Acquired Vitamin B12 Deficiency in Newborns: Positive Impact on Newborn Health through Early Detection

The early diagnosis of and intervention in vitamin B12 deficiency in exclusively breastfed infants by mothers with low vitamin B12 is crucial in preventing possible irreversible neurologic damage, megaloblastic anemia, and failure to thrive. We assess the usefulness of the early detection of asymptomatic B12 deficiency related to acquired conditions and highlight the importance of monitoring serum vitamin B12 levels during pregnancy. We describe demographic, clinical, dietary, and biochemical data, including the evolution of a vitamin B12 deficiency's functional biomarkers. We enrolled 12 newborns (5 males) with an age range of 1-2 months old that were exclusively breastfed and asymptomatic. These cases were referred to our metabolic unit due to alterations in expanded newborn screening: high levels of methylmalonic acid and/or total homocysteine (tHcy). All mothers were under a vegetarian diet except three who had abnormal B12 absorption, and all presented low or borderline serum B12 level and high plasma levels of tHcy. Supplementation with oral vitB12 re-established the metabolic homeostasis of the mothers. In infants, therapy with an intramuscular injection of 1.0 mg hydroxocobalamin led to the rapid normalization of the metabolic pattern, and a healthy outcome was observed. Acquired B12 deficiency should be ruled out before proceeding in a differential diagnosis of cobalamin metabolism deficits, methylmalonic acidemia, and homocystinuria.info:eu-repo/semantics/publishedVersio

Défice do transportador de creatina : até onde investigar a causa de um atraso do desenvolvimento?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014Creatine Deficiency Syndromes are a group of genetic diseases X-linked or autosomal recessive disorders, with a prevalence between 0.3 and 3.5% in males. Several cases of Creatine Transporter Deficiency caused by SLC6A8 gene mutation have been already reported. Recent studies have established an association between low levels of creatine in the brain and severe neurological dysfunctions such as encephalomyopathies or mitochondrial myopathies. Creatine deplection has a high impact in brain function leading to mental retardation, compromises language development and causes extrapyramidal symptoms. Additional features can include short stature, hyperactive, autistic behaviour and phenotypic characteristics, such as microcephaly, muscular hypotonia and hypotrophy. The diagnosis of this disease is challenging because of its nonspecific manifestations combining early developmental delay with autism behaviour leading to a broad number of different pathologies to be considered for diagnosis.The effects of arginine and glycine supplementation and high doses of creatine monohydrate on improving intellectual and behavioral disorders are still being investigated. The prognosis is reserved. Author report a clinical case of Creatine Transporter Deficiency with a short review of the literature.Doenças do metabolismo da creatina são um grupo de doenças genéticas que se transmitem de modo hereditário ligado ao cromossoma X ou autossómico recessivo, cuja prevalência está compreendida entre 0,3 e 3,5% no sexo masculino, existindo já vários casos reportados de Deficiência do Transportador da Creatina ligada ao gene SLC6A8. Estudos recentes estabelecem uma associação entre níveis baixos de creatina a nível cerebral e a presença de severas disfunções neuronais como encefalomiopatias ou miopatias mitocondriais. A diminuição dos níveis de creatina afeta o cérebro em grande escala traduzindo-se em atraso do desenvolvimento psicomotor com dissociação negativa na área da linguagem e manifestações extra-piramidais. Adicionalmente pode manifestar-se por alterações no crescimento e psico-comportamentais e alterações fenotípicas como a microcefalia, hipotonia e hipotrofia muscular. O diagnóstico da Deficiência do Transportador da Creatina é desafiante pois manifesta-se de modo inespecífico por atraso do desenvolvimento psicomotor (ADPM) e simultaneamente por perturbações do espetro do autismo, sendo por isso necessário fazer um diagnóstico diferencial com diferentes patologias associadas a atrasos cognitivos que se desenvolvem precocemente. O tratamento combinado com suplementos de arginina e glicina e doses elevadas de creatina monohidratada, está atualmente em investigação, como tal o prognóstico é reservado. Este artigo procura expor e relatar um caso clínico de Défice de Transportador de Creatina acompanhado de uma pequena revisão teórica e descrição da investigação laboratorial e diagnósticos diferenciais a ponderar

Pharmacological Prescription Dilemmas in Obese Children and Adolescents: Date of submission: 23-09-2017 | Date of acceptance: 24-04-2018 | Published: 06-11-2018

Paediatric obesity is a serious public health concern. We daily face the need to medicate obese children, whether in the context of acute or chronic diseases. Prescribing in these patients becomes a real challenge as there are scarce specific recommendations available to optimise drug dosing. The main pharmacokinetic parameter which is altered in obesity is the volume of distribution, determined by the physiochemical properties of the drug, such as lipophilicity and protein binding. There is no single size descriptor that is undeniably better for dosing drugs in obese patients. We searched for the terms children, pharmacokinetic, obesity, overweight, body mass index, lean body weight, ideal body weight and specific drugs in the PubMed, Medline and Cochrane databases between 2006 and 2016. A chart to identify the most adequate body size descriptor for different types of drugs is proposed, providing foundations for safer drug dose calculation. There is an urgent need to raise awareness for prescription rationality and harmonising the current existing guidelines.Paediatric obesity is a serious public health concern. We daily face the need to medicate obese children, whether in the context of acute or chronic diseases. Prescribing in these patients becomes a real challenge as there are scarce specific recommendations available to optimise drug dosing. The main pharmacokinetic parameter which is altered in obesity is the volume of distribution, determined by the physiochemical properties of the drug, such as lipophilicity and protein binding. There is no single size descriptor that is undeniably better for dosing drugs in obese patients. We searched for the terms children, pharmacokinetic, obesity, overweight, body mass index, lean body weight, ideal body weight and specific drugs in the PubMed, Medline and Cochrane databases between 2006 and 2016. A chart to identify the most adequate body size descriptor for different types of drugs is proposed, providing foundations for safer drug dose calculation. There is an urgent need to raise awareness for prescription rationality and harmonising the current existing guidelines

Inborn errors of metabolism in a tertiary pediatric intensive care unit

© 2020. Thieme. All rights reserved. Georg Thieme Verlag KG,Few studies exist describing resources and care of pediatric patients with inborn errors of metabolism (IEM) admitted to pediatric intensive care unit (PICU). This study aims to characterize the PICU admissions of these patients to provide better diagnostic and therapeutic care in the future. Retrospective analysis of pediatric patients with IEM admitted to the PICU of a tertiary care center at a metabolic referral university hospital from 2009 to 2019 was included. Clinical information and demographic data were collected from PICU clinical records. During this period, 2% ( n = 88 admissions, from 65 children) out of 4,459 PICU admissions had clinical features of IEM. The median age was 3 years (range: 3 days-21 years) and 33 were male. Median age at diagnosis was 3 months; 23/65 patients with intoxication disorders, 21/65 with disorders of energy metabolism, 17/65 with disorders of complex molecules, and 4/65 with other metabolic diseases (congenital lipodystrophy, Menkes' disease, hyperammonemia without a diagnosis). From a total of 88 admissions, 62 were due to metabolic decompensation (infection-38, neonatal period decompensation-14, external accident-5, prolonged fasting-2, and therapeutic noncompliance-3) and 26 elective admissions after a scheduled surgery/elective procedure. The most frequent clinical presentations were respiratory failure (30/88) and neurological deterioration (26/88). Mechanical ventilation was required in 30 patients and parenteral nutrition in 6 patients. Extracorporeal removal therapy was required in 16 pediatric patients (12 with maple syrup urine disease and 4 with hyperammonemia) with a median duration of 19 hours. The median length of PICU stay was 3.6 days (3 hours-35 days). Eight patients died during the studied period (cerebral edema-2, massive hemorrhage-5, and malignant arrhythmia-1). Acute decompensation was the main cause of admission in PICU in these patients. The complexity of these diseases requires specialized human and technical resources, with an important impact on the recovery and survival of these patients.info:eu-repo/semantics/publishedVersio

Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway