Disease progression in Sanfilippo type B: Case series of Brazilian patients.

Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.

The fructose-1,6-bisphosphatase deficiency and the p.(Lys204ArgfsTer72) variant.

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inborn error of fructose metabolism caused by pathogenic variants in the FBP1 gene. As gluconeogenesis is affected, catabolic episodes can induce ketotic hypoglycemia in patients. FBP1 analysis is the most commonly used approach for the diagnosis of this disorder. Herein, a Brazilian patient is reported. The proband, a girl born to a consanguineous couple, presented with severe hypoglycemia crisis in the neonatal period. At the age 17 months, presented a new crisis accompanied by metabolic acidosis associated with a feverish episode. Genetic analysis was performed by next-generation sequencing (NGS), identifying the NM_000507.3:c.611_614del variant in homozygosis in the FBP1 gene. In silico analysis and 3D modeling were performed, suggesting that this variant is associated with a loss of sites for substrate and Mg2+ binding and for posttranslational modifications of FBPase. The c.611_614del variant is located in a repetitive region of the FBP1 gene that appears to be a hotspot for mutational events. This frameshift creates a premature termination codon in the last coding exon which escapes the nonsense-mediated decay mechanism, according to in silico analysis. This variant results in an intrinsically disordered protein with loss of substrate recognition and post-translational modification sites.

Lysosomal diseases: Overview on current diagnosis and treatment.

Lysosomal diseases (LDs), also known as lysosomal storage diseases (LSDs), are a heterogeneous group of conditions caused by defects in lysosomal function. LDs may result from deficiency of lysosomal hydrolases, membrane-associated transporters or other non-enzymatic proteins. Interest in the LD field is growing each year, as more conditions are, or will soon be treatable. In this article, we review the diagnosis of LDs, from clinical suspicion and screening tests to the identification of enzyme or protein deficiencies and molecular genetic diagnosis. We also cover the treatment approaches that are currently available or in development, including hematopoietic stem cell transplantation, enzyme replacement therapy, small molecules, and gene therapy.

Information and Diagnosis Networks - tools to improve diagnosis and treatment for patients with rare genetic diseases.

Brazil is a country of continental dimensions and most genetic services are concentrated in the Southeast and South, including the Medical Genetics Service of the Hospital de Clínicas de Porto Alegre (MGS/HCPA). As many areas on the country do not have adequate medical genetics support, networks were designed to extend the service of the MGS/HCPA reference center. This paper presents the information and diagnosis networks that have their headquarters at MGS/HCPA: SIAT (National Information System on Teratogenic Agents), SIEM (Information Service on Inborn Errors of Metabolism), Alô Genética (Hello Genetics - Medical Genetics Information Service for Primary Health Care Professionals); Rede MPS Brasil (MPS-Mucopolysaccharidosis Brazil Network); Rede EIM Brasil (IEM-Inborn Errors of Metabolism Brazil Network), Rede NPC Brasil (Niemann-Pick C - NPC Brazil Network), Rede DLD Brasil (LSD-Lysosomal Storage Disorders Brazil Network), Rede DXB (MSUD-Maple Syrup Urine Disease Network), RedeBRIM (Brazilian Network of Reference and Information in Microdeletion Syndromes Project), Rede Neurogenética (Neurogenetics Network), and Rede Brasileira de Câncer Hereditário (Brazilian Hereditary Cancer Network). These tools are very useful to provide access to a qualified information and/or diagnostic service for specialized and non-specialized health services, bypassing difficulties that preclude patients to access reference centers.

Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center.

OBJECTIVES: To characterize cases of suspected congenital disorders of glycosylation (CDG) investigated in a laboratory in southern Brazil using the transferrin isoelectric focusing TfIEF test from 2008 to 2017. METHOD: Observational, cross-sectional, retrospective study. The laboratory records of 1,546 individuals (median age=36 months, 25-75 IQR=10-108; males=810) submitted to the TfIEF test during the period were reviewed. RESULTS: Fifty-one individuals (3%) had an altered TfIEF pattern (5±2.8 cases/year; median age=24 months, 25-75 IQR=11-57 months; males=27, 53%). For 14 of them, data on diagnosis conclusion were available (classic galactosemia=4; hereditary fructose intolerance=4; peroxisomal diseases=2; PMM2-CDG=2; MPDU1-CDG=1; SLC35A2-CDG=1).Comparing the cases with the normal and altered TfIEF patterns, there was a higher prevalence of altered cases in the age group from 11 months to 3 years. There was an increase in the likelihood of change in TfIEF, especially in the presence of inverted nipples or liver disease. CONCLUSIONS: The data suggest that the investigation of a case with suspected CDG is a complex problem, being aggravated by the existence of other IEMs (inborn errors of metabolism) associated with altered TfIEF pattern and lack of access to confirmatory tests. The presence of inverted nipples and liver disease, especially in individuals aged 11 months to 3 years, should suggest the need for TfIEF investigation.

A Retrospective Study of Mucopolysaccharidosis Type II in Brazil - Data from Brazilian Health System (DATASUS)

Abstract Data on Mucopolysaccharidosis type II (MPS II) in Latin America are scarce. This retrospective database study, using data from the Informatics Department of the Brazilian Health System (DATASUS), aimed to estimate the prevalence of MPSII in Brazil from 2008 to 2020 and to describe demographic and clinical profiles from patients under treatment. The study population was derived from DATASUS records of MPS II (ICD-10 E76.1) diagnosed in Brazil. Initially 455 patients were found, but only 181 patients who were receiving idursulfase treatment were included in this study. Among these cases, as expected in a X-linked disease, all were males and 40% of the cases were recorded in the Southeast region, and another 34% in the Northeast region. The biggest proportion of patients (39%) were diagnosed when they were 10-19 years old. There are 212 clinical conditions associated with MPS II, although the main comorbidities related to MPSII include: abdominal/inguinal hernia, respiratory complications, and carpal tunnel syndrome. Respiratory disorders were the fifth most frequent comorbidity recorded in these patients. The healthcare professionals in Brazil more involved in the diagnosis of MPS II were radiologists, followed by geneticists and cardiologists. Despite some limitations, DATASUS is a relevant database to provide information on rare diseases such as MPS II. Most cases were reported in southeast and northeast regions, respectively. This information is crucial to help design targeted public policies.

[Psychotic syndrome developing into dementia as a clinical manifestation of mitochondrial DNA deletion]. / Síndrome psicótica evoluindo com demência como manifestação clinica de deleção do DNA mitocondrial.

The manifestations of mitochondrial disease are variable, affecting more frequently the organs with high aerobic metabolism in which they are more abundant, for example the nervous system. The beginning of symptoms in general is observed at childhood, but some patients presented on adult age. We present an atypical case associated with mitochondrial DNA deletion. A 39-years-old man with psychiatric symptoms that configured initial clinical picture and only after 12 years of the beginning of symptoms neurological alterations became noticeable. The diagnosis of mitochondrial illness was confirmed by muscle biopsy being documented mitochondrial DNA deletion.

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome.

OBJECTIVE: To describe survival and neurological outcomes after HSCT for these disorders. METHODS: Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. RESULTS: Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. CONCLUSION: Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

Maple syrup urine disease in Brazil: a panorama of the last two decades.

OBJECTIVE: To characterize a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011. METHODS: In this retrospective study, patients were identified through a national reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. Data were collected by means of a chart review. RESULTS: Eighty-three patients from 75 families were enrolled in the study (median age, 3 years; interquartile range [IQR], 0.57-7). Median age at onset of symptoms was 10 days (IQR 5-30), whereas median age at diagnosis was 60 days (IQR 29-240, p=0.001). Only three (3.6%) patients were diagnosed before the onset of clinical manifestations. A comparison between patients with (n=12) and without (n=71) an early diagnosis shows that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. Overall, 98.8% of patients have some psychomotor or neurodevelopmental delay. CONCLUSION: In Brazil, patients with MSUD are usually diagnosed late and exhibit neurological involvement and poor survival even with early diagnosis. We suggest that specific public policies for diagnosis and treatment of MSUD should be developed and implemented in the country.

Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center / Isoeletrofocalização da transferrina para investigação das doenças congênitasda glicosilação: análise de dez anos de experiência de um centro brasileiro

Abstract Objectives: To characterize cases of suspected congenital disorders of glycosylation (CDG) investigated in a laboratory in southern Brazil using the transferrin isoelectric focusing TfIEF test from 2008 to 2017. Method: Observational, cross-sectional, retrospective study. The laboratory records of 1,546 individuals (median age = 36 months, 25-75 IQR = 10-108; males = 810) submitted to the TfIEF test during the period were reviewed. Results: Fifty-one individuals (3%) had an altered TfIEF pattern (5 ± 2.8 cases/year; median age = 24 months, 25-75 IQR = 11-57 months; males = 27, 53%). For 14 of them, data on diagnosis conclusion were available (classic galactosemia = 4; hereditary fructose intolerance = 4; peroxisomal diseases = 2; PMM2-CDG = 2; MPDU1-CDG = 1; SLC35A2-CDG = 1).Comparing the cases with the normal and altered TfIEF patterns, there was a higher prevalence of altered cases in the age group from 11 months to 3 years. There was an increase in the likelihood of change in TfIEF, especially in the presence of inverted nipples or liver disease. Conclusions: The data suggest that the investigation of a case with suspected CDG is a complex problem, being aggravated by the existence of other IEMs (inborn errors of metabolism) associated with altered TfIEF pattern and lack of access to confirmatory tests. The presence of inverted nipples and liver disease, especially in individuals aged 11 months to 3 years, should suggest the need for TfIEF investigation.

Resumo Objetivos: Caracterizar os casos com suspeita de CDG investigados em laboratório do sul do Brasil pelo exame de IEFTF de 2008 a 2017. Metodologia: Estudo observacional, transversal, retrospectivo. Foram revisadas as fichas laboratoriais de 1.546 indivíduos (mediana de idade = 36 meses, IQ 25-75 = 10-108; sexo masculino = 810) que fizeram o exame de IEFTF no período. Resultados: Cinquenta e um indivíduos (3%) apresentaram padrão alterado na IEFTF (5 ± 2,8 casos/ano; mediana de idade = 24 meses, IQ 25-75 = 11-57 meses; sexo masculino = 27, 53%). Para 14 deles, estavam disponíveis dados sobre a conclusão do diagnóstico (galactosemia clássica = 4; intolerância hereditária à frutose = 4; doenças peroxissomais = 2; PMM2-CDG = 2; MPDU1-CDG = 1; SLC35A2-CDG = 1). Comparando os casos com padrão normal e alterado na IEFTF, houve maior prevalência de casos alterados na faixa etária de 11 meses a 3 anos. Verificou-se um aumento na probabilidade de alteração na IEFTF principalmente na presença de mamilos invertidos ou de hepatopatia. Conclusões: Os nossos dados sugerem que a investigação de um caso com suspeita de CDG é complexa, é agravada pela existência de outros EIM associados a padrão alterado na IEFTF e pela falta de acesso a exames confirmatórios. A presença principalmente de mamilos invertidos e de hepatopatia em indivíduos na faixa etária de 11 meses a 3 anos deve sugerir a necessidade de investigação por IEFTF.

Análise da densidade mineral óssea em pacientes com fenilcetonúria e sua correlação com parâmetros nutricionais / Bone mineral density assessment in patients with phenylketonuria and its correlation with nutritional parameters

Introdução: Redução da densidade mineral óssea (DMO) está associada à Fenilcetonúria (PKU), mas a causa desta associação não é completamente entendida. O objetivo desse estudo foi avaliar a ingestão de nutrientes relacionados ao metabolismo ósseo (cálcio, fósforo, magnésio, potássio), e sua associação com a DMO em pacientes com PKU. Métodos: Estudo transversal, observacional. Foram incluídos 15 pacientes (PKU Clássica=8; Leve=7; mediana de idade=16 anos, IQ=15-20), todos em tratamento com dieta restrita em fenilalanina (Phe) e 13 em uso de fórmula metabólica. Foi realizado recordatório alimentar de 24 horas de um dia e demais dados (histórico de fraturas, parâmetros antropométricos, DMO e níveis plasmáticos de Phe, Tyr, cálcio) foram obtidos por revisão de prontuário. Resultados: Nenhum paciente apresentou histórico de fraturas e seis realizavam suplementação de cálcio (alteração prévia da DMO=5; baixa ingestão=1). A mediana dos níveis de Phe foi 11,6 mg/dL (IQ=9,3-13,3). Em relação ao recordatório alimentar, dez indivíduos apresentaram inadequado consumo de carboidratos; 14, de lipídeos; 9, de cálcio; 11, de magnésio; 13, de fósforo; e todos de potássio. A mediana da DMO foi de 0,989 g/cm2 (IQ=0,903-1,069), sendo duas classificadas como reduzidas para idade, ambas de pacientes com PKU Leve que recebiam suplementação de cálcio. Não foi observada correlação entre níveis de Phe, DMO e demais variáveis analisadas. Conclusão: Redução da DMO não foi frequente na amostra, embora ingestão inadequada de cálcio assim o seja. Estudos adicionais são necessários para esclarecer o efeito da Phe e da ingestão dietética sobre o metabolismo ósseo na PKU. (AU)

Introduction: Reduced bone mineral density (BMD) is associated with phenylketonuria (PKU), but this association is not completely understood. This research aimed to evaluate intake of nutrients related to bone metabolism (calcium, phosphorus, magnesium, potassium) and its association with BMD in patients with PKU. Methods: In this cross-sectional, observational study, 15 patients with PKU (Classical=8, Mild=7; median age=16 years, IQ=15-20 years) were included, all of them on phenylalanine (Phe) restricted diet and 13 being supplemented with a metabolic formula. A 24-hour dietary recall was performed and remaining data (history of fractures, anthropometric parameters, BMD and plasma Phe, tyrosine and calcium levels) were obtained through medical chart review. Results: No patient had any fractures and six received calcium supplements, five due to previous change in BMD and one due to inadequate nutritional intake. Median Phe level was 11.6 mg/dL (IQ=9.3-13.3). In relation to dietary recall, all individuals had inadequate intake of some nutrient (carbohydrate=10; lipids=14; calcium=9; magnesium=11; phosphorus=13; potassium=15). The median BMD was 0.989 g/cm2 (IQ=0.903-1.069). Two cases were classified as low BMD for age, both in patients with mild PKU receiving calcium supplements. Conclusion: Reduced BMD was not common in this sample, although inadequate calcium intake was frequently reported. Additional studies are needed to clarify the effect of Phe and dietary intake on bone metabolism in patients with PKU.(AU)

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome / Desfechos neurológicos após transplante de células tronco hematopoiéticas na adrenoleucodistrofia ligada ao X, forma cerebral, na leucodistrofia metacromática de início tardio e na síndrome de Hurler

ABSTRACT Hematopoietic stem cell transplantation (HSCT) is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I-Hurler (MPS-IH), and X-linked cerebral adrenoleukodystrophy (CALD). Objective To describe survival and neurological outcomes after HSCT for these disorders. Methods Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Results Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Conclusion Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

