RESUMO
BACKGROUND: Lipid metabolism is considerably complex and there can be many critical steps in atherogenesis. The association between lysosomal acid lipase (LAL) activity and coronary artery disease (CAD) has not been elucidated in detail. We aimed to evaluate the association between LAL activity with the presence and severity of CAD in patients who are seen in daily clinical practice. METHODS: Patients who underwent coronary angiography were divided into groups according to the angiography results. Syntax scores and Gensini scores were calculated. The LAL activity was measured from dried blood spots. RESULTS: Median LAL activity values were similar in all study groups (normal coronary arteries: 0.40â¯nmol/punch/h; non-obstructive CAD: 0.44â¯nmol/punch/h; obstructive chronic CAD: 0.40â¯nmol/punch/h; obstructive acute coronary syndrome: 0.48â¯nmol/punch/h) and there was no correlation between coronary atherosclerotic burden and LAL activity (correlation coefficients Syntax score and LAL: -0.032; Gensini score and LAL: -0.030). In addition, no relationship between serum lipid levels and LAL activity was detected. CONCLUSION: The presence of CAD and its severity is not associated with the LAL activity in patients encountered in daily clinical practice.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Esterol Esterase , Angiografia Coronária , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND OBJECTIVE: Pompe disease (PD) is an inherited lysosomal storage disease that progresses with glycogen accumulation in many tissues, due to the deficiency of the acid-alpha glucosidase enzyme. Recombinant alglucosidase alfa (rhGAA) is the only disease-specific treatment option, in the form of enzyme replacement therapy (ERT). Anaphylaxis can develop with rhGAA. There is no study evaluating anaphylaxis and its management in PD in the long term. We aimed to evaluate the development of anaphylaxis and rapid drug desensitization (RDD) with rhGAA in children with PD. MATERIALS AND METHODS: All children diagnosed and followed up in our institution with PD over 12 years between January 2009 and September 2021 were evaluated for development of anaphylaxis and RDD with rhGAA from medical records. RESULTS: Fourteen patients, 64% of whom were female and diagnosed with PD (1 juvenile, 13 infantile types) during the study period included in the study. The median age at diagnosis was 3.2 months (1-40 months). The median follow-up time of the patients was 20 months (1-129 months). Thirteen patients were given rhGAA, one died before ERT. Four (30.8%) patients developed moderate to severe anaphylaxis, and RDD was applied with rhGAA. A total of 390 RDDs have been performed so far without any serious breakthrough reactions during all RDDs. CONCLUSIONS: Anaphylaxis with rhGAA is not rare and RDD with rhGAA is safe and effective in the long term.
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Anafilaxia , Doença de Depósito de Glicogênio Tipo II , Criança , Humanos , Feminino , Lactente , Masculino , alfa-Glucosidases/uso terapêutico , Doença de Depósito de Glicogênio Tipo II/complicações , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Anafilaxia/terapia , Anafilaxia/tratamento farmacológico , Terapia de Reposição de EnzimasRESUMO
BACKGROUND/AIM: There have been no studies to date examining the effect of metformin treatment on vitamin B12 status in children and adolescents. In this prospective study, the effects of metformin on blood vitamin B12, serum methylmalonic acid (MMA), homocysteine and holo-transcobalamin-II (holo-TC-II) levels were assessed in pediatric age group. MATERIALS AND METHODS: This prospective study was conducted at the Pediatric Endocrinology and Adolescent Department between January 2017 and March 2019. Metabolic syndrome and polycystic ovary syndrome diagnosed patients with insulin resistance and/or impaired glucose tolerance, patients with type 2 diabetes mellitus (DM) treated with metformin were enrolled in study. Blood vitamin B12, MMA, homocysteine, holo-TC-II levels and hemogram values were evaluated. RESULTS: Twenty-four patients were enrolled in study. Among these, 15 (62.5%) were female. The mean age of patients was 13.7±2.3 (10-19) years. Sixteen patients were diagnosed with metabolic syndrome and 8 patients were type 2 DM. At 6-month follow-up of all patients, there was no statistically significant difference in terms of vitamin B12, homocysteine, MMA and holo-TC-II levels. A 0.6% decline in vitamin B12 levels were revealed. At 12-month follow-up of 11 patients (45.8%) (6 Type 2 DM, 5 metabolic syndrome), no statistically significant difference was determined in vitamin B12, homocysteine, MMA and holo-TC-II levels. There were 6% decline in vitamin B12 levels and 10.9% increase in homocysteine levels, 5.4% decrease was detected in holo-TC-II level. CONCLUSION: Although no significant changes in the serum vitamin B12, homocysteine, MMA or holo-TC-II levels with metformin therapy were detected, long-term prospective studies with high-dose metformin treatment in pediatric population are needed to confirm our results.
Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Metformina , Deficiência de Vitamina B 12 , Adolescente , Criança , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Homocisteína , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/tratamento farmacológico , Metformina/efeitos adversos , Ácido Metilmalônico , Estudos Prospectivos , Transcobalaminas , Vitamina B 12 , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológicoRESUMO
The pathophysiology of congenital defects of glycosylation (CDG) is complex and the diagnosis has been a challenge because of the overlapping clinical signs and symptoms as well as a large number of disorders. Isoelectric focusing of transferrin has been used as a screening method but has limitations. Individual enzyme or molecular genetic tests have been difficult to perform. In this study, we aimed to describe CDG patients who were referred to from different departments either without a preliminary diagnosis or suspected to have a genetic disorder other than CDG. The patients were diagnosed mainly with a 450 gene next-generation DNA sequencing panel for inborn errors of metabolism, which also included 25 genes for CDG. A total of 862 patients were investigated with the panel, whereby homozygous (10) or compound heterozygous (4) mutations were found in a total of 14 (1.6%) patients. A total of 13 different mutations were discovered, 10 of them being novel. Interestingly, none of the patients was suspected to have a CDG before referral. This report expands the clinical/laboratory findings in patients with CDG and stresses on the fact that CDG should be in the differential list for pediatric patients presented with nonspecific dysmorphic features and neurological delays/regression. Also, next-generation DNA sequencing with panel approach was noticed to have a significant diagnostic potential in patients presented with nonspecific neurologic and dysmorphic findings.
Assuntos
Anormalidades Múltiplas/diagnóstico , Defeitos Congênitos da Glicosilação/diagnóstico , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Doenças do Sistema Nervoso/diagnóstico , Anormalidades Múltiplas/genética , Criança , Pré-Escolar , Defeitos Congênitos da Glicosilação/complicações , Defeitos Congênitos da Glicosilação/genética , Feminino , Glicosilação , Humanos , Lactente , Masculino , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/genéticaRESUMO
INTRODUCTION: Hypophosphatasia (HPP) is caused by mutations in the ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (ALP). Clinical manifestations range from extreme life-threatening lethal forms to no signs or symptoms at all. MATERIALS AND METHODS: Consecutive 30,000 outpatients and inpatients with ALP data were screened retrospectively, out of which 1000 patients were found to have low levels of ALP more than once. Then, patients were evaluated for the symptoms and signs of HPP with further biochemical and genetic analyses. RESULTS: Thirty-seven patients who had severe musculoskeletal pain, recurrent fractures, and tooth anomalies were then screened with substrate and DNA sequencing analyses for HPP. It was determined that eight patients had variants in the ALPL gene. A total of eight different ALPL variants were identified in eight patients. The variants, namely c.244G > C (p.Gly82Arg), c.1444C > T (p.His482Tyr), c.1487A > G (p.Asn493Ser), and c.675_676insCA (p.Met226GlnfsTer52), had not been previously reported. DISCUSSION: Considering the wide spectrum of clinical signs and symptoms, HPP should be among the differential lists of bone, muscle, and tooth abnormalities at any age.
