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1.
BMC Immunol ; 20(1): 15, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117958

RESUMO

BACKGROUND: Mannose-binding lectin (MBL) deficiency may increase risk of respiratory tract infection in adults unselected for IgG or IgG subclass levels. In a retrospective study, we sought to determine associations of serum MBL levels with clinical and laboratory characteristics of unrelated non-Hispanic white adults at diagnosis of IgG subclass deficiency (IgGSD). We computed the correlation of first and second MBL levels expressed as natural logarithms (ln) in a patient subgroup. We compared these characteristics of all adults with and without MBL ≤50 ng/mL: age; sex; body mass index; upper/lower respiratory tract infection; diabetes; autoimmune condition(s); atopy; other allergy; corticosteroid therapy; and subnormal serum IgG subclasses, IgA, and IgM. We performed logistic regression on MBL ≤50 ng/mL (dichotomous) using the three independent variables with the lowest values of p in univariate comparisons. RESULTS: There were 219 patients (mean age 51 ± 13 y; 82.5% women). Thirty-six patients (16.4%) had MBL ≤50 ng/mL. Two MBL measurements were available in 14 patients. The median interval between the first and second measurements was 125 d (range 18-1031). For ln-transformed data, we observed adjusted r2 = 0.9675; Pearson correlation coefficient 0.9849; and p < 0.0001. Characteristics of patients with and without MBL ≤50 ng/mL did not differ significantly in univariate comparisons. We performed a regression on MBL ≤50 ng/mL using: subnormal IgM (p = 0.0565); upper respiratory tract infection (p = 0.1094); and body mass index (p = 0.1865). This regression revealed no significant associations. CONCLUSIONS: We conclude that the proportion of the present IgGSD patients with serum MBL ≤50 ng/mL is similar to that of healthy European adults. MBL ≤50 ng/mL was not significantly associated with independent variables we studied.


Assuntos
Doenças Autoimunes/epidemiologia , Deficiência de IgG/epidemiologia , Imunoglobulina G/genética , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/deficiência , Erros Inatos do Metabolismo/epidemiologia , Infecções Respiratórias/epidemiologia , Adulto , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Risco , Estados Unidos/epidemiologia
2.
Medicine (Baltimore) ; 98(22): e15928, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145360

RESUMO

Congenital chloride losing diarrhea (CCLD) is a rare type of chronic watery diarrhea due to mutations in SLC26A3 gene leading to defective chloride-bicarbonate exchanges with the resultant loss of chloride and retention of bicarbonate.We aim to define pediatric Saudi CCLD patients' characteristics to achieve prompt diagnosis, management, follow up with good quality of life, and prevention of complications in these patients.We carried retrospective data review of demographic, clinical, laboratory, radiographic, and outcome of all pediatric patients fulfilling the criteria of CCLD over 10 years from 2004 to 2014 from a single center in Taif region, Saudi Arabia.Forty-nine patients fulfilled the criteria of CCLD from 21 families with more than one affected patient in the same family in 90% of them and positive consanguinity in 91% of the cohort. Most patients were born preterm with intrauterine growth restriction and usually neonatal intensive care unit (NICU) admissions with prematurity and its complications. Thirteen patients were discharged without diagnosis of CCLD and 3 were misdiagnosed as intestinal obstruction with unnecessary surgical intervention. Many complications do existed with renal complications being the most common with three patients received renal transplantation.Prematurity with abdominal distension and stool like urine were the commonest presentation of CCLD in Saudi children. Positive consanguinity and more than one affected sibling are present in most of our cohort.High index of suspicion by clinicians is a cornerstone for early diagnosis with subsequent favorable outcome.A multicenter national incidence study of CCLD in KSA and its genetic attributes is recommended. Premarital screening should be implemented specially for consanguineous marriage.


