What will it take? Perspectives from five low- and middle-income countries on opportunities and challenges of introducing new maternal vaccines.

Background: New vaccines for pregnant women have recently been introduced in some high-income countries to protect infants in early life. Implementing maternal immunisation (MI) successfully in low- and middle-income countries will require planning and adaptations to immunisation and maternal health programs. To inform cost of MI delivery studies, we gathered perspectives from key stakeholders in five countries (Bangladesh, Ghana, Kenya, Mozambique, and Nepal) regarding health system requirements, opportunities, and challenges to introducing new maternal vaccines into routine health programs.

Gathering information on maternal immunization readiness in Bangladesh, Ghana, Kenya, Mozambique, and Nepal: Applying a WHO checklist.

New respiratory syncytial virus (RSV) maternal vaccines have begun roll out in some countries, with efforts in progress to broaden access worldwide and shorten the timeline to access for low- and middle-income countries (LMICs). Prior to new maternal immunization (MI) introductions, countries will need to evaluate their capacity and readiness for successful introduction. The World Health Organization's Maternal Immunization and Antenatal Care Situation Analysis (MIACSA) project (2016-2019) developed a checklist for countries to self-evaluate their capacity to introduce new maternal vaccines.

Treatment of congenital disorders of glycosylation: An overview.

While the identification and diagnosis of congenital disorders of glycosylation (CDG) have rapidly progressed, the available treatment options are still quite limited. Mostly, we are only able to manage the disease symptoms rather than to address the underlying cause. However, recent years have brought about remarkable advances in treatment approaches for some CDG.

Natural history of three late-diagnosed classic Galactosemia patients.

The authors report the natural history of three patients with late-diagnosed Classic Galactosemia (CG) (at 16, 19 and 28 years). This was due to a combination of factors: absence of neonatal screening, absence of some typical acute neonatal symptoms, and negative galactosemia screening. This report underlines the value of neonatal screening and the importance of further diagnostic testing in case of late-onset manifestations.

Diagnostic accuracy and the first genotype-phenotype correlation in glycogen storage disease type V.

Background: Glycogen storage disease type V (GSDV) is an autosomal recessive metabolic condition caused by pathogenic PYGM variants. This is an underdiagnosed condition as it presents with exercise intolerance in children. We reviewed the GSDV cases of a tertiary hospital center to assess diagnostic timing/accuracy, as well as potential clinical/analytical predictors of such factors.

Challenges in the Definitive Diagnosis of Niemann-Pick Type C-Leaky Variants and Alternative Transcripts.

Niemann-Pick type C (NPC, ORPHA: 646) is a neuro-visceral, psychiatric disease caused predominantly by pathogenic variants in the gene or seldom in . The rarity of the disease, and its wide range of clinical phenotypes and ages of onset, turn the diagnosis into a significant challenge. Other than the detailed clinical history, the typical diagnostic work-up for NPC includes the quantification of pathognomonic metabolites.

Impact of Structural GLA Protein Changes on Peripheral GLA Activity and Substrate Accumulation in Fabry Disease Patients.

Introduction: Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, leading to decreased/absent α-galactosidase activity. In clinical practice, enzyme activity and substrate/byproduct accumulation play a role in diagnosis and disease-monitoring biomarkers. However, interpreting biomarker levels is not straightforward and can change according to the underlying GLA protein abnormality.

Clinical and Laboratory Findings on Glycogen Storage Disease Type V: Results from a Retrospective Observational Study in a Tertiary Hospital.

Introduction - Glycogen storage disease type V (GSDV, MIM #232600) is an autosomal recessive metabolic myopathy caused by pathogenic variants in the PYGM gene. The characteristic symptoms of exercise intolerance, myalgia, and cramps, which improve after a few minutes of rest, are frequently unrecognized in affected children. When there is clinical suspicion, the initial approach with a forearm exercise test has diagnostic value by detecting low post-exercise plasma lactate-to-ammonia ratio values.

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.

Assessing the effects of PMM2 variants on protein stability.

Phosphomannomutase 2 deficiency, PMM2-CDG, is the most frequent disorder of protein N-glycosylation. It is an autosomal recessive disease with a broad clinical and biochemical phenotype. Trying to predict the impact of novel variants is often a challenge due to the high number of variants and the difficulty to establish solid genotype-phenotype correlations.

Genotype-Phenotype Correlations in PMM2-CDG.

PMM2-CDG is a rare disease, causing hypoglycosylation of multiple proteins, hence preventing full functionality. So far, no direct genotype-phenotype correlations have been identified. We carried out a retrospective cohort study on 26 PMM2-CDG patients.

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?

PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production.

Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.

Purpose: Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature.

SLC37A4-CDG: Second patient.

Recently, a disorder caused by the heterozygous de novo c.1267C>T (p.R423*) substitution in has been described.

SLC35A2-CDG: Novel variant and review.

encodes the X-linked transporter that carries uridine diphosphate (UDP)-galactose from the cytosol to the lumen of the Golgi apparatus and the endoplasmic reticulum. Pathogenic variants have been associated to a congenital disorder of glycosylation (CDG) with epileptic encephalopathy as a predominant feature. Among the sixty five patients described so far, a strong gender bias is observed as only seven patients are males.

Congenital Disorders of Glycosylation in Portugal-Two Decades of Experience.

Objective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years.

Study Design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed.

NPC1 silent variant induces skipping of exon 11 (p.V562V) and unfolded protein response was found in a specific Niemann-Pick type C patient.

Background: Niemann-Pick type C (NPC, MIM #257220) is a neuro-visceral disease, caused predominantly by pathogenic variants in the NPC1 gene. Here we studied patients with clinical diagnosis of NPC but inconclusive results regarding the molecular analysis.

Methods: We used a Next-Generation Sequencing (NGS)-panel followed by cDNA analysis.

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1-CDG. PGM1-CDG usually manifests as a multisystem disease.

Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease - A Rare Case Concerning Gene Pleiotropy.

Co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD) has been recently described. It is caused by a non-coding variant in the promoter region for phosphomannomutase 2 (), c.-167G>T, both in homozygous or compound heterozygous variants with deleterious coding.

Consensus guideline for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation.

Mannose phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) deficiency is a rare subtype of congenital disorders of protein N-glycosylation. It is characterised by deficiency of MPI caused by pathogenic variants in MPI gene. The manifestation of MPI-CDG is different from other CDGs as the patients suffer dominantly from gastrointestinal and hepatic involvement whereas they usually do not present intellectual disability or neurological impairment.

A Systematic Review Investigating the Relation Between Animal-Source Food Consumption and Stunting in Children Aged 6-60 Months in Low and Middle-Income Countries.

Animal-source foods (ASFs) are a food group of interest for interventions aimed at reducing stunting and other inadequate growth measures in early childhood. The aim of this systematic review was to examine the relation between ASF consumption and stunting in children aged 6-60 mo in low- and middle-income countries (LMICs). The secondary aim was to examine the relation between ASF consumption and other indicators of growth and development (length/height, weight, head circumference, and anemia).

Genotype-phenotype correlations and BH estimated responsiveness in patients with phenylketonuria from Rio de Janeiro, Southeast Brazil.

Background: Genetic heterogeneity and compound heterozygosis give rise to a continuous spectrum of phenylalanine hydroxylase deficiency and metabolic phenotypes in phenylketonuria (PKU). The most used parameters for evaluating phenotype in PKU are pretreatment phenylalanine (Phe) levels, tolerance for dietary Phe, and Phe overloading test. Phenotype can vary from a "classic" (severe) form to mild hyperphenylalaninemia, which does not require dietary treatment.