Journal of Inborn Errors of Metabolism and Screening最新文献_第6页

A Case Report on the Challenging Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 2型神经性脑蜡样脂褐质病(CLN2)诊断困难1例报告

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2020-01-01 DOI: 10.1590/2326-4594-jiems-2020-0010

A. Nunes, J. Meira, C. Cunha, M. Veiga, Ana Paula Pereira Scholz de Magalhães, D. R. Málaga, R. Giugliani, E. Leão

{"title":"A Case Report on the Challenging Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)","authors":"A. Nunes, J. Meira, C. Cunha, M. Veiga, Ana Paula Pereira Scholz de Magalhães, D. R. Málaga, R. Giugliani, E. Leão","doi":"10.1590/2326-4594-jiems-2020-0010","DOIUrl":"https://doi.org/10.1590/2326-4594-jiems-2020-0010","url":null,"abstract":" Abstract Neuronal ceroid lipofuscinoses (NCLs), also referred as “Batten disease”, are a group of thirteen rare genetic conditions, which are part of the lysosomal storage disorders. CLN type 2 (CLN2) is caused by the deficient activity of the tripeptidyl peptidase I (TPP1) enzyme, encoded by the TPP1 gene, most frequently leading to the classic late infantile phenotype. Nearly 140 CLN2-causing mutations have been described. In this case report, we describe the identification of a new disease-causing mutation and highlight the importance of appropriate laboratory investigation based on clinical suspicion. The collection of dried blood spots (DBS) on filter paper, which is a convenient sample, can be used to measure the TPP1 enzyme activity and detect CLN2-related mutations. Since the biochemical and genetic diagnoses are possible and as the disease progression is fast and the therapeutic window is short, the investigation of CLN2 should be always considered when this diagnostic hypothesis is raised in order to enable the patients to benefit from the specific pharmacological","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89862240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Genotype-Phenotype Variations of Renal Complications in Fabry Disease Q279X Mutation 法布里病Q279X突变肾并发症的基因型-表型变异

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2020-01-01 DOI: 10.1590/2326-4594-jiems-2020-0007

J. Villalobos, Carmen C García, J. Politei, J. Frabasil, V. L. Colina

{"title":"Genotype-Phenotype Variations of Renal Complications in Fabry Disease Q279X Mutation","authors":"J. Villalobos, Carmen C García, J. Politei, J. Frabasil, V. L. Colina","doi":"10.1590/2326-4594-jiems-2020-0007","DOIUrl":"https://doi.org/10.1590/2326-4594-jiems-2020-0007","url":null,"abstract":"In more than 800 GLA gene mutations causing Fabry Disease (FD), renal involvement vary according to the α-GAL A mutation. The aim is to describe the genotype/phenotype variations of renal complications in two siblings with confirmed FD with the mutation p.Q279X in exon 6. We present a retrospective study of two venezuelan male siblings, ages 34 (patient 1) and 33 (patient 2), evaluated by general lab tests, renal ultrasound, renal scintigram , and renal biopsy. Fabry disease diagnose was made by α-galactosidase A activity determined in dried blood spot. Genomic DNA was sequenced by Sanger method. Patient 1 developed CKD grade 5 and high blood pressure, treated by hemodialysis during 8 years. Patient 2 showed GFR >60 ml/min, and proteinuria less than 600 mg/24H. Renal biopsy showed segmental sclerotic lesions and hypertrophic podocytes with vacuolated cytoplasm. Both patients received ERT every two weeks since 2003. Patient 1 died because dialysis complications (hyperparathyroidism, cardiomyopathy). The genotype/phenotype variation of the c.835C>T mutation (p.Gln279Ter. Q279X) in exon 6 of the GLA gene can express an important renal variation with a wide range of clinical manifestations that cannot be predicted, therefore, an early nephrological evaluation and periodic follow-up of these patients are necessary.","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73896304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Application of Liquid Chromatography Tandem Mass Spectrometry Using Dried Blood Spot as a More Rapid Method for Determination of Methylmalonic Acid, Propionylcarnitine, and Total Homocysteine 干血斑液相色谱串联质谱法快速测定甲基丙二酸、丙酰肉碱和总同型半胱氨酸的临床应用