Assuntos
Diarreia/congênito , Doenças do Prematuro/epidemiologia , Erros Inatos do Metabolismo/epidemiologia , Consanguinidade , Diarreia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Estudos Retrospectivos , Arábia Saudita/epidemiologia
3.
Orphanet J Rare Dis ; 14(1): 84, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023387

RESUMO

Methylmalonic acidemia/aciduria (MMA) is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid. Isolated MMA is primarily caused by the deficiency of methylmalonyl-CoA mutase (MMA mut; EC 5.4.99.2). A systematic literature review and a meta-analysis were undertaken to assess and compile published epidemiological data on MMA with a focus on the MMA mut subtype (OMIM #251000). Of the 1114 identified records, 227 papers were assessed for eligibility in full text, 48 articles reported on disease epidemiology, and 39 articles were included into the quantitative synthesis. Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. Meta-analysis pooled point estimates of MMA (all types) detection rates were 0.79, 1.12, 1.22 and 6.04 per 100,000 newborns in Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. The detection rate of isolated MMA was < 1 per 100,000 newborns in all regions with the exception of MENA where it approached 6 per 100,000 newborns. Few studies published data on the epidemiology of MMA mut, therefore no meta-analysis could have been performed on this subtype. Most of the identified papers reported birth prevalence estimates below 1 per 100,000 newborns for MMA mut. The systematic literature review clearly demonstrates that MMA and its subtypes are ultra-rare disorders.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Metilmalonil-CoA Mutase/genética , Erros Inatos do Metabolismo dos Aminoácidos/genética , Feminino , Humanos , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/enzimologia , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/genética , Metilmalonil-CoA Mutase/deficiência , Triagem Neonatal
4.
Artigo em Inglês | MEDLINE | ID: mdl-30854980

RESUMO

BACKGROUND: In the last decades, both diabetes mellitus and Alzheimer's disease are constantly increasing. Affected individuals, therefore, represent an enormous problem for the society, governments and global organizations. These diseases are usually considered as independent conditions, but increasing evidence shows that there are links between these two disorders. METHODS: In this review, we analyzed common features present in Alzheimer's disease and diabetes mellitus, showing how these two diseases are strictly correlated to each other. RESULTS: Some pathogenetic factors are shared by Type 2 Diabetes and Alzheimer's Disease: chronic inflammation, oxidative stress, mitochondrial dysfunction, adiponectin deficiency, different expression of plasma cholinesterase activity and vascular damage could represent a possible explanation for the coexistence of these two conditions in many patients. CONCLUSION: A better understanding of this issue and an appropriate management of diabetes by means of physical activity, low fat diet, and drugs to achieve a good glycemic control, avoiding both hyperglycemia and hypoglycemia, can represent a way to prevent cognitive decline and Alzheimer's disease.


Assuntos
Doença de Alzheimer/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Adiponectina/deficiência , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Inflamação/psicologia , Inflamação/terapia , Resistência à Insulina/fisiologia , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/terapia , Estresse Oxidativo/fisiologia , Fatores de Risco
5.
East Mediterr Health J ; 24(11): 1103-1111, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30701526

RESUMO

Background: Although inborn errors of metabolism (IEM) are rare individually, collectively IEM cause substantial morbidity and mortality and the diagnosis is challenging. Aims: To analyse epidemiological and clinical data, final diagnosis and clinical outcomes of patients with a suspected diagnosis of IEM (small molecule disorders type) admitted to a paediatric intensive care unit (PICU). Methods: We collected and analysed medical records data of all patients admitted to the PICU at Alexandria University Children's Hospital, from January 2010 to December 2014, with a suspected or confirmed diagnosis of small molecule disorders, including clinical presentations, laboratory results and clinical outcomes. Results: A total of 34 patients had a suspected or confirmed diagnosis of small molecule disorders at PICU admission. Diagnosis was confirmed in 22.7% of suspected cases at admission and in 25% of suspected cases during PICU stay. Consanguineous marriage was found in 50% of cases with confirmed small molecule disorders. Conclusions: A high index of suspicion is important for diagnosing and categorizing small molecule disorders in screening of high-risk individuals in low- and middle-income countries.