Assuntos
Hipofosfatasia/diagnóstico , Médicos , Adulto , Fosfatase Alcalina/genética , Criança , Pré-Escolar , Feminino , Humanos , Hipofosfatasia/diagnóstico por imagem , Hipofosfatasia/enzimologia , Hipofosfatasia/genética , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estudos RetrospectivosRESUMO
INTRODUCTION: Glycogen storage disease Type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme, encoded by the AGL gene. Two clinical types of the disease are most prevalent: GSD IIIa involves the liver and muscle, whereas IIIb affects only the liver. The classical dietetic management of GSD IIIa involves prevention of fasting, frequent feeds with high complex carbohydrates in small children, and a low-carb-high-protein diet in older children and adults. Recently, diets containing high amount of fat, including ketogenic and modified Atkins diet (MAD), have been suggested to have favorable outcome in GSD IIIa. METHODS: Six patients, aged 3-31 years, with GSD IIIa received MAD for a duration of 3-7 months. Serum glucose, transaminases, creatine kinase (CK) levels, capillary ketone levels, and cardiac parameters were followed-up. RESULTS: In all patients, transaminase levels dropped in response to MAD. Decrease in CK levels were detected in 5 out of 6 patients. Hypoglycemia was evident in 2 patients but was resolved by adding uncooked cornstarch to diet. CONCLUSION: Our study demonstrates that GSD IIIa may benefit from MAD both clinically and biochemically.
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Dieta Rica em Proteínas e Pobre em Carboidratos/métodos , Doença de Depósito de Glicogênio Tipo III/dietoterapia , Adolescente , Adulto , Glicemia/análise , Criança , Pré-Escolar , Feminino , Doença de Depósito de Glicogênio Tipo III/sangue , Humanos , Masculino , Transaminases/sangue , Resultado do Tratamento , Adulto JovemRESUMO
Background/aim: Mucopolysaccharidoses (MPS) are a group of hereditary metabolic diseases. The aim of this study was to share the previously unreported calvarial finding of internal hypertrophy of the occipitomastoid sutures (IHOMS) together with some other well-known cranial MRI findings in this patient series. Materials and methods: A retrospective evaluation was conducted of 80 cranial MRIs of patients who had been diagnosed and followed up with MPS from 2008 to 2019 in our center. Of these patients, 11 had Hurler, 14 had Hunter, 24 had Sanfilippo, 15 had Morquio, 14 had MaroteauxLamy, and 2 had Sly disease. The cranial MRIs were assessed in two main groups as parenchymal intradural cranial MRI findings and extradural calvarial findings. Results: The most common parenchymal intradural cranial MRI findings were white matter signal alterations (n = 51, 63%) and perivascular space enlargements (n = 39, 48%). The most common extradural calvarial findings were J-shaped sella (n = 45, 56%) and tympanic effusion (n = 44, 55%). Although IHOMS was defined in a relatively small number of the patients (n = 12, 15%), the prevalence rate was high in MPS type I (n = 6, 54%). Conclusion: The abnormal cranial MRI findings of the MPS patients, including the newly identified IHOMS, may provide diagnostic clues to differentiate the type of the disease in radiological imaging.
Assuntos
Suturas Cranianas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mucopolissacaridoses/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Suturas Cranianas/patologia , Feminino , Humanos , Hipertrofia , Lactente , Masculino , Mucopolissacaridoses/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located on the left angular region of mandibula. The mass biopsy showed lipid-laden phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells. In NPC, accumulation of cholesterol in tissues could be seen not only in reticuloendothelial and nervous systems, but also in all systems. Our case is important for it being the first case of NPC with submandibular lymphadenopathy characterized with NPC cell infiltration.
Assuntos
Linfonodos/patologia , Doença de Niemann-Pick Tipo C/patologia , Criança , Colesterol , Feminino , Histiócitos/patologia , Humanos , Corpos de Inclusão/patologia , Mandíbula/patologiaRESUMO
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-IdadeRESUMO
Osteopetrosis is a rare genetic condition of reduced osteoclastic bone resorption which causes defective bone remodeling and skeletal sclerosis during growth, having effects on many organs and tissues. Mutation of T-cell immune regulator 1 (TCRG1) gene is the most common genetic defect leading to osteopetrosis, with poor prognosis. The autosomal recessive form presents in the infantile period (also known as malignant infantile osteopetrosis--MIOP), and is characterized by fractures, short stature, hepatosplenomegaly, compressive neuropathies, hypocalcemia and pancytopenia. Being a rare disease with non-specific clinical manifestations, the diagnosis is difficult and usually delayed. Rickets is a characteristic feature of MIOP which results from the defect in osteoclasts to provide a normal Ca/P balance resulting in the poor mineralization of the osteoid. Various treatment options have been suggested for osteopetrosis, but hematopoietic stem cell transplantation still remains the only curative treatment option presently. The authors report the case of a 46-day-old girl with late-onset neonatal hypocalcemia and rickets that was later diagnosed as osteopetrosis. This case report emphasizes that infantile osteopetrosis is an important cause of neonatal hypocalcemia. As irreversible complications develop within the first months of life, immediate diagnosis and early intervention are crucial and may be life-saving.
Assuntos
Hipocalcemia/complicações , Osteopetrose/diagnóstico , Raquitismo/complicações , Conservadores da Densidade Óssea/uso terapêutico , Calcitriol/uso terapêutico , Feminino , Humanos , Lactente , Osteopetrose/complicações , Osteopetrose/tratamento farmacológico , Resultado do TratamentoRESUMO
Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system (https://grenada.lumc.nl/LOVD2/mendelian_genes/variants). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal-recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome.
Assuntos
Morte Súbita/patologia , Febre/genética , Febre/patologia , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/patologia , Mutação , Receptores de Citocinas/genética , Trismo/congênito , Criança , Pré-Escolar , Subunidade alfa do Receptor do Fator Neutrófico Ciliar/genética , Bases de Dados Genéticas , Morte Súbita/epidemiologia , Fácies , Feminino , Febre/epidemiologia , Variação Genética , Deformidades Congênitas da Mão/epidemiologia , Humanos , Hiperidrose , Masculino , Contração Muscular/genética , Reação em Cadeia da Polimerase , Trismo/epidemiologia , Trismo/genética , Trismo/patologiaRESUMO
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by the deficiency of hydrolases involved in the degradative pathway of glycosaminoglycans. In MPS, upper airway obstruction may result from multiple causative factors which may impact severely upon morbidity and mortality. METHODS: We evaluated upper airway obstructive disease and related clinical findings through home sleep study in 19 patients (11 with MPS VI, 4 with MPS I, 4 with MPS II) with MPS followed at Gazi University Pediatric Metabolic Unit. Patients underwent home-based sleep measurements, and sleep respiratory problems were asked in a detailed clinical history. Measurements of apnea, apnea-hypopnea index (AHI), hypopnea index, oxygen desaturation index, and minimal oxygen saturation were obtained through home sleep study. RESULTS: For 19 children, the disorder was normal in 1, mild (AHI=1.5-5/h) in 5, moderate (AHI=5-10/h) in 2, and severe (AHI>10/h) in 11. The prevalence of OSA was 94.7 % (18/19) in patients with MPS. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. Echocardiograms showed evidence of pulmonary hypertension in 13 patients. CONCLUSION: Home sleep study is a quick and accessible screening test to determine the abnormalities of breathing during sleep and enables clinicians to take necessary action for patients with severe manifestations.
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Serviços de Assistência Domiciliar , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/epidemiologia , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose I/epidemiologia , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/epidemiologia , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Adolescente , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Programas de Rastreamento , Polissonografia/instrumentação , TurquiaRESUMO
Early diagnosis for metabolic encephalopathy caused by inborn errors of metabolism is very important for the initiation of early treatment and also for prevention of sequela. Metabolic encephalopathy in the form of seizures can result from many inborn errors of metabolism and considering the large number of disorders causing metabolic encephalopathy, enzyme assays or conventional molecular tests are expensive and take considerably long period of time which results in delayed treatment. In our center we have used next generation DNA sequencing technology as an initial diagnostic test to look for about 700 disorders at the same time for the etiologic diagnosis of a 4-month-old female infant suffering from intractable seizures. The patient was found to have glycine encephalopathy resulting from a previously defined mutation in the GLDC gene. The diagnostic result was obtained much sooner than other conventional investigations. Up to our knowledge, this would be the first case with glycine encephalopathy in the literature who was approached by this novel panel method initially. Although currently, classical evaluation methods such as physical examination, biochemical and conventional molecular investigations are still accepted as the gold standards to clarify the etiology of the metabolic encephalopathy it is obvious that next generation sequence analysis will play a very significant role in the future.