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2020-01-01 DOI: 10.1590/2326-4594-jiems-2019-0005

Hiroyuki Iijima, Nobuyuki Ishige, M. Kubota

{"title":"Clinical Application of Liquid Chromatography Tandem Mass Spectrometry Using Dried Blood Spot as a More Rapid Method for Determination of Methylmalonic Acid, Propionylcarnitine, and Total Homocysteine","authors":"Hiroyuki Iijima, Nobuyuki Ishige, M. Kubota","doi":"10.1590/2326-4594-jiems-2019-0005","DOIUrl":"https://doi.org/10.1590/2326-4594-jiems-2019-0005","url":null,"abstract":"Methylmalonic acidemia (MMA) should be diagnosed in early infancy and receive appropriate management promptly after the diagnosis to prevent severe complications leading to death. At present, a newborn screening (NBS) method using tandem mass spectrometry (MS/MS) identifies suspected patients with MMA by elevated propionylcarnitine. In addition, a liquid chromatography tandem mass spectrometry (LC/MS/MS) method using dried blood spot is effective to detect some metabolites as a second-tier test, and reduces the false-positive rate in NBS. However, these tests were only used in screening, and not applied as an examination for evaluating treatment. Herein, we describe a 57-day-old girl with MMA under treatment with cobalamin who had elevated urinary methylmalonic acid levels. We applied the LC/MS/MS method with a separation column to evaluate her cobalamin responsiveness, and discovered an insufficient cobalamin dose earlier than would have been possible using other methods. Based on the current data, this method seems to be applicable for the follow-up of the treatment of MMA patients. However, this should be confirmed with more experience with a larger number of cases and a wider spectrum of disorders.","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"212 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79430602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The Challenges of Living with and Caring for a Child or Children Affected by Neuronal Ceroid Lipofuscinosis Type 2 Disease: In-Depth Family Surveys in the United Kingdom and Germany 与患有神经性神经样脂褐膜病2型的儿童一起生活和照顾的挑战:英国和德国的深入家庭调查

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2020-01-01 DOI: 10.1590/2326-4594-jiems-2019-0013

A. Schulz, Mohit J. Jain, T. Butt, R. Ballinger, L. Eliasson, J. Macey, T. Peasgood, A. Olaye, Irini-Alexia Terzakis-Snyder, I. Dyck, Andrea West

{"title":"The Challenges of Living with and Caring for a Child or Children Affected by Neuronal Ceroid Lipofuscinosis Type 2 Disease: In-Depth Family Surveys in the United Kingdom and Germany","authors":"A. Schulz, Mohit J. Jain, T. Butt, R. Ballinger, L. Eliasson, J. Macey, T. Peasgood, A. Olaye, Irini-Alexia Terzakis-Snyder, I. Dyck, Andrea West","doi":"10.1590/2326-4594-jiems-2019-0013","DOIUrl":"https://doi.org/10.1590/2326-4594-jiems-2019-0013","url":null,"abstract":"Limited research has investigated the challenges faced by families caring for children with neuronal ceroid lipofuscinosis type 2 (CLN2) disease. Face-to-face, mixed-method, in-depth surveys were conducted with 19 families (23 children) in the UK (n=9) and Germany (n=10) to assess the impact of caring for children with CLN2 disease, using national wellbeing and quality of life (QoL) measures. Primary (n=19) and secondary (n=10) caregivers, adult siblings (n=2), and child siblings (n=2) were included. Caregivers reported reduced health-related QoL compared with age and gender-matched controls (mean utility scores 0.08 and 0.11 lower in Germany and the UK, respectively). Hours of caregiving were significantly higher relative to that provided to a child of normal health, with stress, back pain, and reductions in sleep being recorded. Lower life satisfaction and happiness with partners were also reported, along with significant financial burden. Those caring for children in the late stage of disease were more greatly impacted than those with children in the rapidly progressive stage, or who were bereaved. The results of this study make clear the importance of emotional and practical support for caregivers and siblings coping with CLN2 disease.","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81983049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Otorhinolaryngological Findings in Patients from Southwestern Colombia with Clinical, Enzymatic and Molecular Diagnosis of Mucopolysaccharidosis II, IV-A and VI 哥伦比亚西南部粘多糖病II型、iv型、a型和VI型临床、酶学和分子诊断患者的耳鼻喉科表现

