A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum.

Background: Leigh syndrome spectrum (LSS) is a novel nomenclature that encompasses both classical Leigh syndrome and Leigh-like phenotypes. Given the heterogeneity of disease presentation, a new consensus published recently addressed the main issues and proposed general guidelines towards diagnosis. Based on these recommendations, we developed a simple pipeline that can be useful in the diagnosis of LSS.

Phenotyping mitochondrial glutamyl-tRNA synthetase deficiency (EARS2): A case series and systematic literature review.

Mitochondrial glutamyl-aminoacyl tRNA synthetase deficiency, stemming from biallelic mutations in the EARS2 gene, was first described in 2012. With <50 cases reported globally, this condition exhibits a distinct phenotype of neonatal or childhood-onset, often referred to as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). It has also been one of the few reversible mitochondrial disorders described.

Portuguese Neonatal Screening Program: A Cohort Study of 18 Years Using MS/MS.

The Portuguese Neonatal Screening Program (PNSP) conducts nationwide screening for rare diseases, covering nearly 100% of neonates and screening for 28 disorders, including 24 inborn errors of metabolism (IEMs). The study's purpose is to assess the epidemiology of the screened metabolic diseases and to evaluate the impact of second-tier testing (2TT) within the PNSP. From 2004 to 2022, 1,764,830 neonates underwent screening using tandem mass spectrometry (MS/MS) to analyze amino acids and acylcarnitines in dried blood spot samples.

The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study.

Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs.

History of Neonatal Screening of Congenital Hypothyroidism in Portugal.

Congenital hypothyroidism (CH) leads to growth and development delays and is preventable with early treatment. Neonatal screening for CH was initiated in Portugal in 1981. This study examines the history of CH screening in the country.

Iodineminho Study: Iodine Supplementation and Prevalence of Iodine Deficiency In Pregnant Women.

Context: Iodine is necessary for proper brain development. The prevalence of iodine deficiency in Portuguese pregnant women led the health authorities, in 2013, to recommend iodine supplementation for women in preconception, throughout pregnancy, and during lactation.

Objective: This work aimed to assess the effect of iodine supplementation initiated in the preconception or the first trimester of pregnancy on the prevalence of iodine deficiency and maternal thyroid status.

Pharmacogenetic Variants Can Influence Optical Medication Use.

Introduction: Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079).

Neonatal Glycogen Storage Disease Type IA: A Rare Presentation.

Glucose homeostasis is essential for energy production and the central nervous system function, depending on glycogen metabolism. Glycogen storage diseases (GSD) are caused by enzymatic defects of the glycogen degradation and mainly involve the liver since the inhibition of hepatic glycogen breakdown results in its excessive storage and hepatomegaly. Other findings are hypoglycemia and hyperlactatemia and consequent neurological symptoms.

Pilot Study on Newborn Screening for Spinal Muscular Atrophy.

Introduction: Newborn screening (NBS) in Portugal is a significant public health measure to provide early detection for specific disorders so that early treatment is possible. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. Its incidence is estimated in 1.

Glutaric Acidemia Type 1: Diagnosis, Clinical features, and Outcome in a Portuguese Cohort.

Introduction: Glutaric acidemia type 1 (GA1) is a rare autosomal recessive disorder characterized by a deficiency of glutaryl-CoA dehydrogenase, resulting in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid, and glutarylcarnitine, especially in the brain. GA1-affected children are clinically characterized by macrocephaly. Neurological abnormalities usually appear between 6 and 18 months of age, often triggered by a catabolic event.

Portuguese Neonatal Screening Programme: A Retrospective Cohort Study of 18 Years of MS/MS.

Introduction: The Portuguese Neonatal Screening Programme (PNSP) identifies patients with rare diseases through nationwide screening. Currently, 27 diseases are diagnosed, amongst which are 24 Inborn Errors of Metabolism (IEM), covering approximately 100% of neonates (1). In 2004, the national laboratory implemented a new screening method, tandem mass spectrometry (MS/MS) to test for amino acids and acylcarnitines.

SERAC1 Deficiency- A New Phenotype.

Introduction - SERAC1 deficiency phenotype range from MEGD(H)EL syndrome, the most severe, to juvenile complicated spastic paraplegia, to adult-onset dystonic features (in only one patient). The MEGD(H)EL syndrome is characterized by (3-methylglutaconic aciduria with deafness-dystonia, [hepatopathy], encephalopathy, and Leigh-like syndrome). Biochemical abnormalities: elevated urinary 3 - metilglutaconic and 3-metilglutaric acids, high lactate and alanine in serum.

Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era.

Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life.

Role of gluteus maximus and medius activation in the lower limb biomechanical control during functional single-leg Tasks: A systematic review.

Objectives: Single-leg (SL) tasks are included as assessment and intervention strategies in several dysfunctions due to the inherent motor control requirement. The recruitment of gluteus maximus (GMAX) and medius (GMED) muscles is essential for proper biomechanical control of the knee and hip joints. The study aims to identify the role of gluteal activation in the biomechanical control of the lower limb during SL tasks.

Diagnosis across a cohort of "atypical" atypical and complex parkinsonism.

Introduction: The diagnostic approach for adulthood parkinsonism can be challenging when atypical features hamper its classification in one of the two main parkinsonian groups: Parkinson's disease or atypical parkinsonian syndromes (APS). Atypical features are usually associated with non-sporadic neurodegenerative causes.

Methods: Retrospective analysis of patients with a working clinical diagnosis of "atypical" APS and complex parkinsonism.

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.

Exercise training counteracts the cardiac metabolic remodelling induced by experimental pulmonary arterial hypertension.

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment.

Iodine supplementation: compliance and association with adverse obstetric and neonatal outcomes.

Objectives: Over 1.9 billion people worldwide are living in areas estimated to be iodine insufficient. Strategies for iodine supplementation include campaigns targeting vulnerable groups, such as women in pre-conception, pregnancy and lactation.

The c.1901C>T Variant: A Founder Variant in the Portuguese Population with Severe Impact in mRNA Splicing.

Hereditary diffuse gastric cancer (HDGC) caused by variants predisposes to early-onset diffuse gastric (DGC) and lobular breast cancer (LBC). In Northern Portugal, the unusually high number of HDGC cases in unrelated families carrying the c.1901C>T variant (formerly known as p.

Role of RNA in Molecular Diagnosis of MADD Patients.

The electron-transfer flavoprotein dehydrogenase gene () encodes the ETF-ubiquinone oxidoreductase (ETF-QO) and has been reported to be the major cause of multiple acyl-CoA dehydrogenase deficiency (MADD). In this study, we present the clinical and molecular diagnostic challenges, at the DNA and RNA levels, involved in establishing the genotype of four MADD patients with novel variants: a missense variant, two deep intronic variants and a gross deletion. RNA sequencing allowed the identification of the second causative allele in all studied patients.

Parkinsonism and iron deposition in two adult patients with L-2-hydroxiglutaric aciduria.

L-2-hydroxiglutaric aciduria (L2HGA) is a rare, childhood-onset, organic aciduria, with characteristic clinical (cerebellar ataxia) and neuroimaging (subcortical leukodystrophy) features. Movement disorders in this condition are usually of hyperkinetic type. Herein is reported the case of two adult siblings with recent L2HGA diagnosis, presenting with dopa-responsive parkinsonism and MRI iron deposition.

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010.

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies.