RESUMEN
A boy aged 6 years and 3 months developed upper respiratory tract infection and pyrexia 2 months ago and was given oral administration of nimesulide by his parents according to directions. Half an hour later, the boy experienced convulsions and cardiopulmonary arrest, and emergency examination found hypoketotic hypoglycemia, metabolic acidosis, significant increases in serum aminotransferases and creatine kinase, and renal damage. Recovery of consciousness and vital signs was achieved after cardiopulmonary resuscitation, but severe mental and movement regression was observed. The boy had a significant reduction in free carnitine in blood and significant increases in medium- and long-chain fatty acyl carnitine, urinary glutaric acid, 3-hydroxy glutaric acid, isovalerylglycine, and ethylmalonic acid, suggesting the possibility of multiple acyl-CoA dehydrogenase deficiency. After the treatment with vitamin B2, L-carnitine, and bezafibrate, the boy gradually improved, and reexamination after 3 months showed normal biochemical parameters. The boy had compound heterozygous mutations in the ETFDH gene, i.e., a known mutation, c.341G>A (p.R114H), from his mother and a novel mutation, c.1484C>G (p.P495R), from his father. Finally, he was diagnosed with multiple acyl-CoA dehydrogenase deficiency. Reye syndrome and sudden death symptoms were caused by nimesulide-induced acute metabolic crisis. It is concluded that inherited metabolic diseases may be main causes of Reye syndrome and sudden death, and biochemical and genetic analyses are the key to identifying underlying diseases.
Asunto(s)
Niño , Humanos , Masculino , Acil-CoA Deshidrogenasa , Administración Oral , Carnitina , Muerte Súbita , Infecciones del Sistema Respiratorio , Síndrome de Reye , SulfonamidasRESUMEN
In this study, an analytical method based on ultraviolet spectroscopy was established for the rapid determination of nine components including isophorone, 4-methylene-isophorone, curcumenone, curcumenol, curdione, curzerenone, furanodienone, curcumol and germacrone in the first extraction process of Xingnaojing injection. 166 distillate samples of Gardeniae Fructus and Radix Curcumae were collected in the first extraction process of Xingnaojing injection. The ultraviolet spectra of these samples were collected, and the contents of the nine components in these samples were determined by high performance liquid chromatography. Least squares support vector machine and radial basis function artificial neural network were used to establish the multivariate calibration models between the ultraviolet spectra and the contents of the nine components. The results showed that the established ultraviolet spectrum analysis method can determine the contents of the nine components in the distillates accurately, with root mean square error of prediction of 0.068, 0.147, 0.215, 0.319, 1.01, 1.27, 0.764, 0.147, 0.610 mg•L⁻¹, respectively. This proposed method is a rapid, simple and low-cost tool for the monitoring and endpoint determination of the extraction process of Xingnaojing injection to reduce quality defects and variations.
RESUMEN
This study reports a boy with psychomotor retardation and epilepsy due to maternal phenylketonuria (PKU). The boy was admitted at the age of 20 months because of psychomotor retardation and epilepsy. He had seizures from the age of 1 year. His development quotient was 43. He presented with microcephaly, normal skin and hair color. Brain MRI scan showed mild cerebral white matter demyelination, broadening bilateral lateral ventricle and foramen magnum stricture. Chromosome karyotype, urine organic acids, blood amino acids and acylcarnitines were normal. His mother had mental retardation from her childhood. She presented with learning difficulties and yellow hair. Her premarriage health examinations were normal. She married a healthy man at age of 26 years. When she visited us at 28 years old, PKU was found by markedly elevated blood phenylalanine (916.54 μmol/L vs normal range 20-120 μmol/L). On her phenylalanine hydroxylase (PAH) gene, a homozygous mutations c.611A>G (p.Y204C) was identified, which confirmed the diagnosis of PAH-deficient PKU. Her child carries a heterozygous mutation c.611A>G with normal blood phenylalanine. Her husband had no any mutation on PAH. It is concluded that family investigation is very important for the etiological diagnosis of the children with mental retardation and epilepsy. Carefully clinical and metabolic survey should be performed for the parents with mental problems to identify parental diseases-associated child brain damage, such as maternal PKU.
Asunto(s)
Adulto , Femenino , Humanos , Lactante , Masculino , Embarazo , Epilepsia , Discapacidad Intelectual , Fenilalanina Hidroxilasa , Genética , Fenilcetonuria MaternaRESUMEN
cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene. The clinical presentations, blood acylcarnitines profiles, urine organic acids and genetic features of the patient were reported. The boy presented with fever, feeding difficulty and lethargy at the age of 2 months. Seven days later, he had coma, cold limb, thrombocytopenia, metabolic acidosis and liver damage. His blood propionylcarnitine and urinary methylmalonic acid levels increased significantly, but the plasma total homocysteine level was in the normal range, which supported the diagnosis of isolated methylmalonic aciduria. Gene analysis was performed by direct sequencing. No mutation in the MUT gene was found. However, a reported mutation c.577G>A (p.E193K) and a novel mutation c.562G>A (p.V188M) in the MMAB gene were identified, which confirmed the diagnosis of methylmalonic aciduria cblB type. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 3 years and 11 months old and has a normal development condition. The phenotypes of the patients with cblB defect are nonspecific. Metabolic analysis and MMAB gene analysis are keys for the diagnosis of the disorder.
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Humanos , Lactante , Masculino , Transferasas Alquil y Aril , Genética , Errores Innatos del Metabolismo de los Aminoácidos , Genética , MutaciónRESUMEN
Methylmalonyl CoA mutase deficiency due to MUT gene defect has been known as the main cause of isolated methylmalonic acidemia in Mainland China. This study reported a patient with isolated methylmalonic aciduria (MUT type) characterized as acute brainstem encephalitis and myelitis. The previously healthy girl presented with fever, lethargy and progressive weakness in her extremities at the age of 3 years and 2 months. Three day later, she had respiratory distress and consciousness. Cranial MRI revealed bilateral symmetrical lesion of pallidum, brain stem and spinal cord, indicating acute brainstem encephalitis and myelitis. Her blood propionylcarnitine (6.83 μmol/L vs normal range 1.0 to 5.0 μmol/L) and urinary methylmalonic acid (133.22 mmol/mol creatinine vs normal range 0.2 to 3.6 mmol/mol creatinine) increased significantly. Plasma total homocysteine was normal. On her MUT gene, a reported mutation (c.1630_1631GG>TA) and a novel mutation (c.1663C>T, p.A555T) were identified, which confirmed the diagnosis of methylmalonic aciduria (MUT type). After cobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine, progressive improvement has been observed. The clinical manifestation of patients with methylmalonic aciduria is complex. Metabolic study and gene analysis are keys for the diagnosis and treatment of the disorder.
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Preescolar , Femenino , Humanos , Enfermedad Aguda , Errores Innatos del Metabolismo de los Aminoácidos , Tronco Encefálico , Patología , Encefalitis , Metilmalonil-CoA Mutasa , Genética , Mutación , MielitisRESUMEN
Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin B12 and betaine.
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Adolescente , Humanos , Masculino , Secuencia de Bases , Homocistinuria , Diagnóstico , Quimioterapia , Metilenotetrahidrofolato Reductasa (NADPH2) , Datos de Secuencia Molecular , Espasticidad Muscular , Diagnóstico , Quimioterapia , Trastornos Psicóticos , Diagnóstico , Quimioterapia , EsquizofreniaRESUMEN
Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deficiency caused by ATP7A gene mutation. In this study, the clinical and laboratory features of three patients with Menkes disease were analyzed. Prenatal diagnosis had been performed for a fetus of a family. Three patients were admitted at the age of 8-9 months due to severe epilepsies and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging, cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2, 73.5 and 81 mg/L, significantly lower than normal range (210-530 mg/L). c.3914A>G (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation, c.3265G>T (p.G1089X) was found in case 3. Both of them were firstly found in Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G mutation on ATP7A gene was showed. Postnatal genetic analysis and normal development confirmed the prenatal diagnosis.
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Humanos , Lactante , Masculino , Adenosina Trifosfatasas , Genética , Proteínas de Transporte de Catión , Genética , ATPasas Transportadoras de Cobre , Síndrome del Pelo Ensortijado , Diagnóstico , Genética , Mutación , Diagnóstico PrenatalRESUMEN
The mammalian mitochondrial ATP synthase, also as known as mitochondrial respiratory chain complex V, is a large protein complex located in the mitochondrial inner membrane, where it catalyzes ATP synthesis from ADP, Pi, and Mg2+ at the expense of an electrochemical gradient of protons generated by the electron transport chain. Complex V is composed of 2 functional domains F0 and F1. The clinical features of patients are significantly heterogeneous depending on the involved organs. Most patients with complex V deficiency had clinical onset in the neonatal period with severe brain damage or multi-organ failure resulting in a high mortality. Neuromuscular disorders, cardiomyopathy, lactic acidosis and 3-methylglutaconic aciduria are common findings. Complex V consists of 16 subunits encoded by both mitochondrial DNA and nuclear DNA. On MT-ATP6, MT-ATP8, ATPAF2, TMEM70 and ATP5E gene of mitochondrial DNA, many mutations associated with Complex V deficiency have been identified. Here, the pathology, clinical features, diagnosis, treatment and molecular genetics of Complex V deficiency were summarized.
Asunto(s)
Enfermedades Mitocondriales , Terapéutica , ATPasas de Translocación de Protón Mitocondriales , Química , Genética , Fisiología , PronósticoRESUMEN
<p><b>OBJECTIVE</b>Mitochondrial disease is a group of energy metabolic disorders, characterized by involvement of multisystem with high energy requirements. Encephalomyopathies are common clinical findings of the mitochondrial diseases. However, mitochondrial cardiac damage is not rare. In this study, the clinical, biological, and genetic analyses were performed in three patients with mitochondrial cardiac damage, in order to understand the characteristics of mitochondrial diseases.</p><p><b>METHOD</b>Three girls presented with arrhythmia and cardiac enlargement from the age of 3, 4 and 8 years respectively. They were admitted into the Peking University First Hospital. Infection, autoimmune diseases, aminoacidopathies, organic acidurias, mitochondrial-fatty acid oxidation defects, and lysosomal storage disease were excluded by routine laboratory examinations and metabolic analysis for blood amino acids, acylcarnitines, urinary organic acids, and lysosome activity assay. Peripheral leukocytes mitochondrial respiratory chain enzyme I to V activities were measured by spectrophotometry. The entire sequence of the mitochondrial DNA was analyzed.</p><p><b>RESULT</b>In two patients (case 1 and case 3), hypertrophic cardiomyopathy and grade I to grade II of cardiac function were found. One patient (case 2) was diagnosed with arrhythmia and grade I of cardiac function. Increased creatine phosphokinase and creatine kinase isoenzyme MB were observed. Mitochondrial respiratory chain complex deficiencies were indentified in the three patients. Patient 1 had combined deficiencies of complex III and V. The activity of complex I+III was 18.7 nmol/(min·mg mitochondrial protein) (control 84.4 ± 28.5). The activity of complex V was 20.4 nmol/(min·mg mitochondrial protein) (control 103.7 ± 29.2). In her mitochondrial gene, A14693G on tRNA(Glu) and T16519C on D-loop were found. Patient 2 had an isolated complex I deficiency. The activity was 22.0 nmol/(min·mg mitochondrial protein) (control 44.0 ± 5.4). A16183C, T16189C and G15043A mutations on D-loop were found. Patient 3 had a combined deficiency of complex IV and V. The activity of complex IV was 21.0 nmol/(min·mg mitochondrial protein) (control 54.1 ± 12.3). The activity of complex V was 23.2 nmol/(min·mg mitochondrial protein) (control 103.7 ± 29.2). C253T and C16187T mutations on D-loop were detected. Haplotype analysis showed that three patients belong to H2a2a. Improvement was observed after the treatment with L-carnitine, coenzyme Q10, vitamin C and E. At present, the patients are 7, 5 and 8 years old. Although excise intolerance still persists, they had a good general condition with normal school life.</p><p><b>CONCLUSION</b>The mitochondrial diseases with cardiac damage show cardiomyopathy, arrhythmia and exercise intolerance. Many kinds of mitochondrial respiratory chain deficiency were observed. A14693G in mitochondrial tRNA(Glu) gene is probably one of the causes in China.</p>
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Niño , Preescolar , Femenino , Humanos , Masculino , Arritmias Cardíacas , Diagnóstico , Genética , Metabolismo , Biomarcadores , Sangre , Orina , Cardiomiopatía Hipertrófica , Diagnóstico , Genética , Metabolismo , Análisis Mutacional de ADN , ADN Mitocondrial , Genética , Proteínas del Complejo de Cadena de Transporte de Electrón , Genética , Metabolismo , Mitocondrias Cardíacas , Patología , Enfermedades Mitocondriales , Diagnóstico , Genética , Metabolismo , MutaciónRESUMEN