Assuntos
Glicina Desidrogenase (Descarboxilante)/genética , Hiperglicinemia não Cetótica/diagnóstico , Mutação de Sentido Incorreto , Mutação Puntual , Análise de Sequência de DNA/métodos , Sequência de Bases , Análise Mutacional de DNA/métodos , Feminino , Genes Recessivos , Glicina/sangue , Glicina/líquido cefalorraquidiano , Glicina Desidrogenase (Descarboxilante)/deficiência , Homozigoto , Humanos , Hiperglicinemia não Cetótica/enzimologia , Hiperglicinemia não Cetótica/genética , Hiperglicinemia não Cetótica/metabolismo , Lactente , Dados de Sequência Molecular , Convulsões/etiologia , Alinhamento de Sequência , Homologia de Sequência do Ácido NucleicoRESUMO
GRACILE syndrome is a rare autosomal recessive disease characterized by fetal growth retardation, Fanconi type aminoaciduria, cholestasis, iron overload, profound lactic acidosis, and early death. It is caused by homozygosity for a missense mutation in the BCS1L gene. The BCS1L gene encodes a chaperone responsible for assembly of respiratory chain complex III. Here we report that a homozygous mutation c.296C > T (p.P99L), in the first exon of BCS1L gene found in an affected 2-month-old boy of asymptomatic consanguineous parents results in GRACILE syndrome. This genotype is associated with a severe clinical presentation. So far no available treatments have changed the fatal course of the disease, and the metabolic disturbance responsible is still not clearly identified. Therefore, providing prenatal diagnosis in families with previous affected infants is of major importance. Mitochondrial disorders are an extremely heterogeneous group of diseases sharing, in common, the fact that they all ultimately impair the function of the mitochondrial respiratory chain. A clinical picture with fetal growth restriction, postnatal lactacidosis, aminoaciduria, hypoglycemia, coagulopathy, elevated liver enzymes, and cholestasis should direct investigations on mitochondrial disorder.
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Acidose Láctica/genética , Colestase/genética , Complexo III da Cadeia de Transporte de Elétrons/genética , Retardo do Crescimento Fetal/genética , Hemossiderose/genética , Erros Inatos do Metabolismo/genética , Doenças Mitocondriais/congênito , Aminoacidúrias Renais/genética , ATPases Associadas a Diversas Atividades Celulares , Humanos , Lactente , Masculino , Doenças Mitocondriais/genética , Mutação de Sentido IncorretoRESUMO
Inborn errors of metabolism (IEMs) are a group of genetic diseases that occur due to the either deficiency of an enzyme involved in a metabolic/biochemical pathway or other disturbances in the metabolic pathway including transport protein or activator protein deficiencies, cofactor deficiencies, organelle biogenesis, maturation or trafficking problems. These disorders are collectively significant due to their substantial impact on both the well-being and survival of affected individuals. In the quest for effective treatments, enzyme replacement therapy (ERT) has emerged as a viable strategy for patients with many of the lysosomal storage disorders (LSD) and enzyme substitution therapy in the rare form of the other inborn errors of metabolism including phenylketonuria and hypophosphatasia. However, a major challenge associated with enzyme infusion in patients with these disorders, mainly LSD, is the development of high antibody titres. Strategies focusing on immunomodulation have shown promise in inducing immune tolerance to ERT, leading to improved overall survival rates. The implementation of immunomodulation concurrent with ERT administration has also resulted in a decreased occurrence of IgG antibody development compared with cases treated solely with ERT. By incorporating the knowledge gained from current approaches and analysing the outcomes of immune tolerance induction (ITI) modalities from clinical and preclinical trials have demonstrated significant improvement in the efficacy of ERT. In this comprehensive review, the progress in ITI modalities is assessed, drawing insights from both clinical and preclinical trials. The focus is on evaluating the advancements in ITI within the context of IEM, specifically addressing LSDs managed through ERT.
Assuntos
Terapia de Reposição de Enzimas , Tolerância Imunológica , Humanos , Doenças por Armazenamento dos Lisossomos/tratamento farmacológico , Doenças por Armazenamento dos Lisossomos/imunologia , Doenças por Armazenamento dos Lisossomos/terapia , Erros Inatos do Metabolismo/imunologia , Erros Inatos do Metabolismo/tratamento farmacológico , Erros Inatos do Metabolismo/terapia , AnimaisRESUMO
ABBREVIATIONS: ESR: erythrocyte sedimentation rate; Hb: haemoglobin; HSP: Henoch-Schönlein purpura; WCC: white-cell count.
