Hypoadiponectinemia as a marker of increased cardiovascular risk in patients with non-alcoholic fatty liver disease: correlation with albumin/creatinine ratio

ABSTRACT Objective: We assessed plasma adiponectin and its correlation with carotid intima-media-thickness (CIMT), as a marker of atherosclerosis, and urine albumin/creatinine ratio (ACR) in patients with non-alcoholic fatty liver disease (NAFLD). Subjects and methods: The study included 100 Egyptian subjects (50 patients with NAFLD with no history of diabetes or hypertension and 50 age and sex-matched normal healthy control subjects). Urine albumin/creatinine ratio (ACR) was assessed in all participants and fasting plasma adiponectin was measured using ELISA technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using high-resolution Doppler ultrasonography. Results: Mild albuminuria was detected in patients with NAFLD (mean urine ACR = 42 ± 30 mg/g). Plasma adiponectin was significantly lower and urine ACR and CIMT significantly higher in patients with NAFLD as compared with the control group (P < 0.001 for all). A significant negative correlation was found between plasma adiponectin and both urine ACR and CIMT in patients with NAFLD (P < 0.001 and < 0.05 respectively). A significant positive correlation was also found between CIMT and urine ACR in those patients (P < 0.05). Plasma adiponectin and urine ACR were independent determinants of CIMT in patients with NAFLD (P < 0.01 and < 0.05 respectively). Conclusion: Patients with NAFLD, without diabetes, have an increased risk of atherosclerosis and cardiovascular disease. Hypoadiponectinemia and low-grade albuminuria are important markers of that risk.

Metabolic control and body composition of children and adolescents with phenylketonuria / Controle metabólico e composição corporal de crianças e adolescentes com diagnóstico neonatal de fenilcetonúria

ABSTRACT Objective: To characterize metabolic control and verify whether it has any relation with socioeconomic, demographic, and body composition variables in children and adolescents with phenylketonuria (PKU) diagnosed in the neonatal period. Methods: This cohort study collected retrospective data of 53 phenylketonuric children and adolescents. Data on family income, housing, and mother's age and schooling level were collected, and anthropometric measures of body composition and distribution were taken. All dosages of phenylalanine (Phe) from the last five years (2015-2019) were evaluated and classified regarding their adequacy (cutoffs: 0-12 years: 2-6 mg/dL; 12-19 years: 2-10 mg/dL). Adequate metabolic control was considered if ≥7%) of the dosages were within desired ranges. Results: The mean (±standard deviation) age in the last year was 10.1±4.6 years. Most of them were under 12 years old (33/53; 62.3%) and had the classic form of the disease (39/53; 73.6%). Better metabolic control was observed among adolescents (68.4 versus 51.4%; p=0.019). Overweight was found in 9/53 (17%) and higher serum Phe levels (p<0.001) were found in this group of patients. Metabolic control with 70% or more Phe level adequacy decreased along with the arm muscle area (AMA) (ptendency=0.042), being 70.0% among those with low reserve (low AMA), and 18.5% among those with excessive reserve (high AMA). Conclusions: Adequate metabolic control was observed in most patients. The findings suggest that, in this sample, the levels of phenylalanine may be related to changes in body composition.

