lessen the effects of the disease and improve the QoL of both families and children.
Asunto(s)
Dieta Reductora , Predisposición Genética a la Enfermedad , Enfermedades Metabólicas/psicología , Calidad de Vida , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Salud Mental , Enfermedades Metabólicas/dietoterapia , Enfermedades Metabólicas/genética , Pronóstico , Psicometría , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Patients with glycogen storage disease type I (GSD-I) often have marked hyperlipidemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy; therefore, these patients may be at high risk for the development of atherosclerosis. A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), a naturally occuring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase. ADMA causes endothelial dysfunction, vasoconstriction, blood pressure elevation, atherosclerosis, and kidney disease progression. A high prevalence of elevated plasma ADMA levels is observed in adults with hypercholesterolemia, hypertension, chronic kidney disease, diabetes mellitus, peripheral arterial disease, coronary artery disease, preeclampsia, heart failure, liver disease, stroke, and many other clinical disorders. Therefore, we aimed to evaluate the endothelial function in patients with GSD-I by using ADMA levels. High-performance liquid chromatography - based method was used for measuring ADMA and L-arginine levels in plasma. The ADMA level was similar between children with GSD-I and the age-matched healthy control group (0.9±0.28 vs. 1.1±0.45 µmol/L; p=0.18). The L-arginine plasma levels in patients with GSD-I were found to be 55.7±41.3 and 91.6±50.2 µmol/L in healthy controls. The preservation of normal endothelial function may result from diminished platelet aggregation, increased levels of apolipoprotein E, decreased susceptibility of low-density lipoprotein to oxidation (possibly related to the altered lipoprotein fatty acid profile in GSD-I), and increased antioxidative defenses in plasma protecting against lipid peroxidation.
Asunto(s)
Arginina/análogos & derivados , Arginina/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo , Peroxidación de Lípido/fisiología , Adolescente , Niño , Preescolar , Ácidos Grasos/metabolismo , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/tratamiento farmacológico , Humanos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Hipolipemiantes/uso terapéutico , MasculinoRESUMEN
Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder caused by mutations in the G6PC gene encoding glucose-6-phosphatase (G6Pase), a key enzyme for the maintenance of glucose homeostasis. Molecular analysis is a reliable and accurate way of diagnosing GSD Ia without to need for invasive liver biopsies for enzyme tests. In some ethnic groups and geographic regions, allelic homogeneity was detected in GSD Ia. In the present study, the most common 12 mutations in the world were searched by microelectronic array technology, a new method, in 27 Turkish patients diagnosed for GSD Ia and the relation between detected mutations and clinical and laboratory findings was investigated. Mutations causing the disease were detected in 45 (83.3%) of 54 alleles screened in the cases with GSD Ia. Allelic frequency of mutations (p.R83C, p.G270V, p.G188R, p.W77R) looked for were found as 68.5%, 7.4%, 3.7%, and 3.7%, respectively. p.G188R mutation was detected for the first time in a patient of Turkish origin. Eight (p.R170Q, p.Q347X, c.79delC, c.380_381insTA, p.D38V, p.W63X, c.648G>T, c.979_981delTTC) of 12 mutations looked for were coincided in none of the patients. The patient with homozygous p.W77R mutation seemed to present milder clinical and laboratory findings, compared to other patients. In conclusion, we suggest that microarray technology, which allows rapid analysis of frequently detected mutations and has considerably lower costs than other methods, can be successfully used in diagnosis of GSD Ia in populations with allelic homogeneity, such as patients of Turkish origin, instead of screening the whole gene.