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2020-01-01 DOI: 10.1590/2326-4594-jiems-2019-0006

L. Giraldo, D. Arturo-Terranova, J. M. Soto

引用次数: 4

Neonatal Screening for Congenital Hypothyroidism in Nicaragua: Audit of a Cord-blood Thyrotropin-based Program (2005-2015) 尼加拉瓜新生儿先天性甲状腺功能减退筛查:2005-2015年脐带血促甲状腺素项目审计

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2019-01-01 DOI: 10.1590/2326-4594-jiems-2019-0003

A. Funez, M. E. Lara, A. Chévez, E. Castellón, S. Perán, M. J. Toro, Eladio Montoya, J. Varró

{"title":"Neonatal Screening for Congenital Hypothyroidism in Nicaragua: Audit of a Cord-blood Thyrotropin-based Program (2005-2015)","authors":"A. Funez, M. E. Lara, A. Chévez, E. Castellón, S. Perán, M. J. Toro, Eladio Montoya, J. Varró","doi":"10.1590/2326-4594-jiems-2019-0003","DOIUrl":"https://doi.org/10.1590/2326-4594-jiems-2019-0003","url":null,"abstract":" Abstract The aim of this study is to evaluate the Nicaraguan screening program for congenital hypothyroidism in terms of coverage and effectiveness of detection and confirmation of cases with the condition throughout a decade. Thyrotropin was quantified in cord-blood samples by a validated ELISA and a cut-off of 20 mU/l was applied. Coverage, positive predictive value, recall rate and prevalence were retrospectively analysed. Babies with positive screening results were contacted for confirmation by means of determination of thyrotropin and thyroid profile in serum samples. 272,338 babies were screened during the period 2005-2015. The mean coverage reached by the program in the participating departments was 71%, with a positive predictive value of 83% and a recall rate of 0.055%. Eighty cases of congenital hypothyroidism were identified, representing an incidence of 1 in 3229 live births, most of them (81%) being severe. The performance of the Nicaraguan screening program is comparable to those in Latin America also using cord-blood samples. The incidence of congenital hypothyroidism is within the low range of other countries worldwide. Strategies are needed to expand the program to the whole country, improve recall rates and achieve earlier treatment of babies, with the","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85803641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Recommendations for Assessment and Management of Health-Related Quality of Life in Patients with Mucopolysaccharidoses in Latin America 拉丁美洲黏多糖病患者健康相关生活质量评估和管理建议

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2019-01-01 DOI: 10.1590/2326-4594-JIEMS-2019-0004

