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1.
Pediatrics ; 145(3)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32034080

RESUMO

Successful intervention for inborn errors of metabolism (IEMs) is a triumph of modern medicine. For many of these conditions, medical foods are the cornerstone of therapy and the only effective interventions preventing disability or death. Medical foods are designed for patients with limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foods or nutrients, whereby dietary management cannot be achieved by modification of the normal diet alone. In the United States today, access to medical foods is not ensured for many individuals who are affected despite their proven efficacy in the treatment of IEMs, their universal use as the mainstay of IEM management, the endorsement of their use by professional medical organizations, and the obvious desire of families for effective care. Medical foods are not sufficiently covered by many health insurance plans in the United States and, without insurance coverage, many families cannot afford their high cost. In this review, we outline the history of medical foods, define their medical necessity, discuss the barriers to access and reimbursement resulting from the regulatory status of medical foods, and summarize previous efforts to improve access. The Advisory Committee on Heritable Disorders in Newborns and Children asserts that it is time to provide stable and affordable access to the effective management required for optimal outcomes through the life span of patients affected with IEMs. Medical foods as defined by the US Food and Drug Administration should be covered as required medical benefits for persons of all ages diagnosed with an IEM.


Assuntos
Dieta , Suplementos Nutricionais , Erros Inatos do Metabolismo/dietoterapia , Suplementos Nutricionais/economia , Acesso aos Serviços de Saúde , Humanos , Recém-Nascido , Cobertura do Seguro/legislação & jurisprudência , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Estados Unidos
2.
Eur J Endocrinol ; 182(2): R15-R27, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31995340

RESUMO

Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, and recruitment of functional transcriptional machinery. Generalized glucocorticoid resistance syndrome, due to GR loss-of-function mutations, may be related to the impairment of one of the GC signaling steps. To date, 31 NR3C1 loss-of-function mutations have been reported in patients presenting with various clinical signs such as hypertension, adrenal hyperplasia, hirsutism or metabolic disorders associated with biological hypercortisolism but without Cushing syndrome signs and no negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Functional characterization of GR loss-of-function mutations often demonstrates GR haploinsufficiency and a decrease of GR target gene induction in relevant cell types. The main signs at presentation are very variable from resistant hypertension, bilateral adrenal hyperplasia likely related to increased ACTH levels but not exclusively, hirsutism to isolated renin-angiotensin-aldosterone system abnormalities in a context of 11ßHSD2 deficiency. Some mutated GR patients are obese or overweight together with a healthier metabolic profile that remains to be further explored in future studies. Deciphering the molecular mechanisms altered by GR mutations should enhance our knowledge on GR signaling and ultimately facilitate management of GC-resistant patients. This review also focuses on the criteria facilitating identification of novel NR3C1 mutations in selected patients.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Receptores de Glucocorticoides/deficiência , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/genética , Glucocorticoides/sangue , Glucocorticoides/genética , Humanos , Hidrocortisona/sangue , Hidrocortisona/genética , Erros Inatos do Metabolismo/sangue , Receptores de Glucocorticoides/sangue , Receptores de Glucocorticoides/genética
3.
Adv Clin Chem ; 94: 85-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31952575

RESUMO

Metabolomics is an intriguing field of study providing a new readout of the biochemical activities taking place at the moment of sampling within a subject's biofluid or tissue. Metabolite concentrations are influenced by several factors including disease, environment, drugs, diet and, importantly, genetics. Metabolomics signatures, which describe a subject's phenotype, are useful for disease diagnosis and prognosis, as well as for predicting and monitoring the effectiveness of treatments. Metabolomics is conventionally divided into targeted (i.e., the quantitative analysis of a predetermined group of metabolites) and untargeted studies (i.e., analysis of the complete set of small-molecule metabolites contained in a biofluid without a pre-imposed metabolites-selection). Both approaches have demonstrated high value in the investigation and understanding of several monogenic and multigenic conditions. Due to low costs per sample and relatively short analysis times, metabolomics can be a useful and robust complement to genetic sequencing.