RESUMO Objetivo: Caracterizar o controle metabólico e verificar se existe relação entre ele, variáveis socioeconômicas, demográficas e composição corporal de crianças e adolescentes com fenilcetonúria (FNC) diagnosticada no período neonatal. Métodos: Coorte com coleta retrospectiva de dados de 53 crianças e adolescentes fenilcetonúricos. Foram coletados dados de renda familiar, moradia, idade e escolaridade materna e realizaram-se medidas antropométricas de composição e distribuição corporal. Todas as dosagens de fenilalanina (Fal) dos últimos cinco anos (2015-2019) foram avaliadas e classificadas quanto à adequação (cortes: 0-12 anos: 2-6 mg/dL; 12-19 anos: 2-10 mg/dL). A proporção de dosagens adequadas ≥70% foi considerada como controle metabólico adequado. Resultados: A média (±desvio padrão) de idade, no último ano, foi de 10,1±4,6 anos. A maioria tinha menos de 12 anos (33/53; 62,3%) e apresentava a forma clássica da doença (39/53; 73,6%). Observou-se melhor controle metabólico entre os adolescentes (68,4 vs. 51,4%; p=0,019). Excesso de peso foi encontrado em 9/53 (17%) e maiores níveis séricos de Fal foram descritos nesse grupo (p<0,001). O percentual de controle metabólico com 70% ou mais de adequação dos níveis de Fal foi decrescente de acordo com a área muscular do braço (AMB; ptendência=0,042), sendo de 70% entre os de baixa reserva (AMB reduzida) e de 18,5% entre os com excesso (AMB elevada). Conclusões: Observou-se controle metabólico adequado na maioria dos avaliados e os achados sugerem que, nesta amostra, os níveis de fenilalanina podem estar relacionados com alterações da composição corporal.

Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients / As deficiências leve e moderada de lectina ligadora de manose estão associadas ao lúpus eritematoso sistêmico e à nefrite lúpica em pacientes brasileiros

Abstract Objective The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Methods Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500 µg/L), moderate (<500 and ≥100 µg/L) or severe (<100 µg/L). Results SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. Conclusion This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis.

Resumo Objetivo Vários estudos já investigaram a potencial associação entre a deficiência de lectina de ligação a manose (LLM) e o lúpus eritematoso sistêmico (LES), mas os resultados obtidos são controversos. Uma explicação para esses resultados conflitantes poderia estar nas diferenças étnicas dos indivíduos estudados. Este estudo investigou a associação entre a deficiência de LLM e o LES em uma grande coorte de pacientes brasileiros com LES e controles. Métodos Determinaram-se os níveis séricos de LLM e complemento em 286 pacientes adultos brasileiros com LES e 301 adultos brasileiros saudáveis que atuaram como controles. A deficiência de LLM foi classificada como leve (< 1000 e ≥ 500 µg/L), moderada (< 500 e ≥ 100 µg/L) ou grave (< 100 µg/L). Resultados Os pacientes com LES apresentaram maior frequência de deficiências leve e moderada de LLM em relação aos controles. Os pacientes com LES com deficiência de LLM apresentaram maior frequência de nefrite lúpica em comparação com aqueles sem deficiência de LLM. A deficiência de LLM não esteve associada a qualquer outra manifestação clínica, uso de terapia imunossupressora, atividade da doença, gravidade da doença ou níveis séricos de complemento. Conclusão Este estudo mostra que há uma associação entre a deficiência de LLM e o LES na população brasileira. Encontrou-se também uma associação entre a deficiência de LLM e a nefrite lúpica. Esses resultados apoiam a hipótese de que a deficiência de LLM contribui para o desenvolvimento do LES e da nefrite lúpica.

Tamizaje neonatal por espectrometría de masas en tándem: actualización / Neonatal screening by tandem mass spectrometry: an update

La espectrometría de masas en tándem (MS/MS) ha posibilitado la expansión de los programas de tamizaje neonatal en diferentes países. Esta tecnología permite el diagnóstico múltiple y rápido de diversos errores innatos del metabolismo. Sin embargo, su aplicación en distintos programas en el ámbito mundial es actualmente muy heterogénea. Existen diferentes criterios para determinar si se incluye una enfermedad específica en esos programas, en algunos casos con un enfoque más restrictivo que en otros, de acuerdo con los principios tradicionales de tamizaje enunciados por Wilson y Jungner, los que habrán de ser reevaluados a la luz de esta nueva tecnología. En este trabajo se presenta una actualización sobre el uso de la MS/MS en diferentes regiones del mundo en relación con las enfermedades tamizadas y con los criterios de inclusión de nuevos problemas de salud en los programas de tamizaje neonatal.