Assuntos
Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Erros Inatos do Metabolismo/epidemiologia , Criança , Pré-Escolar , Consanguinidade , Egito/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/etiologia , Erros Inatos do Metabolismo/mortalidade , Estudos Retrospectivos , Fatores de Risco
6.
Orphanet J Rare Dis ; 14(1): 40, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760309

RESUMO

Propionic acidemia (PA, OMIM #606054) is a serious, life-threatening, inherited, metabolic disorder caused by the deficiency of the mitochondrial enzyme propionyl-coenzyme A (CoA) carboxylase (EC 6.4.1.3). The primary objective of this study was to conduct a systematic literature review and meta-analysis on the epidemiology of PA. The literature search was performed covering Medline, Embase, Cochrane Database of Systematic Reviews, CRD Database, Academic Search Complete, CINAHL and PROSPERO databases. Websites of rare disease organizations were also searched for eligible studies. Of the 2338 identified records, 188 articles were assessed for eligibility in full text, 43 articles reported on disease epidemiology, and 31 studies were included into the quantitative synthesis. Due to the rarity of PA, broadly targeted population-based prevalence studies are not available. Nonetheless, implementation of newborn screening programs has allowed the estimation of the birth prevalence data of PA across multiple geographic regions. The pooled point estimates indicated detection rates of 0.29; 0.33; 0.33 and 4.24 in the Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. Our systematic literature review and meta-analysis confirm that PA is an ultra-rare disorder, with similar detection rates across all regions with the exception of the MENA region where the disease, similar to other inherited metabolic disorders, is more frequent.


Assuntos
Acidemia Propiônica/diagnóstico , Acidemia Propiônica/epidemiologia , Humanos , Recém-Nascido , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/epidemiologia , Triagem Neonatal/métodos
7.
Biochim Biophys Acta Mol Basis Dis ; 1865(1): 48-55, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30343140

RESUMO

The prevalence of cardiometabolic disease has reached an exponential rate of rise over the last decades owing to high fat/high caloric diet intake and satiety life style. Although the presence of dyslipidemia, insulin resistance, hypertension and obesity mainly contributes to the increased incidence of cardiometabolic diseases, population-based, clinical and genetic studies have revealed a rather important role for inherited myopathies and endocrine disorders in the ever-rising metabolic anomalies. Inherited metabolic and endocrine diseases such as glycogen storage and lysosomal disorders have greatly contributed to the overall prevalence of cardiometabolic diseases. Recent evidence has demonstrated an essential role for proteotoxicity due to autophagy failure and/or dysregulation in the onset of inherited metabolic and endocrine disorders. Given the key role for autophagy in the degradation and removal of long-lived or injured proteins and organelles for the maintenance of cellular and organismal homeostasis, this mini-review will discuss the potential contribution of autophagy dysregulation in the pathogenesis of inherited myopathies and endocrine disorders, which greatly contribute to an overall rise in prevalence of cardiometabolic disorders. Molecular, clinical, and epidemiological aspects will be covered as well as the potential link between autophagy and metabolic anomalies thus target therapy may be engaged for these comorbidities.


Assuntos
Autofagia , Doenças do Sistema Endócrino/metabolismo , Erros Inatos do Metabolismo/metabolismo , Doenças Musculares/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças do Sistema Endócrino/epidemiologia , Glicogênio , Homeostase , Humanos , Resistência à Insulina , Lisossomos/metabolismo , Síndrome Metabólica/metabolismo , Erros Inatos do Metabolismo/epidemiologia , Doenças Musculares/epidemiologia , Obesidade/metabolismo
8.
J Clin Neurosci ; 59: 32-36, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30455135

RESUMO

Wide spectrums of symptoms besides muscle weakness, different triggering factors and varied muscles involvement are associated with CPT II deficiency. However, systematic clinical characterization of CPT II deficiency is not known. A Questionnaire-based retrospective study on 13 biochemically and genetically confirmed CPT II deficient patients was performed to analyze these aspects. Attacks of myalgia (13/13 patients), weakness (13/13) and rhabdomyolysis (10/13 patients) were most frequently reported. The number of attacks ranged from 1 to 85/year. Common triggers were exercise (13/13), fasting (13/13), cold (12/13) and infections (12/13). Exercise lasting from 15 to 60 min was sufficient for attacks in 9/13 patients, 1-4 h in 3/13 patients and more than 4 h in 1/13 patient. 2/13 patients required dialysis. Limb muscles were affected slightly more often than other muscles. Mean intensity of pain in visual analogue scale (VAS) during regular attack was 4.77 (±1.36). Frequency and severity of attacks did not increase during the course of disease in 10/13 patients. 7/13 patients quit sports after the symptoms emerged. 3/13 patients changed their profession permanently. Increased number of attacks were positively correlated with higher BMI (P = 0.05). Body rest, carbohydrate-rich nutrients and fluid-supplement mitigated the pain. After the first attack [Mean: 9.7 (±4.46) years], diagnosis took an average of 26.7 (± 13.06) years. In myopathic CPT II deficiency, frequencies of attacks are highly variable. Generally, the myopathic form is a mild form. However, severe patients requiring dialysis due to kidney failure could be present. Individuals with higher BMI are at risk of developing more frequent attacks.


Assuntos
Carnitina O-Palmitoiltransferase/deficiência , Erros Inatos do Metabolismo/diagnóstico , Fenótipo , Adolescente , Criança , Exercício , Feminino , Humanos , Masculino , Erros Inatos do Metabolismo/epidemiologia , Debilidade Muscular/epidemiologia , Rabdomiólise/epidemiologia , Inquéritos e Questionários
9.
Eur J Obstet Gynecol Reprod Biol ; 232: 87-96, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30502592

RESUMO

BACKGROUND: Consanguinity is the close union, sexual relationship or marriage between persons who have common biological ancestors usually up to about 2nd cousins. Contrary to general opinion consanguinity is quite common and is practiced worldwide. It is an important topic as while rates of consanguineous unions in certain society have decreased over time, rates have remained stable or increased in other societies with rates as high as 80.6% in some communities. Our aim was to conduct a review looking at general aspects of consanguinity and any published reproductive outcomes in literature. We also looked at possible future directions that could be relevant in the management of the consanguineous couple to help improve reproductive outcomes. METHOD: We conducted a PUBMED, CINAHL, Web of Knowledge and Google Scholar search looking at articles on consanguinity. Consanguinity articles related to pregnancy and reproduction were searched using additional filters looking at our specific areas of interest. All relevant publications up to March 2015 were reviewed. Additional search for relevant articles pertaining to pre implantation genetic diagnosis for future directions in the management of the consanguineous couple was done. Most publications were found in books, on line articles and journals. Most were retrospective, population or cohort studies. RESULT: Consanguinity is practiced by up to 10% of the world's population with rates ranging from 80.6% in certain provinces in the Middle East to less than 1% in western societies. It predates Islam and has been practiced since Old Testament times. The most commonly cited reason for consanguinity is sociocultural and socioeconomic although it is also more common in certain religions. In areas where rates of Consanguinity are reducing urban migration and increasing education rates are thought to be contributory. Congenital malformations have long been established to be higher in consanguineous couples above the background rate (4.5% Vs 1%).Due to "Founder effect" or a common ancestor, Consanguinity is most commonly associated with Inborn errors of metabolism most of which are autosomal recessive. Consanguinity increases the incidence of multifactorial disorders such as diabetes, cardiovascular disorders, obesity and certain types of cancers. These may in turn affect reproductive outcomes. It may also affect fertility rates. Pregnancy outcomes like increased pregnancy wastages and preterm labor have been reported with consanguinity. Other studies produced conflicting evidence on its effect regarding outcomes like hypertensive disorders of pregnancy and Intrauterine growth restriction. CONCLUSION: Consanguinity continues to be practiced worldwide and in some countries rates are increasing. The main reason for the practice appears to be sociocultural and socioeconomic although religious beliefs is a contributory factor. The most significant effects on reproductive outcomes are mostly due to autosomal recessive inherited conditions and inborn errors of metabolism. It also significantly increases the inheritance of certain multifactorial disorders like diabetes which may indirectly affect reproductive outcomes. In the future with the completion of the study of the whole human Genome and current advances in Pre implantation Genetic diagnosis and screening it may be possible to mitigate some of the adverse reproductive outcomes associated with consanguinity.