<p><b>OBJECTIVE</b>Methylmalonic aciduria is the most common disorder of organic acidurias in the mainland of China. It is also the one of treatable metabolic disorders. The clinical spectrum of the patients varies from severe neonatal-onset forms with neonatal brain injury and high mortality to milder forms with adult-onset. The clinical manifestations of neonates with methylmalonic aciduria are non-specific. Early diagnosis and adequate treatment contribute a lot to improving the prognosis of the patients. In this study, the abnormal clinical and laboratory findings in neonatal period of 160 Chinese patients with early-onset methylmalonic aciduria were investigated.</p><p><b>METHOD</b>From 1996 to 2011, a total of 398 patients with methylmalonic aciduria were diagnosed in our hospital; 286 (71.9%) patients had early-onset before 1 year of age. Among 286 patients, 160 (55.9%) presented symptoms in neonatal period. Their urine organic acids were analyzed by gas chromatography-mass spectrometry. Blood amino acids and acylcarnitine profiles were determined by liquid chromatography tandem mass spectrometry. Serum and urine total homocysteine were measured using a fluorescence polarization immunoassay. In some patients, gene analysis was performed. Based on the disease types and general condition, individual dietary and medical interventions were started soon after diagnosis.</p><p><b>RESULT</b>Out of the 160 patients, 131 (81.9%) had combined methylmalonic aciduria and homocysteinemia. Isolated methylmalonic aciduria was found in 29 cases (18.1%). The common presentations in neonatal period were feeding difficulty, seizures, lethargy and dyspnea. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent findings in the routine laboratory test. The most common initial clinical diagnosis was suspected hypoxic-ischemic encephalopathy. Even in 36 cases with abnormal family history, only 3 patients were admitted with suspected inborn errors of metabolism. Five cases (3.1%) were diagnosed by postmortem metabolic examination; 7 cases (4.4%) were detected by newborn screening. In 148 cases (92.5%), the diagnosis was much delayed to the age of one month to 8 years and 5 months (mean 13 months). Methylmalonic aciduria combined with homocysteinemia (MMACHC) gene analyses were performed in 31 cases with combined methylmalonic aciduria. CblC defect was confirmed. The patients with isolated methylmalonic aciduria were treated with protein-restricted diet, cobalamin and L-carnitine. The patients of methylmalonic aciduria combined with homocysteinemia were treated with cobalamin, L-carnitine, calcium folinate, betaine and common diet. Seven patients died without treatment. Clinical improvement was observed in 153 patients. Only 2 patients detected by newborn screening had normal mental and physical development. Mild to severe psychomotor retardation was observed in 151 cases.</p><p><b>CONCLUSION</b>High mortality and disability rates were observed in the patients with early-onset methylmalonic aciduria. Combined methylmalonic aciduria and homocysteinemia is the common type of methylmalonic aciduria. The clinical manifestation in neonatal period of the patients with early-onset methylmalonic aciduria is complex. Feeding difficulty, seizures, lethargy and dyspnea are the common symptoms in neonatal period of the patients. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent laboratory findings.</p>
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Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Errores Innatos del Metabolismo de los Aminoácidos , Diagnóstico , Genética , Terapéutica , Carnitina , Usos Terapéuticos , China , Epidemiología , Ácido Fólico , Usos Terapéuticos , Cromatografía de Gases y Espectrometría de Masas , Homocisteína , Sangre , Orina , Hiperhomocisteinemia , Diagnóstico , Terapéutica , Ácido Metilmalónico , Orina , Tamizaje Neonatal , Estudios Retrospectivos , Vitamina B 12 , Usos TerapéuticosRESUMEN
Mitochondrial respiratory chain deficiency is a common cause of mitochondrial disease in children. This study aimed to review the clinical, enzymatic and genetic characteristics of a Chinese boy with progressive intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency. The boy developed diarrhea from the age of 13 months, followed by progressive body weight loss, jaundice and weakness. His urine organic acids, blood amino acids and acylcarnitines profiles were normal. Mitochondrial respiratory chain complexes I to V activities in peripheral leukocytes were measured using spectrophotometric assay. Complex I activity was reduced. 5821G>A mutation was indentified by gene sequencing on tRNA-cys of mitochondrial gene in the patient and his mother. Vitamin supplements, liver protection, antibiotics and plasma infusion were not effective in the patient. Unfortunately, the boy died at the age of 17 months. Mitochondrial respiratory chain complex I deficiency is the most common mitochondrial respiratory chain disorder. This was the first case of intrahepatic cholestasis due to complex I deficiency confirmed by mitochondrial respiratory chain enzyme activity assay and gene analysis in China. It was concluded that mitochondrial hepatopathy is one of major causes of metabolic hepatopathy. Biochemical assay, mitochondrial respiratory chain complex activities assay and genetic analysis are crucial for the etiological diagnosis of metabolic hepatopathy.