Tandem mass spectrometry (MS/MS) has made it possible to expand neonatal screening programs in different countries. This technology permits multiple and rapid diagnosis of diverse inborn errors of metabolism. However, its use in different programs around the world currently varies widely. There are different criteria for determining whether to include a specific disease in such programs, with some cases employing a more restrictive approach than others, based on the traditional screening principles enunciated by Wilson and Jungner, which will have to be reevaluated in light of this new technology. This article presents an update on the use of MS/MS in different regions of the world in terms of the diseases screened for, and the criteria for including new health problems in neonatal screening programs.

Profile of inborn errors of metabolism in a tertiary care centre PICU.

Objective. To study the clinico-investigative profile and outcome of patients with inborn errors of metabolism (IEM) presenting to the pediatric intensive care unit (PICU). Methods. Records of all patients admitted in tertiary care centre PICU between August 2007 and September 2008 with a diagnosis of IEM were retrieved the details of clinical presentation, laboratory results, treatment and outcome were noted and analysed. Results. Eleven (2.6%) out of 420 PICU admissions during the study period had a diagnosis of IEM with a high mortality rate of 36%. Clinical presentation was quite varied. Conclusion. IEM are not uncommon in PICU. Simple biochemical tests and neuroimaging findings provide vital clues to the diagnosis of IEM.

Enfermedad de orina en jarabe de arce: mejoría clínica asociada a detección precoz y manejo oportuno. Reporte de caso y revisión de literature / Doença de urina em xarope de arce: melhoria clínica relacionada á detecção precoce e manejo oportuno. Reporte de caso e revisão de literatura / Maple syrup urinary disease: clinical improvement associated with early detection and management. Case report and literature review

La enfermedad de orina en jarabe de arce es un error innato del metabolismo de los cetoácidos de cadena ramificada, cuya acumulación produce una encefalopatía neonatal grave y que de no ser diagnosticada y tratada de forma precoz y oportuna, lleva invariablemente a la aparición de secuelas neurológicas permanentes y a un posterior desenlace letal. El presente artículo busca, mediante la descripción de un caso clínico sucedido en el Hospital Militar Central de Bogotá, hacer una revisión de la literatura acerca de la enfermedad, resaltando los mecanismos fisiopatológicos, la detección por diferentes pruebas de laboratorio, así como las estrategias de manejo, demostrando que gracias a los progresos realizados en su comprensión y enfoque, actualmente se puede hablar de evitar la mortalidad, alcanzando en muchos casos, una sobrevida a largo plazo sin mayores secuelas neurológicas, todo ello con un manejo interdisciplinario que logre un control metabólico adecuado...

Maple syrup urine disease is an inborn error of the metabolism of branched chain keto-acids whose accumulation produces a serious neonatal encephalopathy, which if not diagnosed and treated in a precocious and opportune way, will invariably lead to the appearance of permanent neurological impairments and an ulterior lethal outcome. The present article intends, by means of the description of a clinical case which occurred at the Hospital Militar Central, to perform a review of the existent literature on this disease, to revise its fisiopathological mechanisms as well as its detection using different laboratory tests and the different care strategies, to demonstrate that, thanks to the progress achieved in its understanding and focus, at the present moment we can speak of avoiding mortality, accomplishing in many cases long term survival without important neurological consequences, all by means of an interdisciplinary approach that achieves an appropriate metabolic control...

A doença de urina em xarope de arce é um erro inato do metabolismo dos cetoácidos de corrente ramificada, cuja acumulação produz uma encefalopatia neonatal grave e que de não ser diagnosticada e tratada de forma precoce e oportuna, leva invariavelmente à aparição de seqüelas neurológicas permanentes e a um posterior desenlace letal. O presente artigo procura, mediante a descrição de um caso clínico sucedido no Hospital Militar Central de Bogotá, fazer uma revisão da literatura a respeito da doença, ressaltando os mecanismos fisiopatológicos, a detecção por diferentes provas de laboratório, bem como as estratégias de tratamento, demonstrando que graças aos progressos realizados em seu entendimento e enfoque, atualmente se pode falar de evitar a mortalidade, atingindo em muitos casos, uma sobrevida em longo prazo sem maiores seqüelas neurológicas, tudo isso com um manejo interdisciplinares que consiga um controle metabólico adequado...

