Cystic duct cysts are rare lesions, and type VI of TODANI’s modified classification is the rarest subtype with only sporadic case reports in the literature. The following report describes the coexistence of this enti...Cystic duct cysts are rare lesions, and type VI of TODANI’s modified classification is the rarest subtype with only sporadic case reports in the literature. The following report describes the coexistence of this entity and type 1 tyrosinemia in a one month-old infant referred to our department for etiological investigations of prolonged neonatal cholestasis. To the best of our knowledge, we report herein the first case in the literature describing this association. Cystic duct abnormalities should be considered in the differential diagnosis of neonatal cholestases, however further investigations should be performed to exclude associated life-threatening conditions such as metabolic disorders including tyrosinemia.展开更多
Objective. Between October and November 2003,several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that ...Objective. Between October and November 2003,several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1),specifically manufactured for the Israeli market. The source was identified on November 6,2003,when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus,ophthalmoplegia,and vomiting. Wernicke’s encephalopathy was suspected,and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula,raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities,and the thiamine level was found to be undetectable (< 0.5 μ g/g). The product was pulled from the shelves,and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis,clinical course,and outcome of 9 affected infants in our care. Methods. After the index case,an additional 8 infants were identified in our centers by medical history,physical examination,and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay,where in the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15% ; a value of 15% to 25% indicates thiamine deficiency,and > 25% indicates severe deficiency. Blood lactate levels (normal:0.5-2 mmol/L) were measured in 6 infants,cerebrospinal fluid lactate in 2 (normal:0.5-2 mmol/L),and blood pyruvate in 4 (normal:0.03-0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula. Results. Early symptoms were nonspecific and includedmainly vomiting (n=8),lethargy (n=7),irritability (n =5),abdominal distension (n=4),diarrhea (n=4),respiratory symptoms (n=4),developmental delay (n= 3),and failure to thrive (n=2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection:acute gastroenteritis (n=2); upper respiratory infection (n=2); and bronchopneumonia,a cute bronchitis,and viral infection (n=1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis,and 2 had high cerebrospinal fluid lactate levels. Patient 1,our index case,was hospitalized for upbeat nystagmus and ophthalmoplegia,in addition to daily vomiting episodes since 4 months of age and weight loss of 0.5 kg. Findings on brain computed tomography were normal. Blood lactate levels were high,and TPPE was 37.8% . Brain magnetic resonance imaging (MRI) revealed no abnormalities. Patient 2,who presented at 5 months with lethargy,vomiting,grunting,and abdominal tenderness,was found to have intussusception on abdominal ultrasound and underwent 2 attempts at reduction with air enema several hours apart. However,the lethargy failed to resolve and ophthalmoplegia appeared the next day,leading to suspicions of Wernicke’s encephalopathy. Laboratory tests showed severe thiamine deficiency (TPPE 31.2% ). In patients 1 and 2,treatment led to complete resolution of symptoms. The third infant,a 5-month-old girl,was admitted on October 10,2003,well before the outbreak was recognized,with vomiting,fever,and ophthalmoplegia. Her condition deteriorated to seizures,apnea,and coma. Brain MRI showed a bilateral symmetrical hyperintense signal in the basal ganglia,mamillary bodies,and periaqueductal gray matter. Suspecting a metabolic disease,vitamins were added to the intravenous solution,including thiamine 250 mg twice a day. Clinical improvement was noted 1 day later. TPPE assay performed after treatment with thiamine was started was still abnormal (17.6% ). Her formula was substituted after 4 weeks,after the announcement about the thiamine deficiency. Although the MRI findings improved 5 weeks later,the infant had sequelae of ophthalmoplegia and motor abnormalities and is currently receiving physiotherapy. All 3 patients with neurologic manifestations were fed exclusively with the soy-based formula for 2 to 3.5 months,whereas the others had received solid food supplements. Longer administration of the formula (ie,chronic thiamine deficiency) was associated with failure to thrive. For example,one 12-month-old girl who received the defective formula for 8 months presented with refusal to eat,vomiting,failure to thrive (75th to < 5th percentile),hypotonia,weakness,and motor delay. Extensive workup was negative for malabsorption and immunodeficiency. On admission,the patient had Salmonella gastroenteritis and sepsis and was treated with antibiotics. After thiamine deficiency was diagnosed,she received large doses of thiamine (50 mg/day) for 2 weeks. Like the other 5 infants without neurologic involvement,her clinical signs and symptoms disappeared completely within 2 to 3 weeks of treatment,and TPPE levels normalized within 1 to 7 days. There were no side effects. As part of its investigation,the Israel Ministry of Health screened 156 infants who were fed the soy-based formula for thiamine deficiency. However,by that time,most were already being fed alternative formulas and had begun oral thiamine treatment. Abnormal TPPE results (> 15% ) were noted in 8 infants,3 male and 5 female,all > 1 year old,who were receiving solid food supplements. Although their parents failed to notice any symptoms,irritability,lethargy,vomiting,anorexia,failure to thrive,and developmental delay were documented by the examining physicians. None had signs of neurologic involvement. Treatment consisted of oral thiamine supplements for 2 weeks. Conclusions. Clinician awareness of the possibility of thiamine deficiency even in well-nourished infants is important for early recognition and prevention of irreversible brain damage. Therapy with large doses of thiamine should be initiated at the earliest suspicion of vitamin depletion,even before laboratory evidence is available and before neurologic or cardiologic symptoms appear.展开更多
Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement ...Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement therapy (ERT), with recombinant human GAA for the early onset PD patient, a relevant field of clinical research due to the benefits regarding survival rate has been widely documented worldwide. Objective: To describe the clinical characteristics and the ERT effects in a series of Brazilian patients with infantile onset PD (IOPD) under ERT. Methods: Brazilian patients diagnosed with IOPD under ERT were recruited through their physicians participating in the International Pompe Disease Registry from 2009 to 2017. Data were collected by an online survey. Results: 10 IOPD patients were identified through the survey with a death rate of 30% and technology dependency rate reported as 80% (motor, respiratory or nutritional fields) of the patients. After the third year of ERT, motor disabilities were lost in 50% of ambulated patients. The overall characteristics were similar to international studies. Conclusion: Despite ERT benefits in cardiac involvement, motor disabilities seem to be much more compromised in IOPD patients, with high technology dependence, especially after three years of age.展开更多
Crowdfunding refers to the online gathering of finance via numerous small donations from individual supporters （the ＂crowd＂） in order to fund a service, project or cause from various fields including business, art...Crowdfunding refers to the online gathering of finance via numerous small donations from individual supporters （the ＂crowd＂） in order to fund a service, project or cause from various fields including business, arts, medicine and science （Sisler, 2012; Cameron et al., 2013; Weigmann, 2013; Wheat et al., 2013）. Crowdfunding platforms facilitate the interaction between organizations soliciting funding for their projects and the people who wish to support them. As prices of molecular testing plummet, utilizing crowdfunding in order to support genetic research becomes increasingly feasible （Cameron et al., 2013）. Whole Exome Sequencing （WES） has been used extensively for the purpose of identifying the genetic cause of rare mendelian diseases, uncovering novel mutations in previously implicated genes or identifying new disease- causing genes （Ng et al., 2009; Bamshad et al., 2011; Gilissen et al., 2011）.展开更多
文摘Cystic duct cysts are rare lesions, and type VI of TODANI’s modified classification is the rarest subtype with only sporadic case reports in the literature. The following report describes the coexistence of this entity and type 1 tyrosinemia in a one month-old infant referred to our department for etiological investigations of prolonged neonatal cholestasis. To the best of our knowledge, we report herein the first case in the literature describing this association. Cystic duct abnormalities should be considered in the differential diagnosis of neonatal cholestases, however further investigations should be performed to exclude associated life-threatening conditions such as metabolic disorders including tyrosinemia.
文摘Objective. Between October and November 2003,several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1),specifically manufactured for the Israeli market. The source was identified on November 6,2003,when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus,ophthalmoplegia,and vomiting. Wernicke’s encephalopathy was suspected,and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula,raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities,and the thiamine level was found to be undetectable (< 0.5 μ g/g). The product was pulled from the shelves,and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis,clinical course,and outcome of 9 affected infants in our care. Methods. After the index case,an additional 8 infants were identified in our centers by medical history,physical examination,and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay,where in the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15% ; a value of 15% to 25% indicates thiamine deficiency,and > 25% indicates severe deficiency. Blood lactate levels (normal:0.5-2 mmol/L) were measured in 6 infants,cerebrospinal fluid lactate in 2 (normal:0.5-2 mmol/L),and blood pyruvate in 4 (normal:0.03-0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula. Results. Early symptoms were nonspecific and includedmainly vomiting (n=8),lethargy (n=7),irritability (n =5),abdominal distension (n=4),diarrhea (n=4),respiratory symptoms (n=4),developmental delay (n= 3),and failure to thrive (n=2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection:acute gastroenteritis (n=2); upper respiratory infection (n=2); and bronchopneumonia,a cute bronchitis,and viral infection (n=1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis,and 2 had high cerebrospinal fluid lactate levels. Patient 1,our index case,was hospitalized for upbeat nystagmus and ophthalmoplegia,in addition to daily vomiting episodes since 4 months of age and weight loss of 0.5 kg. Findings on brain computed tomography were normal. Blood