Assuntos
Testes Genéticos , Metabolômica , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Fenótipo
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1067-1072, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703127

RESUMO

OBJECTIVE: To determine the incidence and mutational types of fatty acid oxidation disorders (FAOD) in central-northern region of Guangxi. METHODS: A total of 62 953 neonates were screened for FAOD during December 2012 and December 2017. Acyl-carnitine profiling of neonatal blood sample was performed by tandem mass spectrometry using dry blood spots on a filter paper. The diagnosis of FAOD was confirmed by organic acid profiling of urea and genetic testing. RESULTS: Eighteen cases of FAOD were diagnosed among the 62 953 neonates. Among these, primary carnitine deficiency (PCD) was the most common type (n=13), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD) (n=2), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) (n=1), multiple acyl-CoA dehydrogenase deficiency (MADD) (n=1), and carnitine palmitoyltransferase II deficiency (CPT II D) (n=1). Genetic testing has revealed two previously unreported variants, i.e., c.337G to A (p.Gly113Arg) of ACADS gene and c.737G TO T (p.Gly246Val) of ETFA gene. CONCLUSION: PCD is the most common FAOD in central-northern Guangxi. Tandem mass spectrometry combined with genetic testing may facilitate early diagnosis of FAOD.


Assuntos
Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Acil-CoA Desidrogenase/deficiência , Acil-CoA Desidrogenase/genética , Carnitina/sangue , Carnitina O-Palmitoiltransferase/deficiência , China , Flavoproteínas Transferidoras de Elétrons/genética , Humanos , Recém-Nascido , Erros Inatos do Metabolismo/diagnóstico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico , Triagem Neonatal , Espectrometria de Massas em Tandem
5.
Adv Clin Chem ; 92: 59-103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31472756

RESUMO

Inborn errors of metabolism (IEMs) are a large class of genetic disorders that result from defects in enzymes involved in energy production and metabolism of nutrients. For every metabolic pathway, there are defects that can occur and potentially result in an IEM. While some defects can go undetected in one's lifetime, some have moderate to severe clinical consequences. In the latter case, the biochemical defect leads to accumulation of metabolites and byproducts that are toxic or interfere with normal biological function. Disorders of amino acid metabolism, organic acid metabolism and the urea cycle comprise a large portion of IEMs. Two essential tools required for the diagnosis of these categories of disorders are amino acid and organic acid profiling. Most all clinical laboratories offering metabolic testing perform amino acid analysis, while organic acid profiling is restricted to more specialized pediatric hospitals and reference laboratories. In this chapter, we will provide an overview of various methodologies employed for amino acid and organic acid profiling as well as specific examples to demonstrate how these techniques are applied in clinical laboratories for the diagnosis of IEMs.


Assuntos
Aminoácidos/análise , Ácidos Carboxílicos/análise , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/metabolismo , Humanos
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 870-873, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515778

RESUMO

OBJECTIVE: To assess the value of dry blood spot tandem mass spectrometry for the diagnosis of autism spectrum disorder (ASD). METHODS: Peripheral blood samples of 277 autistic children were collected. Their amino acid and carnitine profiles were detected by liquid chromatography tandem mass spectrometry. Urine samples of suspected patients were collected for verification by gas chromatography mass spectrometry. Blood samples were also taken for genetic testing. RESULTS: Of the 277 children with ASD, 19 (6.9%) were suspected to be with inborn error of metabolism (IEM), which included 6 cases with amino acidemia, 9 with organic acidemia and 4 with fatty acidemia. Three cases of phenylketonuria, one case of homocysteinemia, one case of propionemia, one case of methylmalonic acidemia, one case of glutaric acidemia, one case of isovaleric acidemia, one case of argininemia, one case of citrullinemia I and four cases of primary carnitine deficiency were confirmed by genetic testing, which yielded an overall diagnostic rate of 5.1% (14/277). CONCLUSION: Our result has provided further evidence for the co-occurrence of ASD and IEM. Tandem mass spectrometry has a great value for the diagnosis and treatment of ASD in childhood.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Transtorno do Espectro Autista/complicações , Criança , Teste em Amostras de Sangue Seco , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Erros Inatos do Metabolismo/complicações , Espectrometria de Massas em Tandem
8.
Eur J Med Genet ; 62(10): 103712, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31276831