R. Giugliani, A. Fainboim, C. Kim, D. Horovitz, E. T. Sakata, A. Damiano, T. Magalhães, Martha L. Solano Villareal

{"title":"Recommendations for Assessment and Management of Health-Related Quality of Life in Patients with Mucopolysaccharidoses in Latin America","authors":"R. Giugliani, A. Fainboim, C. Kim, D. Horovitz, E. T. Sakata, A. Damiano, T. Magalhães, Martha L. Solano Villareal","doi":"10.1590/2326-4594-JIEMS-2019-0004","DOIUrl":"https://doi.org/10.1590/2326-4594-JIEMS-2019-0004","url":null,"abstract":"Mucopolysaccharidoses (MPS) constitute a heterogeneous group of rare genetic disorders caused by enzymatic deficiencies that lead to the accumulation of glycosaminoglycans (GAGs). Clinical observations suggest a health-related impairment in quality of life in patients with MPS. Professionals with extensive experience in the care of patients with inborn errors of metabolism, such as MPS, held a meeting in April 2017 to discuss and propose recommendations for the evaluation and management of quality of life in MPS patients in Latin America. In the light of this scenario, the present work summarizes the content of the discussions and presents the recommendations produced at the meeting. The panel had suggested the use of the following tools for the assessment of health-related quality of life (HRQoL): Children’s Health Assessment Questionnaire (CHAQ) for children and patients unable to express their feelings, Health Assessments Questionnaire (HAQ) and EuroQol 5 Domains (EQ-5D) scales for adult patients. Based on the scores verified in these scales, the panel proposes interventions that aim reducing the impairment of the quality of life in patients with MPS disorders.","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86867080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Isolated Sulfite Oxidase Deficiency: Response to Dietary Treatment in a Patient with Severe Neonatal Presentation 孤立亚硫酸盐氧化酶缺乏症:对新生儿重症患者饮食治疗的反应

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2019-01-01 DOI: 10.1590/2326-4594-JIEMS-2019-0001

M. Boyer, M. Sowa, Raymond Y. Wang, J. Abdenur

{"title":"Isolated Sulfite Oxidase Deficiency: Response to Dietary Treatment in a Patient with Severe Neonatal Presentation","authors":"M. Boyer, M. Sowa, Raymond Y. Wang, J. Abdenur","doi":"10.1590/2326-4594-JIEMS-2019-0001","DOIUrl":"https://doi.org/10.1590/2326-4594-JIEMS-2019-0001","url":null,"abstract":" Abstract Isolated sulfite oxidase deficiency (ISOD) is a devastating, neurometabolic disorder caused by mutations in the SUOX gene necessary for the final step in the sulfur-containing amino acid catabolic pathway. Patients classically present in the neonatal period with neurologic manifestations. Biochemical findings include elevated sulfocysteine, low cystine and undetectable homocysteine with normal uric acid levels. Other associated biochemical markers include elevated plasma alpha-aminoadipic semialdehyde and piperideine-6-carboxylic acid. We report a patient with classic neonatal onset ISOD (refractory seizures, hypertonicity, brain abnormalities, pathogenic SUOX mutations). Her clinical course was marked by extreme irritability, prompting the use of a low methionine and cystine diet to decrease toxic metabolites thought to be contributing to her symptoms. Biochemical markers and extreme irritability improved with dietary treatment (methionine=30mg/kg/day). She died of sepsis in early infancy, precluding long term follow-up. This case reviews the potential benefits and limitations of diet therapy in this rare","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76704154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Home-Based Care for Patients with Lysosomal Storage Disease: Experiences in Argentina 溶酶体贮积症患者的家庭护理:阿根廷的经验

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2019-01-01 DOI: 10.1590/2326-4594-JIEMS-2018-0002

M. Brunelli, M. M. Rabhansl, Clara Delacre, M. Dankert, Maria Victoria Cuevillas, Catalina Terán Frias

引用次数: 3

Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients 阿根廷PKU患者苯丙氨酸羟化酶(PAH)基因分型

Journal of Inborn Errors of Metabolism and Screening Pub Date : 2019-01-01 DOI: 10.1590/2326-4594-jiems-2019-0012

Rosa Enacan, M. N. Miñana, L. Fernández, M. Valle, M. Salerno, Claudia I. Fraga, F. Santos-Simarro, L. Prieto, P. Lapunzina, N. Specola, A. Chiesa

{"title":"Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients","authors":"Rosa Enacan, M. N. Miñana, L. Fernández, M. Valle, M. Salerno, Claudia I. Fraga, F. Santos-Simarro, L. Prieto, P. Lapunzina, N. Specola, A. Chiesa","doi":"10.1590/2326-4594-jiems-2019-0012","DOIUrl":"https://doi.org/10.1590/2326-4594-jiems-2019-0012","url":null,"abstract":"Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg ́s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.","PeriodicalId":56346,"journal":{"name":"Journal of Inborn Errors of Metabolism and Screening","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75342104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8