Assuntos
Consanguinidade , Fertilidade , Erros Inatos do Metabolismo/etiologia , Resultado da Gravidez , Feminino , Humanos , Incidência , Masculino , Idade Materna , Erros Inatos do Metabolismo/epidemiologia , Gravidez
10.
Arch Dis Child Fetal Neonatal Ed ; 104(5): F493-F501, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30472660

RESUMO

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171.


Assuntos
Eletroencefalografia/métodos , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Erros Inatos do Metabolismo , Convulsões , Acidente Vascular Cerebral , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/epidemiologia , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/terapia , Masculino , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/epidemiologia , Monitorização Fisiológica/métodos , Exame Neurológico/estatística & dados numéricos , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/etiologia , Convulsões/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
11.
Genet Med ; 20(12): 1499-1507, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30459394

RESUMO

Amino acid abnormalities are observed in a broad spectrum of inherited metabolic diseases, such as disorders of amino acid metabolism and transport, organic acidemias, and ureagenesis defects. Comprehensive analysis of physiologic amino acids in blood, urine, and cerebrospinal fluid is typically performed in the following clinical settings: evaluation of symptomatic patients in whom a diagnosis is not known; evaluation of previously diagnosed patients to monitor treatment efficacy; evaluation of asymptomatic or presymptomatic (at-risk) relatives of known patients; follow-up testing for an abnormal newborn screen; and assessment of dietary protein adequacy or renal function in general patient populations. Currently, the most common analytical method to quantify amino acids is based on ion exchange chromatography using post-column derivatization with ninhydrin and spectrophotometric detection. Newer methodologies are based on liquid chromatographic separation with detection by mass spectrometry or spectrophotometry. Amino acid analysis by nonseparation methods, such as the flow injection-tandem mass spectrometric (MS/MS) method used for newborn screening, is considered inadequate for the diagnosis of at-risk patients. The purpose of this document is to provide a technical standard for amino acid analysis as applied to the diagnosis and management of inborn errors of metabolism.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Aminoácidos/genética , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Aminoácidos/sangue , Cromatografia Líquida , Genética Médica/normas , Genômica , Humanos , Recém-Nascido , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/genética , Triagem Neonatal/normas , Espectrometria de Massas em Tandem , Estados Unidos/epidemiologia
12.
J Glob Health ; 8(2): 021102, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30479748

RESUMO

Background: Inborn errors of metabolism (IEM) are a group of over 500 heterogeneous disorders resulting from a defect in functioning of an intermediate metabolic pathway. Individually rare, their cumulative incidence is thought to be high, but it has not yet been estimated globally. Although outcomes can often be good if recognised early, IEM carry a high fatality rate if not diagnosed. As a result, IEM may contribute significantly to the burden of non-communicable childhood morbidity. Methods: We conducted a systematic literature review of birth prevalence and case fatality of IEM globally, with search dates set from 1980 to 2017. Using random-effects meta-analysis, we estimated birth prevalence of separate classes of IEM and all-cause IEM, split by geographical region. We also estimated levels of parental consanguinity in IEM cases and global case fatality rates and resultant child deaths from all-cause IEM. Findings: 49 studies met our selection criteria. We estimate the global birth prevalence of all-cause IEM to be 50.9 per 100 000 live births (95% confidence intervals (CI) = 43.4-58.4). Regional pooled birth prevalence rates showed the highest rates of IEM to be in the Eastern Mediterranean region (75.7 per 100 000 live births, 95% CI = 50.0-101.4), correlating with a higher observed rate of parental consanguinity in studies from this area. We estimate case fatality rates to be 33% or higher in low- and middle-income countries (LMICs), resulting in a minimum of 23 529 deaths from IEM per year globally (95% CI = 20 382-27 427), accounting for 0.4% of all child deaths worldwide. Conclusions: IEM represent a significant cause of global child morbidity and mortality, comprising a notable proportion of child deaths currently not delineated in global modelling efforts. Our data highlight the need for policy focus on enhanced laboratory capacity for screening and diagnosis, community interventions to tackle parental consanguinity, and increased awareness and knowledge regarding management of IEM, particularly in LMICs.