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Humanos , Lactante , Masculino , Colestasis Intrahepática , Diagnóstico , Diagnóstico Diferencial , Complejo I de Transporte de Electrón , Enfermedades MitocondrialesRESUMEN
<p><b>OBJECTIVE</b>To investigate drug treatment of inpatients with chronic heart failure(CHF) during the past 30 years in some areas and to provide more information on the treatment strategy of CHF.</p><p><b>METHODS</b>In two centers a retrospective study was conducted. All data were taken from the hospitalized cases with chronic heart failure. The medication distributions in different decade, gender, age heart function grade and etiology were analyzed.</p><p><b>RESULTS</b>5189 cases were enrolled with the ratio of male to female as 1:1.02. The mean age was (62.93 +/- 13.49) years old. The general causes of chronic heart failure were as follows: coronary heart disease (44.2%), rheumatic heart disease (24.1% ) , pulmonary heart disease (19.0%) and cardiomyopathy (4.8%). The admission cardiac function was mostly seen as grade NYHA IlI and IV, and their proportions were 40.6% and 44.5%. Major medication would include nitride (80.0%), diuretics (71.8% ), digitalis (68.1% ), angiotensin conversion enzyme inhibitors (ACEI) (52.2% ) and beta-blockers (19.5% ) etc. Moreover the frequency of above used medication was essentially increasing decade by decade. The major drug treatment of pulmonary heart disease also included diuretics, nitride, digitalis. ACEI was more commonly used in male than in female cases. The frequency of ACEI and ARB were more commonly used in the group > or = 60 years old than that in the group < 60 years old. The administration frequency of beta- blockers had no significant difference among different age and sexes.</p><p><b>CONCLUSION</b>The conventional drugs such as nitride, diuretics, digitalis were still dominated the treatment of CHF. Although the administration frequency of ACEI and beta-blockers increased quickly, there had been a great gap between the optimal medical strategy and clinical practice in the management of CHF. Data showed the treatment strategy was changing.</p>
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Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Adrenérgicos beta , Usos Terapéuticos , Inhibidores de la Enzima Convertidora de Angiotensina , Usos Terapéuticos , Enfermedad Crónica , Diuréticos , Usos Terapéuticos , Insuficiencia Cardíaca , Quimioterapia , Hospitalización , Estudios RetrospectivosRESUMEN
OBJECTIVE@#To explore the objective evidence of the corpus biochemical changes in rabbits for postmortem diagnosis of potassium intoxication.@*METHODS@#Rabbits were sacrificed by Infusion of 0.3% KCl at full speed push or 1% KCl at 100 drip/min, respectively, with normal rabbits used as control. Cardiac blood and urine samples were collected before and after potassium infusion to examine the concentrations of various electrolytes (K+, Na+, Ca2+, Mg2+, Cl-, and HCO3-) and to observe the antemortem and postmortem biochemical changes.@*RESULTS@#The mean lethal infusion time in the 0.3%KCl group was longer than that in the 1% KCl group (P = 0.006). The serum concentration of K+ increased while the serum concentrations of Na+, Ca2+, Cl-, and HCO3- decreased after the infusion. There were no statistically significant differences in the whole blood concentration of K+ as well as the serum concentration of Mg2+ between the two groups (P = 0.062). There were statistically significant differences in the concentrations of whole blood K+, as well as serum Na+, Mg2+, and Cl-, but not in the serum K+, Ca2+, and HCO3-. There were no statistically significant differences seen in the urine volumes and the concentrations of all the urine electrolytes between the groups.@*CONCLUSION@#Examination of the concentrations of K+ both in the whole blood and serum, as well as Mg2+ in the serum may be helpful for postmortem diagnosis of potassium intoxication.