lactate levels were high,and TPPE was 37.8% . Brain magnetic resonance imaging (MRI) revealed no abnormalities. Patient 2,who presented at 5 months with lethargy,vomiting,grunting,and abdominal tenderness,was found to have intussusception on abdominal ultrasound and underwent 2 attempts at reduction with air enema several hours apart. However,the lethargy failed to resolve and ophthalmoplegia appeared the next day,leading to suspicions of Wernicke’s encephalopathy. Laboratory tests showed severe thiamine deficiency (TPPE 31.2% ). In patients 1 and 2,treatment led to complete resolution of symptoms. The third infant,a 5-month-old girl,was admitted on October 10,2003,well before the outbreak was recognized,with vomiting,fever,and ophthalmoplegia. Her condition deteriorated to seizures,apnea,and coma. Brain MRI showed a bilateral symmetrical hyperintense signal in the basal ganglia,mamillary bodies,and periaqueductal gray matter. Suspecting a metabolic disease,vitamins were added to the intravenous solution,including thiamine 250 mg twice a day. Clinical improvement was noted 1 day later. TPPE assay performed after treatment with thiamine was started was still abnormal (17.6% ). Her formula was substituted after 4 weeks,after the announcement about the thiamine deficiency. Although the MRI findings improved 5 weeks later,the infant had sequelae of ophthalmoplegia and motor abnormalities and is currently receiving physiotherapy. All 3 patients with neurologic manifestations were fed exclusively with the soy-based formula for 2 to 3.5 months,whereas the others had received solid food supplements. Longer administration of the formula (ie,chronic thiamine deficiency) was associated with failure to thrive. For example,one 12-month-old girl who received the defective formula for 8 months presented with refusal to eat,vomiting,failure to thrive (75th to < 5th percentile),hypotonia,weakness,and motor delay. Extensive workup was negative for malabsorption and immunodeficiency. On admission,the patient had Salmonella gastroenteritis and sepsis and was treated with antibiotics. After thiamine deficiency was diagnosed,she received large doses of thiamine (50 mg/day) for 2 weeks. Like the other 5 infants without neurologic involvement,her clinical signs and symptoms disappeared completely within 2 to 3 weeks of treatment,and TPPE levels normalized within 1 to 7 days. There were no side effects. As part of its investigation,the Israel Ministry of Health screened 156 infants who were fed the soy-based formula for thiamine deficiency. However,by that time,most were already being fed alternative formulas and had begun oral thiamine treatment. Abnormal TPPE results (> 15% ) were noted in 8 infants,3 male and 5 female,all > 1 year old,who were receiving solid food supplements. Although their parents failed to notice any symptoms,irritability,lethargy,vomiting,anorexia,failure to thrive,and developmental delay were documented by the examining physicians. None had signs of neurologic involvement. Treatment consisted of oral thiamine supplements for 2 weeks. Conclusions. Clinician awareness of the possibility of thiamine deficiency even in well-nourished infants is important for early recognition and prevention of irreversible brain damage. Therapy with large doses of thiamine should be initiated at the earliest suspicion of vitamin depletion,even before laboratory evidence is available and before neurologic or cardiologic symptoms appear.
文摘Pompe disease (PD) is a rare inborn error of metabolism due to an abnormal acid alpha-glucosidase (GAA) activity that comprises glycogen breakdown mainly in the lysosomes. Since the introduction of enzyme replacement therapy (ERT), with recombinant human GAA for the early onset PD patient, a relevant field of clinical research due to the benefits regarding survival rate has been widely documented worldwide. Objective: To describe the clinical characteristics and the ERT effects in a series of Brazilian patients with infantile onset PD (IOPD) under ERT. Methods: Brazilian patients diagnosed with IOPD under ERT were recruited through their physicians participating in the International Pompe Disease Registry from 2009 to 2017. Data were collected by an online survey. Results: 10 IOPD patients were identified through the survey with a death rate of 30% and technology dependency rate reported as 80% (motor, respiratory or nutritional fields) of the patients. After the third year of ERT, motor disabilities were lost in 50% of ambulated patients. The overall characteristics were similar to international studies. Conclusion: Despite ERT benefits in cardiac involvement, motor disabilities seem to be much more compromised in IOPD patients, with high technology dependence, especially after three years of age.
基金supported in part by a fellowship from the Edmond J.Safra Center for Bioinformatics at Tel-Aviv University
文摘Crowdfunding refers to the online gathering of finance via numerous small donations from individual supporters （the ＂crowd＂） in order to fund a service, project or cause from various fields including business, arts, medicine and science （Sisler, 2012; Cameron et al., 2013; Weigmann, 2013; Wheat et al., 2013）. Crowdfunding platforms facilitate the interaction between organizations soliciting funding for their projects and the people who wish to support them. As prices of molecular testing plummet, utilizing crowdfunding in order to support genetic research becomes increasingly feasible （Cameron et al., 2013）. Whole Exome Sequencing （WES） has been used extensively for the purpose of identifying the genetic cause of rare mendelian diseases, uncovering novel mutations in previously implicated genes or identifying new disease- causing genes （Ng et al., 2009; Bamshad et al., 2011; Gilissen et al., 2011）.