Assuntos
Saúde Global/estatística & dados numéricos , Erros Inatos do Metabolismo/epidemiologia , Humanos , Erros Inatos do Metabolismo/mortalidade , Prevalência
13.
Orphanet J Rare Dis ; 13(1): 141, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115094

RESUMO

The use of specialized centers has been the main alternative for an appropriate diagnosis, management and follow up of patients affected by inborn errors of metabolism (IEM). These centers facilitate the training of different professionals, as well as the research at basic, translational and clinical levels. Nevertheless, few reports have described the experience of these centers and their local and/or global impact in the study of IEM. In this paper, we describe the experience of a Colombian reference center for the research, diagnosis, training and education on IEM. During the last 20 years, important advances have been achieved in the clinical knowledge of these disorders, as well as in the local availability of several diagnosis tests. Organic acidurias have been the most frequently detected diseases, followed by aminoacidopathies and peroxisomal disorders. Research efforts have been focused in the production of recombinant proteins in microorganisms towards the development of new enzyme replacement therapies, the design of gene therapy vectors and the use of bioinformatics tools for the understanding of IEM. In addition, this center has participated in the education and training of a large number professionals at different levels, which has contributed to increase the knowledge and divulgation of these disorders along the country. Noteworthy, in close collaboration with patient advocacy groups, we have participated in the discussion and construction of initiatives for the inclusion of diagnosis tests and treatments in the health system.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Colômbia/epidemiologia , Humanos , Erros Inatos do Metabolismo/epidemiologia , Doenças Raras/diagnóstico , Doenças Raras/epidemiologia
14.
Curr Opin Urol ; 28(5): 414-419, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29957682

RESUMO

PURPOSE OF REVIEW: To summarize the latest findings of congenital and acquired diseases related to stone formation and help understanding the multitude of cofactors related to urolithiasis. RECENT FINDINGS: Urolithiasis is related to a broad spectrum of congenital and acquired diseases and its management varies according to the stone type, underlying disease or recurrence rate, but it also changes according to recent findings and developments. As prevalence of urolithiasis is constantly increasing, identification of high-risk stone formers and early treatment is essential. Therefore, genetic evaluation like whole exome sequencing becomes a pertinent part of further diagnostics. SUMMARY: Stone formation is a very heterogeneous pathomechanism. This prompt us to look at every patient individually particularly in high-risk patients, including stone and 24-h-urine analysis and additional diagnostic work-up based on stone type or underlying disease.


Assuntos
Urolitíase/epidemiologia , Acidose Tubular Renal/epidemiologia , Adenina Fosforribosiltransferase/deficiência , Fibrose Cística/epidemiologia , Cistinúria/epidemiologia , Doença de Dent/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Hiperoxalúria Primária/epidemiologia , Hiperparatireoidismo/epidemiologia , Imobilização/estatística & dados numéricos , Doenças Inflamatórias Intestinais/epidemiologia , Síndrome de Lesch-Nyhan/epidemiologia , Síndrome Metabólica/epidemiologia , Erros Inatos do Metabolismo/epidemiologia , Nefrocalcinose/epidemiologia , Doenças Renais Policísticas/epidemiologia , Fatores de Risco , Sarcoidose/epidemiologia , Traumatismos da Medula Espinal/epidemiologia , Bexiga Urinaria Neurogênica/epidemiologia , Infecções Urinárias/epidemiologia , Xantina Desidrogenase/deficiência
15.
Artigo em Inglês | MEDLINE | ID: mdl-29723117

RESUMO

Hereditary xanthinuria (type I) is caused by an inherited deficiency of the xanthine oxidorectase (XDH/XO), and is characterized by very low concentration of uric acid in blood and urine and high concentration of urinary xanthine, leading to urolithiasis. Type II results from a combined deficiency of XDH/XO and aldehyde oxidase. Patients present with hematuria, renal colic, urolithiasis or even acute renal failure. Clinical symptoms are the same for both types. In a third type, clinically distinct, sulfite oxidase activity is missing as well as XDH/XO and aldehyde oxidase. The prevalence is not known, but about 150 cases have been described so far. Hypouricemia is sometimes overlooked, that´s why we have set up the diagnostic flowchart. This consists of a) evaluation of uric acid concentrations in serum and urine with exclusion of primary renal hypouricemia, b) estimation of urinary xanthine, c) allopurinol loading test, which enables to distinguish type I and II; and finally assay of xanthine oxidoreductase activity in plasma with molecular genetic analysis. Following this diagnostic procedure we were able to find first patients with hereditary xanthinuria in our Czech population. We have detected nine cases, which is one of the largest group worldwide. Four patients were asymptomatic. All had profound hypouricemia, which was the first sign and led to referral to our department. Urinary concentrations of xanthine were in the range of 170-598 mmol/mol creatinine (normal < 30 mmol/mol creatinine). Hereditary xanthinuria is still unrecognized disorder and subjects with unexplained hypouricemia need detailed purine metabolic investigation.


Assuntos
Aldeído Oxidase/deficiência , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo da Purina-Pirimidina/epidemiologia , Purinas/metabolismo , Xantina Desidrogenase/deficiência , Xantina Desidrogenase/metabolismo , Adulto , Aldeído Oxidase/sangue , Aldeído Oxidase/urina , Alopurinol/metabolismo , Criança , Pré-Escolar , República Tcheca/epidemiologia , Diagnóstico Diferencial , Humanos , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/urina , Erros Inatos do Metabolismo da Purina-Pirimidina/sangue , Erros Inatos do Metabolismo da Purina-Pirimidina/diagnóstico , Erros Inatos do Metabolismo da Purina-Pirimidina/urina , Erros Inatos do Transporte Tubular Renal/sangue , Erros Inatos do Transporte Tubular Renal/epidemiologia , Erros Inatos do Transporte Tubular Renal/urina , Ácido Úrico/sangue , Ácido Úrico/urina , Cálculos Urinários/sangue , Cálculos Urinários/epidemiologia , Cálculos Urinários/urina , Xantina/sangue , Xantina/urina , Xantina Desidrogenase/sangue , Xantina Desidrogenase/urina
16.
Indian J Pediatr ; 85(12): 1110-1117, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29736696

RESUMO

Inborn errors of metabolism (IEM) are a heterogeneous group of genetic disorders that cause significant neonatal and infant mortality. Expanded newborn screening which detects these disorders at birth is the standard preventive strategy in most countries. Prospective studies to evaluate the impact of these in the Indian population are lacking. The imminent need to address this lacuna warrants a review of available pan India data, as well as efforts for a carefully conducted prospective assessment of the burden of IEM. Published data on IEM in the Indian population comprising universal prospective screening and screening in selected subgroups (patients admitted to pediatric/neonatal ICUs, patients with developmental delay/mental retardation) was collected through a systematic search. The primary focus was to get an estimate of the disease burden in the Indian population. A true prevalence of IEM in India is not available. The systematic review identifies and stratifies the various situations where IEM are found. Data collected by universal screening of the low risk population is essential to identify the true prevalence of IEM in India.


Assuntos
Erros Inatos do Metabolismo/epidemiologia , Triagem Neonatal , Humanos , Índia/epidemiologia , Recém-Nascido , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/prevenção & controle , Prevalência
17.
J Pediatr Hematol Oncol ; 40(5): 355-359, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29746437

RESUMO

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.


Assuntos
Doenças Hematológicas/epidemiologia , Doenças Hematológicas/etiologia , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
18.
Scand J Immunol ; 88(1): e12675, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29758096

RESUMO

Chronic inflammation has been implicated as the underlying mechanism responsible for the pathophysiology of preterm labour. Mannose-binding lectin (MBL) plays a central role in the innate immune response and is thus an important component of the first line of defense. The aim of this study was to investigate whether serum concentrations of MBL correlated with the incidence of preterm birth and low birthweight in a cohort of women with signs of threatened preterm birth. A cohort of 60 patients who presented with regular contractions and/or short cervix (group A) between 24 and 32 weeks of gestation and 20 healthy controls (group B) who had no pregnancy complications and delivered at term were recruited into a prospective study. The following outcomes were recorded: presence of preterm labour and birthweight in all patients. MBL and high sensitivity C-reactive protein levels were measured in all serum samples. The serum concentrations of MBL were significantly reduced in patients with threatened preterm labour (Group A), compared to the control Group B. Furthermore, infants born to Group A mothers with MBL deficiency (n = 13, MBL ≤100 ng/mL) had significantly lower birthweights, compared to those born to Group A women with normal MBL serum concentrations (P < .0001). Our small cohort study demonstrated a strong association between MBL deficiency and preterm delivery, and associated low birthweight. MBL deficiency could thus be considered an important risk factor for preterm birth.


Assuntos
Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/deficiência , Erros Inatos do Metabolismo/complicações , Trabalho de Parto Prematuro/sangue , Nascimento Prematuro/sangue , Adulto , Biomarcadores/sangue , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Erros Inatos do Metabolismo/epidemiologia , Gravidez , Estudos Prospectivos , Fatores de Risco
19.
Neurosciences (Riyadh) ; 23(2): 97-103, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29664449

RESUMO

Both malformations of the central nervous system and neurometabolic disorders are common, mainly in highly consanguineous populations. Both metabolic pathways and developmental pathways are closely related and interact with each other. Neurometabolic disorders can lead to disturbances in brain development through multiple mechanisms that include deficits in energy metabolism, critical nutrient deficiency, accumulation of neurotoxic substrates, abnormality in cell membrane constituents, and interference in cell-to-cell signaling pathways. The anomalies observed include absent or hypoplastic corpus callosum, midline brain defects, and malformations of the cortex, the cerebellum and the brain stem. Early diagnosis of an underlying inherited neurometabolic disorders is critical for the institution of treatment, which may positively influence prognosis, and allow for proper genetic counseling. In this review, we discuss those disorders in which the structural brain malformation is a dominant feature, and propose a practical approach that will permit a physician to investigate, and treat these disorders.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Malformações do Sistema Nervoso/diagnóstico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/terapia , Malformações do Sistema Nervoso/complicações , Malformações do Sistema Nervoso/terapia
20.
BMC Pediatr ; 18(1): 110, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29534692

RESUMO

BACKGROUND: Mandatory newborn screening for metabolic disorders has not been implemented in most parts of China. Newborn mortality and morbidity could be markedly reduced by early diagnosis and treatment of inborn errors of metabolism (IEM). Methods of screening for IEM by tandem mass spectrometry (MS/MS) have been developed, and their advantages include rapid testing, high sensitivity, high specificity, high throughput, and low sample volume (a single dried blood spot). METHODS: Dried blood spots of 100,077 newborns obtained from Jining city in 2014-2015 were screened by MS/MS. The screening results were further confirmed by clinical symptoms and biochemical analysis in combination with the detection of neonatal deficiency in organic acid, amino acid, or fatty acid metabolism and DNA analysis. RESULTS: The percentages of males and females among the 100,077 infants were 54.1% and 45.9%, respectively. Cut-off values were established by utilizing the percentile method. The screening results showed that 98,764 newborns were healthy, and 56 out of the 1313 newborns with suspected IEM were ultimately diagnosed with IEM. Among these 56 newborns, 19 (1:5267) had amino acid metabolism disorders, 26 (1:3849) had organic acid metabolism disorders, and 11 (1:9098) had fatty acid oxidation disorders. In addition, 54 patients with IEM were found to carry mutations, and the other 2 patients had argininemia. CONCLUSIONS: Fifty-six cases of metabolic disorders in Jining were confirmed via newborn screening (NBS) by MS/MS. Early diagnosis and treatment are crucial for the survival and well-being of affected children. A nationwide NBS program using MS/MS is recommended, especially in poor areas of China.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , China/epidemiologia , Teste em Amostras de Sangue Seco , Diagnóstico Precoce , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/terapia , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
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