RESUMO

Congenital Sodium Diarrhea (CSD) due to SLC9A3 mutation is a rare cause of neonatal diarrhea explained by dysfunction of the Na+/H+ antiporter 3 in intestine. To date only 10 patients have been described. We report a male patient with typical antenatal symptoms (polyhydramnios and intestinal dilation) and neonatal diarrhea with fecal sodium and bicarbonates loss. Next generation sequencing revealed a missense homozygous mutation in exon 6 of the SLC9A3 gene (NM_004174.3:c.1039G > A, NP_004165.2:p.Glu347Lys). Oral electrolytes supplements (Sodium and Bicarbonates) allowed a normal growth to the child currently aged twenty months. CSD symptomatology usually begins during third trimester of pregnancy. Antenatal signs are polyhydramnios and diffuse intestinal dilation. Main differential diagnoses are intestinal obstruction and Congenital Chloride Diarrhea. Diarrhea begins from the first days of life and its severity is variable. Based on the report and on the literature we suggest that non syndromic CSD can be detected during third trimester of pregnancy. With adequate electrolytes supplementation good evolution is possible.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Diarreia/congênito , Estudos de Associação Genética , Predisposição Genética para Doença , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Mutação , Trocador 3 de Sódio-Hidrogênio/genética , Sequência de Aminoácidos , Biópsia , Análise Mutacional de DNA , Diagnóstico por Imagem , Diarreia/diagnóstico , Diarreia/genética , Marcadores Genéticos , Humanos , Lactente , Masculino
9.
Handb Clin Neurol ; 162: 449-481, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31324325

RESUMO

Inborn errors of metabolism, also known as inherited metabolic diseases, constitute an important group of conditions presenting with neurologic signs in newborns. They are individually rare but collectively common. Many are treatable through restoration of homeostasis of a disrupted metabolic pathway. Given their frequency and potential for treatment, the clinician should be aware of this group of conditions and learn to identify the typical manifestations of the different inborn errors of metabolism. In this review, we summarize the clinical, laboratory, electrophysiologic, and neuroimaging findings of the different inborn errors of metabolism that can present with florid neurologic signs and symptoms in the neonatal period.


Assuntos
Doenças do Recém-Nascido/terapia , Erros Inatos do Metabolismo/terapia , Adulto , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/diagnóstico por imagem , Doenças do Recém-Nascido/fisiopatologia , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/diagnóstico por imagem , Erros Inatos do Metabolismo/fisiopatologia , Neuroimagem , Gravidez
11.
Saudi J Kidney Dis Transpl ; 30(3): 723-725, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249241

RESUMO

Adenine phosphoribosyltransferase deficiency is an inherited condition presenting from infancy to late adulthood. The common features are recurrent kidney and urinary tract stones and obstructive symptoms. The stones are characteristically radiolucent. 2, 8-Dihydroxyadenine (2, 8-DHA) formation is blocked by xanthine oxidase blocker allopurinol. Here, we report the case of an eight-month-old baby girl who presented with obstructive acute kidney injury secondary to calculi which was treated with surgical removal of stone. The analysis of the calculi revealed 2, 8-DHA crystals.


Assuntos
Lesão Renal Aguda/etiologia , Adenina Fosforribosiltransferase/deficiência , Adenina/análogos & derivados , Cálculos Renais/etiologia , Erros Inatos do Metabolismo/complicações , Urolitíase/complicações , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/cirurgia , Adenina/metabolismo , Alopurinol/uso terapêutico , Cristalização , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Lactente , Cálculos Renais/diagnóstico , Cálculos Renais/metabolismo , Cálculos Renais/cirurgia , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/tratamento farmacológico , Resultado do Tratamento , Urolitíase/diagnóstico , Urolitíase/tratamento farmacológico , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
12.
Medicine (Baltimore) ; 98(19): e15500, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083189

RESUMO

It is required that the clinical screening of metabolic disorders in newborns meet International Organization for Standardization 15189-2012 approval. The new tandem mass spectrometry (MS/MS) based screening system and its companion reagent should be independently authenticated before their implementation in clinical diagnosis laboratories.Linearity, stability, accuracy, and precision evaluations were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase non-derivatized MS/MS PerkinElmer kit for detecting amino acids and acylcarnitine in newborns with metabolic disorders.Statistically, the correlation coefficient (R) of 0.9982 to 0.9999 indicates good linearity. The measurements at the beginning and end of the reagent storage procedure were taken for stability verification. No significant difference was detected between the 2 periods. The amino acid exhibited a degree of bias in the range of 0% to 14.17%, with acylcarnitine's being was in the range of 0% to 14.84%; they consequently passed the quality assessment requirements for clinical laboratories of the China National Centre. The amino acids' within-run, between-run, and day-to-day run precision were 1.19% to 7.68%, 1.63% to 5.01%, and 4.77% to 12.48%, respectively, while the total imprecision was 5.55% to 13.33%. Acylcarnitine's within-run, between-run, and day-to-day run precision was 1.2% to 8.43%, 0.19% to 9.60%, and 2.33% to 10.74%, respectively, while it's total imprecision was 6.57% to 13.99%. The manufacturer declared that the total imprecision of the tests, using Multiple Reaction Monitoring, should be less than or equal to 25% of the coefficient of variation for the kit's high and low-quality control levels.The performance of the non-derivatized MS/MS screening system in detecting the amino acids and acylcarnitines passed the test's requirements. It was maintained in accordance with the routine clinical chemical detection system.


Assuntos
Espectrometria de Massas/métodos , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Humanos , Recém-Nascido
13.
Methods Mol Biol ; 1972: 139-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30847789

RESUMO

Expanded newborn screening of inborn errors of metabolism (IEM) based on tandem mass spectrometry (MS/MS) technology is one of the most successful preventative healthcare initiatives for presymptomatic diagnosis and treatment of rare yet treatable genetic diseases in the population. However, confirmatory testing of presumptive screen-positive cases is required using high efficiency separations for improved specificity in order to improve the positive predictive value (PPV) for certain classes of IEMs. Here, we describe recent advances using capillary electrophoresis-mass spectrometry (CE-MS) for reliable second-tier screening or confirmatory testing based on targeted analysis of amino acids, acylcarnitines, nucleosides, and other classes of polar metabolites associated with IEMs. Additionally, nontargeted metabolite profiling enables the identification of unknown biomarkers of clinical significance for other genetic diseases that are currently screened by bioassays and/or mutation panels, such as cystic fibrosis (CF). Noteworthy, CE-MS allows for resolution of isobaric/isomeric interferences without complicated sample handling that is ideal when analyzing volume-restricted biospecimens from neonates/infants, including dried blood spots and sweat specimens. New developments to improve concentration sensitivity, as well as enhance sample throughput and quality control for unambiguous confirmatory testing of IEMs will also be discussed when using multiplexed separations based on multisegment injection-CE-MS.


Assuntos
Eletroforese Capilar/métodos , Espectrometria de Massas/métodos , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Biomarcadores/sangue , Teste em Amostras de Sangue Seco , Ensaios de Triagem em Larga Escala , Humanos , Recém-Nascido , Metabolômica , Pilocarpina , Controle de Qualidade , Curva ROC , Suor/química
15.
Pediatr Int ; 61(5): 489-494, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30921489

RESUMO

BACKGROUND: In pediatric patients with cholestasis of unknown cause, inborn errors of bile acid (BA) synthesis (IEBAS) may be considered. For the initial screening for IEBAS, clarification of the urine BA profile is essential. The transportation of urine in a frozen state via air delivery, however, is laborious and costly. This study assessed the feasibility of using dried urine spots (DUS) to establish a more convenient and affordable method of IEBAS screening. METHODS: We created DUS using urine samples from patients with 3ß-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase deficiency (3ß-HSD) and Δ4-3-oxo-steroid 5ß-reductase deficiency as standard preparations. We started accepting DUS specimens by regular mail. RESULTS: The ratio of unusual to usual BA is essential for the initial detection of IEBAS, and the recovery rates of abnormal BA were acceptable. The recovery rate of Δ4-BA on day 28 decreased to 31.8% at 25°C, and to 19.6% at 37°C. Therefore, the sending of DUS should be avoided under conditions of high temperature. Of a total of 49 children with cholestasis, eight new patients were diagnosed with IEBAS using this screening method. CONCLUSION: The mailing screening system is expected to facilitate the shipment, from regions outside of Japan, of samples for IEBAS screening.


Assuntos
3-Hidroxiesteroide Desidrogenases/deficiência , Ácidos e Sais Biliares/urina , Colestase/etiologia , Erros Inatos do Metabolismo/diagnóstico , Oxirredutases/deficiência , Urinálise/métodos , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/complicações , Triagem Neonatal/métodos
16.
Mol Genet Metab ; 127(1): 51-57, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30926434

RESUMO

BACKGROUND: For inborn errors of metabolism (IEM), metabolomics is performed for three main purposes: 1) development of next generation metabolic screening platforms, 2) identification of new biomarkers in predefined patient cohorts and 3) for identification of new IEM. To date, plasma, urine and dried blood spots are used. We anticipate that cerebrospinal fluid (CSF) holds additional - valuable - information, especially for IEM with neurological involvement. To expand metabolomics to CSF, we here tested whether direct-infusion high-resolution mass spectrometry (DI-HRMS) based non-quantitative metabolomics could correctly capture the biochemical profile of patients with an IEM in CSF. METHODS: Eleven patient samples, harboring eight different IEM, and thirty control samples were analyzed using DI-HRMS. First we assessed whether the biochemical profile of the control samples represented the expected profile in CSF. Next, each patient sample was assigned a 'most probable diagnosis' by an investigator blinded for the known diagnoses of the patients. RESULTS: the biochemical profile identified using DI-HRMS in CSF samples resembled the known profile, with - among others - the highest median intensities for mass peaks annotated with glucose, lactic acid, citric acid and glutamine. Subsequent analysis of patient CSF profiles resulted in correct 'most probable diagnoses' for all eleven patients, including non-ketotic hyperglycinaemia, propionic aciduria, purine nucleoside phosphorylase deficiency, argininosuccinic aciduria, tyrosinaemia type I, hyperphenylalaninemia and hypermethioninaemia. CONCLUSION: We here demonstrate that DI-HRMS based non-quantitative metabolomics accurately captures the biochemical profile of this set of patients in CSF, opening new ways for using metabolomics in CSF in the metabolic diagnostic laboratory.


Assuntos
Erros Inatos do Metabolismo/líquido cefalorraquidiano , Erros Inatos do Metabolismo/diagnóstico , Metabolômica/métodos , Biomarcadores/líquido cefalorraquidiano , Humanos , Espectrometria de Massas
17.
J Pediatr Endocrinol Metab ; 32(4): 311-320, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30917104

RESUMO

Most of inborn errors of metabolism (IEMs) and rare endocrine-metabolic diseases (REMD) are rare diseases. According to the European Commission on Public Health, a rare disease is defined, based on its prevalence, as one affecting one in 2000 people. Many IEMs affect body stature, cause craniofacial abnormalities, and disturb the developmental process. Therefore, body proportion, dysmorphic characteristics, and morphological parameters must be assessed and closely monitored. This can be achieved only with the help of an anthropologist who has adequate tools. This is why the role of an anthropologist in collaboration with the physician in the diagnostic process is not to be underestimated. Clinical anthropologists contribute to assessing physical development and improve our understanding of the natural history of rare metabolic diseases. This paper presents anthropometric techniques and methods, such as analysis of demographic data, anthropometric parameters at birth, percentile charts, growth patterns, bioimpedance, somatometric profiles, craniofacial profiles, body proportion indices, and mathematical models of growth curves used in certain rare diseases. Contemporary anthropological methods play an important role in the diagnostic process of rare genetic diseases.


Assuntos
Antropologia/métodos , Erros Inatos do Metabolismo/diagnóstico , Doenças Raras/diagnóstico , Humanos
18.
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
19.
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
20.
J Nerv Ment Dis ; 207(3): 145-151, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30720598

RESUMO

Olfactory reference syndrome (ORS) is a rarely diagnosed psychiatric disorder in which individuals falsely believe that they emit an offensive body odor. This retrospective cohort study characterizes the clinical and demographic features of 54 individuals who presented to a Canadian genetics clinic for query trimethylaminuria (TMAU), an inherited disorder in which a pungent fishy odor is produced. The majority (83%) were found to have a likely diagnosis of ORS and a high rate (73.3%) of concomitant psychiatric disorders; only two patients were diagnosed with TMAU. This study highlights the genetics clinic as an unexpected and major ascertainment point for ORS, and shows that ORS can be differentiated from TMAU by age of onset (~28 years), odor characterization (refuse-related), and the presence of associated comorbid psychiatric diagnoses. There is a low diagnostic rate of ORS, attesting to the need for improved education and awareness.


Assuntos
Delusões/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Percepção Olfatória/fisiologia , Adulto , Transtornos de Ansiedade/epidemiologia , Comorbidade , Delusões/diagnóstico , Delusões/epidemiologia , Feminino , Testes Genéticos , Humanos , Masculino , Erros Inatos do Metabolismo/diagnóstico , Metilaminas/urina , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Estudos Retrospectivos , Transtornos Somatoformes/epidemiologia , Adulto Jovem
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