RESUMO O transplante de células tronco hematopoiéticas (TCTH) é o único tratamento disponível para o envolvimento neurológico de doenças como a leucodistrofia metacromática (MLD), a mucopolissacaridose tipo I-Hurler (MPS-IH) e a adrenoleucodistrofia (CALD). Objetivos Descrever a sobrevida e os desfechos neurológicos após o TCTH nessas doenças. Métodos Sete pacientes CALD, 2 MLD e 2 MPS-IH realizaram TCTH entre 2007 e 2014. Avaliações neurológicas, ressonância nuclear magnética e estudos bioquímicos e moleculares foram feitos no baseline e repetidos quando apropriado. Resultados Desfechos favoráveis foram obtidos em 4/5 TCTH de doadores relacionados e em 3/6 não relacionados. Dois pacientes faleceram de complicações do procedimento. Nove transplantados sobreviveram após uma mediana de 3,7 anos: estabilização neurológica foi obtida em 5/6 CALD, ½ MLD e em um caso MPS-IH. As lesões encefálicas de um caso MPS-IH reduziram-se quatro anos após o TCTH. Conclusão Bons desfechos foram obtidos quando o TCTH foi feito antes da vida adulta, cedo no curso clínico e/ou a partir de um doador relacionado.

Alternative laronidase dose regimen for patients with mucopolysaccharidosis I: a multinational, retrospective, chart review case series

A terapia de reposição enzimática (TRE) com laronidase (α-L-iduronidase humana recombinante, Aldurazyme®) é indicada para sinais e sintomas não neurológicos da mucopolissacaridose tipo I (MPS I). O regime de dose de laronidase aprovado é de infusões semanais de 0,58mg / kg; no entanto, pacientes e cuidadores podem ter dificuldade em cumprir o regime semanal. Examinamos os resultados clínicos, tolerabilidade, adesão e satisfação em uma série de pacientes que mudavam para infusões a cada duas semanas. Métodos: Esta série de casos multinacionais, retrospectiva, de revisão de prontuários analisou dados de 20 pacientes submetidos à ERT com laronidase 0,58mg / kg semanalmente por mais de um ano e que passaram a 1,2mg / kg a cada duas semanas. Resultados: A maioria dos pacientes apresentou fenótipos de MPS I atenuados (9 com síndrome de Hurler-Scheie e 8 com síndromes de Scheie) e 3 pacientes apresentaram MPS I grave (síndrome de Hurler). A maioria dos pacientes apresentou organomegalia (17/20), hérnia umbilical e / ou inguinal (16/20), anormalidades cardíacas (17/20), anormalidades musculoesqueléticas (19/20) e déficits neurológicos e / ou de desenvolvimento (15/20 ) Após o tratamento com laronidase, os sinais estabilizaram ou melhoraram. Não foi observada deterioração ou reversão do resultado clínico em nenhum paciente que passou da dose semanal de 0,58 mg.kg para 1,2 mg / kg a cada duas semanas. Não houve problemas de segurança durante a duração da administração em semanas alternadas. A adesão do paciente e a satisfação com o regime posológico foram maiores a cada duas semanas do que a dose semanal. Conclusões: Um regime de dose alternativo de 1,2 mg / kg de laronidase a cada duas semanas foi bem tolerado e clinicamente semelhante à dose padrão para pacientes que foram estabilizados com 0,58 mg / kg semanalmente por um ano ou mais. Quando é necessária uma abordagem individualizada da terapia com laronidase, a administração em semanas alternadas pode ser uma alternativa para pacientes com dificuldade em receber infusões semanais.

Maple syrup urine disease in Brazil: a panorama of the last two decades / Doença da urina de xarope de bordo no Brasil: um panorama das últimas duas décadas

OBJECTIVE: To characterize a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011. METHODS: In this retrospective study, patients were identified through a national reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. Data were collected by means of a chart review. RESULTS: Eighty-three patients from 75 families were enrolled in the study (median age, 3 years; interquartile range [IQR], 0.57-7). Median age at onset of symptoms was 10 days (IQR 5-30), whereas median age at diagnosis was 60 days (IQR 29-240, p = 0.001). Only three (3.6%) patients were diagnosed before the onset of clinical manifestations. A comparison between patients with (n = 12) and without (n = 71) an early diagnosis shows that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. Overall, 98.8% of patients have some psychomotor or neurodevelopmental delay. CONCLUSION: In Brazil, patients with MSUD are usually diagnosed late and exhibit neurological involvement and poor survival even with early diagnosis. We suggest that specific public policies for diagnosis and treatment of MSUD should be developed and implemented in the country. .

OBJETIVO: Caracterizar uma amostra de pacientes brasileiros com a doença da urina de xarope de bordo (DXB) diagnosticados entre 1992 e 2011. MÉTODOS: Os pacientes foram identificados por meio de um laboratório de referência nacional para o diagnóstico de DXB e por meio do contato com outros serviços de genética médica no Brasil. Os dados foram coletados por meio de uma revisão de prontuários. RESULTADOS: Foram incluídos no estudo 83 pacientes de 75 famílias (idade média: três anos; intervalo interquartil (IQR): 0,57-7). A idade média no surgimento dos sintomas era de 10 dias (IQR: 5-30), ao passo que a idade média no diagnóstico era de 60 dias (IQR: 29-240; p = 0,001). Somente três (3,6%) pacientes foram diagnosticados antes do surgimento de manifestações clínicas. Uma comparação entre pacientes com (n = 12) e sem (n = 71) um diagnóstico precoce mostra que o diagnóstico precoce está associado à presença de histórico familiar positivo e à redução na prevalência de manifestações clínicas no momento do diagnóstico, porém sem melhor resultado. Em geral, 98,8% dos pacientes têm algum atraso no desenvolvimento psicomotor ou neurológico. CONCLUSÃO: No Brasil, os pacientes com DXB normalmente recebem um diagnóstico tardio e exibem um envolvimento neurológico e baixa sobrevivência, mesmo com um diagnóstico precoce. Sugerimos que políticas públicas específicas para o diagnóstico e tratamento da DXB sejam desenvolvidas e implementadas no país. .

Treatment of inborn errors of metabolism.

OBJECTIVE: To describe the current state of treatment for disorders of intermediate metabolism (primarily of amino acids, urea cycle and organic acids) and for diseases related to two subcellular organelles (lysosomes and peroxisomes). SOURCES: In covering the treatment of disorders of intermediate metabolism, priority was given to the most important methods for managing intoxication, in view of the importance for pediatricians to treat acute and life-threatening cases. The article also provides a general overview of the treatment for lysosomal and peroxisomal diseases, with emphasis on enzyme replacement therapy, which is a treatment modality that is growing in use and with which pediatricians should make themselves familiar. SUMMARY OF THE FINDINGS: The most important measures used to manage the intoxication present in many inborn errors of intermediate metabolism were presented (restriction of substrate build-up by means of diet or enzymatic inhibition, removal of toxic products, stimulation of residual enzyme activity, replacement of the deficient product). The section on treatment for lysosomal and peroxisomal diseases includes tables providing information on the treatments available. CONCLUSIONS: Treating inborn errors of metabolism is a complex task that should be performed by a multidisciplinary team of which the pediatrician is the key member. This article provides practical information relating to the management of some inborn errors of metabolism and provides pediatricians with a general overview of recent developments in this area of medicine.

Polymerase chain reaction as a useful and simple tool for rapid diagnosis of tuberculous meningitis in a Brazilian tertiary care hospital.

Meningitis is a severe and potentially fatal form of tuberculosis. The diagnostic workup involves detection of acid-fast bacilli (AFB) in the cerebrospinal fluid (CSF) by microscopy or culture, however, the difficulty in detecting the organism poses a challenge to diagnosis. The use of the polymerase chain reaction (PCR) in the diagnostic approach to Mycobacterium tuberculosis (MTB) meningitis has been reported as a fast and accurate method, with several commercial kits available. As an alternative, some institutions have been developing inexpensive in house assays. In our institution, we use an in house PCR for tuberculosis. We analyzed the performance of our PCR for the diagnosis of MTB meningitis in 148 consecutive patients, using MTB culture as gold standard. The sensitivity and specificity of CSF PCR for the diagnosis of MTB meningitis was 50% and 98.6% respectively with a concordance with CSF mycobacterial culture of 96% (Kappa=0.52). In contrast to CSF cultures for MTB, our PCR test is a fast, simple and inexpensive tool to diagnose tuberculous meningitis with a performance similar to that obtained with the available commercial kits.