Burden of genetic disorders in India.

India, like other developing countries, is facing an accelerating demographic switch to non-communicable diseases. In the cities congenital malformations and genetic disorders are important causes of morbidity and mortality. Due to the high birth rate in India a very large number of infants with genetic disorders are born every year almost half a million with malformations and 21,000 with Down syndrome. In a multi-centric study on the causes of referral for genetic counselling the top four disorders were repeated abortions (12.4%), identifiable syndromes (12.1%), chromosomal disorders (11.3%) and mental retardation (11%). In a more recent study in a private hospital the top reasons for referral were reproductive genetics (38.9%)--comprising prenatal diagnosis, recurrent abortions, infertility and Torch infections--mental retardation +/- multiple congenital anomalies (16.1%), Down syndrome (9.1%), thalassemia/haemophilia (8.8%), and muscle dystrophy/spinal muscular atrophy (8.4%). The disorders for which prenatal has been done over an 18-month-period are given. A recent study carried out in three centers (Mumbai, Delhi and Baroda) on 94,610 newborns by using a uniform proforma showed a malformation frequency of 2.03%, the commonest malformations are neural tube defects and musculo-skeletal disorders. The frequency of Down syndrome among 94,610 births was 0.87 per 1000, or 1 per 1150. Screening of 112,269 newborns for aminoacid disorders showed four disorders to be the commonest--tyrosinemia, maple syrup urine disease and phenylketonuria. Screening of cases of mental retardation for aminoacid disorders revealed four to be the commonest--hyperglycinemia, homocystinuria, alkaptonuria, and maple syrup urine disease. Metabolic studies of cases of mental retardation in AIIMS, Delhi and KEM Hospital, Mumbai, demonstrated that common disorders were those of mucopolysaccharides, lysosomes, Wilson disease, glycogen storage disease and galactosemia. It is estimated that beta- thalassemia has a frequency at birth of 1:2700, which means that about 9,000 cases of thalassemia major are born every year. Almost 5200 infants with sickle cell disease are born every year. Disorders, which deserve to be screened in the newborn period, are hypothyroidism and G-6-PD deficiency, while screening for aminoacid and other metabolic disorders could presently be restricted to symptomatic infants.

new experience with the diagnosis of inborn metabolic diseases in Bahrain

Since the Section of metabolic diseases has been established in the Department of Paediatrics, Salmaniya Medical Complex, Bahrain in October 1997, 176 patients were referred to it suspected of having a metabolic disorder, out of which 23 patients with various errors of metabolism have been identified in 10 months period. These data are found to be of a higher frequency [1/470 annual births] than a neighbouring country sharing common cultural and social background [Saudi Arabia] [1/815 annual births]. It has been suggested that the incidence of organic acid disorders [OAD] in the world is approximately 1/10,000 births, while in the Arabian peninsula the incidence of OAD is estimated to be 12-times higher than the world figure. Undoubtedly, the increased incidence of these diseases in Bahrain might partly be due to the availability of a diagnostic service and partly due to the high level of consanguinity. In the past, many such cases did not survive. Nowadays the inherited metabolic disorders have become a universal problem. Through the help of early recognition of such diseases [including prenatal diagnosis and newborn screening program], advances in the diagnostic, and availability of appropriate therapy and genetic counseling, the management and outcome of these diseases have also improved significantly. Indeed most of these patients are now living a better quality of life which otherwise would have lifelong crippling consequences

Glutathione reductase deficiency in Saudi Arabia

Glutathione reductase [GR] is a ubiquitous enzyme required for the conversion of oxidized glutathione [GSSG] to reduced glutathione [GSH] concomitantly oxidizing reduced nicotinamide adenine dinucleotide phosphate [NADPH] in a reaction essential for the stability and integrity of red cells. Mutations in the GR gene and nutritional deficiency of riboflavin, a co-factor required for the normal functioning of GR, can cause GR deficiency. We conducted a study on 1691 Saudi individuals to determine the overall frequency of GR deficiency and to identify whether the deficiency results from genetic or acquired causes or both. The activity of GR was measured in freshly prepared red cell haemolysate in the presence and absence of flavin adenine dinucleotide [FAD] and the activity coefficient [AC] was determined. Samples with low GR activity [> 2.0 IU/g haemoglobin] both in the presence and absence of FAD and an AC between 0.9 and 1.2 were considered GR-deficient. Samples with AC >/= 1.3 were considered riboflavin-deficient. The overall frequency of partial GR deficiency was 24.5% and 20.3% in males and females respectively. In addition, 17.8% of males and 22.4% of females suffered from GR deficiency due to riboflavin deficiency. This could be easily corrected by dietary supplementation with riboflavin. No cases of severe GR deficiency were identified

Los errores innatos del metabolismo en Colombia

EL presente trabajo estuvo dirigido a anlizar el avance en el campo de los errores innatos del metabolismo, tanto en el diagnóstico por el laboratorio como en el conocimiento de estas enfermedades en Colombia. Se analizo la forma como se remiten los pacientes, la procedencia de los mismos, la especialidad de los medicos remitentes, la impresion diagnostica y el diagnostico final. Los estudios del laboratorio se enfocaron tomando como base el diagnostico presuntivo, luego se aplicaron baterias de tipo general para carbohidratos, aminoacidopatias, acidurias organicas o para desordenes neurodegenerativos y se fue profundizando hasta llegar al analisis de la enzima o proteina que define el diagnostico. Para tres enfermedades hemos llegado al nivel de DNA. Hace 5 años publicamos los hallazgos efectuados en este campo en la población colombiana. La comparación entre los dos estudios permite evaluar ele avance logrado especialmente con la introduccion de la cromatografia de gas acoplada a la espectometria de masas, para el diagnostico de las acidemias organicas, de nuevas tecnicas enzimaticas para el diagnostico de mucopolisacaridosis y enfermedades neurodegenerativas. Las acidurias glutarica tipo I, tipo II, la piroglutamica y la 3 OH, 3 metilglutarica son los primeros casos que se reportan en Colombia. El porcentaje de pacientes remitidos sin impresion diagnostica o con solicitud de estudio metabolico no definido, bajo del 75 porciento al 25 porciento; lo anterior permite concluir que hemos hecho notables avances diagnosticos y por laboratorio de los EIM en Colombia

Medical genetics in Japan.

In Japan genetic diseases are getting more popular in medicine, because of increased awareness of the role of genetic determinants of diseases. Care for patients with inherited disease is one of the current big problems. In this review, programs developed to support Duchenne muscular dystrophy patients are described as an example of medical services available for genetic diseases in Japan.

Multicentric study on genetic causes of mental retardation in India. ICMR Collaborating Centres & Central Co-ordinating Unit.

A study on 1314 children with mental retardation (MR) without an obvious environmental cause was carried out at Bangalore, Bombay, Delhi and Lucknow to determine the extent and pattern of genetic causes of mental retardation in different parts of India. In all, 42.3 per cent patients had mild, 25.3 per cent moderate, 19.2 per cent severe and 13.1 per cent profound mental retardation. Among 1314 patients, the chromosomal anomalies were found in 23.7 per cent, metabolic defects in 5.0 per cent and an identificable genetic syndrome in 11.6 per cent of the patients. In the remaining 59.7 per cent patients, no known genetic cause could be identified. However, 66.5 per cent of these patients had one or more of the following conditions: (i) congenital malformation with or without neurological deficit, (ii) history of consanguinity, (iii) positive family history of mental retardation or (iv) a positive screening test but without a confirmed diagnosis of metabolic defect (suggesting that there may be additional unidentified genetic causes of mental retardation).

Detecçäo de distúrbios metabólicos em deficientes mentais em Salvador - Ba / Detection of metabolic disorders in institutionalized mentally deficent patients in Salvador, Bahia

O presente estudo teve como objetivo determinar a freqüência de distúrbios metabólicos em deficientes mentais institucionalizados em Salvador-BA e em pacientes atendidos no Laboratório de Genética Médica do HIPES no ano de 1989. No 1§ grupo de pacientes, foram selecionados 297 indivíduos com deficiência mental moderada, ou grave, ou profunda sem diagnóstico etiológico estabelecido. Destes, 258 indivíduos foram submetidos à avaliaçäo laboratorial para detecçäo de distúrbios metabólicos, por intermédio da realizaçäo de uma bateria de técnicas de triagem. No 2§ grupo foram atendidos no Laboratório de Genética do HUPES 65 pacientes, encaminhados para investigaçäo de erro inato do metabolismo (EIM), apresentando sinais ou sintomas que sugerissem a suspeita diagnóstica de EIM. Em todos foram realizadas técnicas de triagem. Os indivíduos que apresentaram alteraçöes nas técnicas de triagem foram submetidos à avaliaçäo diagnóstica. No primeiro grupo, distúrbios metabólicos foram detectados em 1,55// dos deficientes, näo sendo possível estabelecer o diagnóstico final em nenhum deles. No segundo grupo, 8 pacientes (12,31//) apresentaram alteraçöes nas técnicas de triagem. Estes e mais 22 pacientes com triagem normal, mas com quadro clínico sugestivo de EIM näo detectável pelas técncias de triagem, foram selecionados para investigaçäo diagnóstica. Distúrbios metabólicos foram detectados em 12 pacientes (18,46// do total), porém em apenas 6 pacientes um diagnóstico específico de EIM foi estabelecido, correspondendo a uma freqüência de 9,23// do total de pacientes

Detection of inborn errors of metabolism in patients of pediatric intensive care units of Porto Alegre, Brazil: comparison of the prevelance of such disturbances in a selected and an unselected sample

Foi realizado um estudo de erros inatos do metabolismo (IEM) em crianças hospitalizadas em unidades de tratamento intensivo pediátricas de Porto Alegre, Brasil. Foram avaliadas clínica e laboratorialmente 232 crianças näo selecionadas e 59 selecionadas clinicamente através de sintomas e sinais sugestivos de EIM. Foram empregados testes urinários de triagem, cromatografia e eletroforese em papel de aminoácidos em sangue e urina, cromatografia de glicídios urinários em camada delgada e quantificaçäo de aminoácidos por analisador e de ácidos orgânicos por cromatografia gasosa e espectrometria de massa quando necessário. A freqüência de EIM encontrada nos pacientes selecionados (1:15) foi significativamente maior (<0.05) do que a encontrada nos näo selecionados (1.232). Esta diferença é explicada, em parte, pela alta incidência de infecçöes, prematuridade e desnutriçäo no grupo de pacientes näo selecionados. Os achados clínicos mais encontrados nos pacientes com EIM foram acidose, convulsöes e disfunçäo hepática. Os resultados sugerem que a pesquisa de EIM em crianças severamente doentes em paises em desenvolvimento deve ser restrita àquelas selecionadas clinicamente por sintomas e sinais sugestivos destas doenças. Na amostra näo selecionada foi encontrado um paciente com acidúria metilmalônica; na amostra selecionada, foram detectados pacientes com acidose lática, acidose tubular renal proximal primária, hiperprolinemia tipo II e tirosinemia tipo I. Devido à sua alta incidência, as acidúrias o