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Doença Celíaca , Escorbuto , Humanos , Masculino , Criança , Escorbuto/diagnóstico , Escorbuto/complicações , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Sedimentação SanguíneaRESUMO
AIM: Dietary therapy of glycogen storage disease I (GSD I) is based on frequent feeding, with a high intake of complex carbohydrates (supplied by uncooked cornstarch), restriction of sugars, and a lower amount of lipids. There is limited information about the dietary regimen in patients with GSD, which might affect the intestinal luminal pH and microbiota composition. The aim of this study to investigate the intestinal microbiota composition in patients with GSD receiving diet treatment. METHOD: Twelve patients who were followed up with GSD I after the diagnosis receiving diet therapy and 11 healthy children have been enrolled. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. RESULTS: A significant difference was found for beta-diversity between the GSD group and controls. A significantly lower abundance of Firmicutes and higher abundance of Actinobacteria was found in GSD group compared to the controls. Akkermansia, Pseudoalteromonas, Uruburella, and Castellaniella were dominant in the GSD patients at the genus level, while Faecalibacterium, Bacterioides, Gemmiger, Parabacteroides in the control group. At species level, Faecalibacterium prausnitzii decreased, and Akkermansia muciniphila were dominant in children with GSD. DISCUSSION: There is a substantial change in the composition of the gut microbiota, reduction of F. prausnitzii and an increase of A. muciniphila in children with GSD receiving consumption of uncooked cornstarch. Alterations of the intestinal microbiota might be related with the disease itself or dietary restrictions in patients with GSD, however, in certain condition, dysbiosis can negatively affect the course and make it difficult to control the disease.
Assuntos
Microbioma Gastrointestinal , Doença de Depósito de Glicogênio Tipo I , Humanos , Masculino , Feminino , Criança , Pré-Escolar , Fezes/microbiologia , RNA Ribossômico 16S , Lactente , Dieta/métodos , Estudos de Casos e Controles , Disbiose/microbiologiaRESUMO
BACKGROUND: Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the MAN2B1 gene. It manifests with clinical features, including intellectual disability, hearing impairment, coarse facial appearance, skeletal anomalies, immunodeficiency, central nervous system involvement, psychiatric comorbidities, corneal opacity, and hepatosplenomegaly. This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics. METHOD: Sixteen patients diagnosed with alpha-mannosidosis who presented to four pediatric metabolic units were included in the study. The patients' medical records were analyzed and data on demographics, clinical presentation and laboratory findings were recorded. RESULTS: Of the 16 patients (6 females, 10 males) with alpha mannosidosis included in the study, the mean age at the time of diagnosis was 79.4 ± 56.1 (16-208) months, and the mean diagnosis delay time was 57.9 ± 51.9 (4-181) months. Hearing loss was the primary manifestation found in seven out of 16 patients (43.8%), followed by speech delay in 37.8%. On clinical follow-up, 87.5% of patients experienced recurrent infections, mainly in the upper respiratory tract, with 12 requiring the use of a hearing aid. Hepatomegaly was found in six out of 13 patients who received abdominal ultrasonography; two out of 12 patients who underwent echocardiography were found to have mitral valve prolapse (16.6%). Upon neurological evaluation, five patients displayed no neurological manifestation. Delayed language development was observed in nine (56.3%) patients, intellectual disability in eight (50%) patients, and hypertonicity was identified in one (6.3%) patient with the severe form of the disease. Homozygous c.2477C>A (p.Ser826Ter) and homozygous c.967G>A (p.Glu323Lys) novel variants were detected in four patients and one patient, respectively. The most common variant observed in the study was c.2477C>A (p.Ser826Ter). CONCLUSION: The present study identified two novel MAN2B1 variants. An evaluation of the long-term outcome of alpha-mannosidosis, in which the early initiation of enzyme replacement therapy (ERT) may lead to a better clinical outcome, can permit a better analysis of the effect of ERT on the natural progression of the disease.