Resumo em Inglês:

Abstract A descriptive, retrospective, cross-sectional study was conducted, evaluating data from newborn (NB) samples sent to the PNDN between January 2018 and December 2023. Samples taken by heel prick on Whatman 903 filter paper and analyzed by fluorometric immunoassay for the quantification of immunoreactive trypsin (IRT) were included. An IRT(+)/IRT(+) strategy was adopted, with diagnostic confirmation by sweat test. Descriptive statistics were used to analyze the incidence of CF. Variability in the incidence of CF was observed between 2018 and 2023, with a peak in 2020 (1/4,431) followed by a decrease in subsequent years. In the temporal trend analysis, it was observed that the incidence of CF does not follow a simple linear trend, indicating more complex fluctuations over time, but with an increase in the average incidence being statistically significant (p=0.0385). Management indicators showed improvements in sample processing and analysis times over the years. The distribution of confirmed CF cases by health region did not reflect statistically significant differences, with a higher concentration in the Central Department (26%). The incidence of CF in Paraguay shows a stable trend in recent years. Improvements in management indicators and regional disparities in disease incidence highlight the need for differentiated approaches to CF detection.

Resumo em Inglês:

Abstract Introduction: Creatinine (Cr) is a chemical waste breakdown product of creatine and Cr levels can assist in diagnosing the functioning of the kidneys and it can be measured as part of basic- or comprehensive metabolic panel tests. Urinary creatinine (UCr) is often used to calculate urine analyte concentrations of metabolic panel tests, which emphasizes the need for infallibly accurate UCr results. Methods: Cr analysis was performed using an enzymatic Cr analysis kit. A total of four ERNDIM EQA urine samples with known Cr values and four samples with unknown Cr values were used in this study. Results: For the known Cr value samples, a percentage difference from the known value was calculated for each comparison. The rotated and centrifuged result comparison showed the lowest % difference from the known UCr value for known samples 1 and 4: 0.31% and 0.34% respectively. The centrifuged comparison showed lower % differences compared to those of the initial and repeat results. For the unknown UCr value samples results, standard deviations, averages and %CV (coefficient of variance) were calculated. Conclusion: This feasibility study, however small, is suggestive proof that there is indeed necessity and room for optimization when it comes to standardisation of pre-treatment procedures prior to UCr analysis.

Resumo em Inglês:

Abstract Hepatic glycogen storage diseases (GSD) are a group of rare hereditary metabolic diseases characterized by abnormalities in enzymes that regulate glycogen synthesis or degradation. Treatment is essentially dietary, with frequent administration of raw uncooked cornstarch (UCCS) to avoid hypoglycemia, in addition to the restriction of sucrose, fructose, and lactose. Nutritional deficiencies in these patients are believed to result from dietary restrictions that exclude key sources of essential vitamins. This study aimed to investigate serum levels and adequacy of dietary intake of B vitamins in patients with GSD. This is a cross-sectional study, with patients over 5 years old, diagnosed with GSD and undergoing treatment with UCCS. Clinical data were collected, in addition to the dosage of B vitamins and a 3-day food record. Fifteen patients were included, six of them reported daily use of multivitamins. Serum dosage showed that all B complex vitamins, except for vitamin B2, were within reference values. The adequacy of dietary intake of vitamins was at least 78%, except for vitamin B9. There was no correlation between dosage and vitamin intake.

Resumo em Inglês:

Abstract Niemann-Pick type C disease (NPC) is a rare autosomal recessive lysosomal storage disorder, most often caused by biallelic pathogenic variants in the NPC1 gene (~95 %). While the central nervous system is typically involved, the role of the peripheral nervous system in NPC remains underexplored. We describe a case series of nine individuals with genetically confirmed NPC1 mutations, followed at a reference center for inborn errors of metabolism in Bahia, Brazil. Clinical signs of peripheral neuropathy were observed in all patients; seven underwent electromyography and nerve conduction studies, with abnormalities detected in six. Predominantly, axonal sensorimotor polyneuropathy was found, with demyelinating features in two early infantile cases. All NPC phenotypic subtypes exhibited signs of peripheral involvement, including altered reflexes, distal muscle weaknessand atrophy. These findings suggest that peripheral neuropathy may be a more common and underrecognized feature of NPC1-related disease. Further studies, including nerve biopsies and longitudinal assessments, are needed to better understand the PNS’s contribution to disease progression.

Resumo em Inglês:

Abstract Gaucher disease type 1 (GD1) is the most common lysosomal storage disorder, characterized by hepatomegaly, splenomegaly, anemia, thrombocytopenia, and skeletal manifestations, which significantly affect quality of life. This systematic review aimed to assess the current state of the disease, focusing on skeletal manifestations. A systematic search was conducted between 2000 and February 2024 in multiple languages using PRISMA-ScR and JBI methods. A total of 96 studies were identified: 23 systematic reviews, 23 descriptive studies, 17 case reports, 13 experimental studies, 10 retrospective studies, 4 observational studies, 4 prospective studies, and 2 cross-sectional studies. The highest number of articles on the topic was published in 2015, and the countries with the most publications were the USA, Italy, Brazil, and Argentina over the 23 years covered in the search. These studies cover various aspects of GD1, including skeletal features, patient phenotypes, clinical annotations, diagnostics, therapies, and patient perspectives. Despite advances, challenges such as disease heterogeneity and inconsistent results persist. This review underscores the importance of further research to improve understanding and management of GD1, with an emphasis on skeletal manifestations.

Resumo em Inglês:

Abstract Fabry disease is an X-linked genetic disorder caused by GLA gene variants, resulting in a lysosomal enzyme deficiency of the acid hydrolase α-galactosidase A, with a progressive accumulation of globotriaosylceramide that mainly affects the cardiovascular, renal, and nervous systems. In September 2023, a local group of physicians, experts in Fabry disease patient management, convened in a face-to-face meeting to discuss and review some controversial aspects, based on their experience and the updated literature. This study aims to report the results of the review. A non-exhaustive literature search was conducted using the Embase and PubMed databases. The review highlighted that early initiation of treatment in children with “classic” forms has been associated with better outcomes, based on the reduction in biomarkers, improvement in symptoms, and stabilization of renal and cardiovascular function. Although the dose of enzyme replacement therapy has been a controversial issue, the personal experience of the authors, long-term data, and new therapeutic guidelines suggest that a dose of 1 mg/kg every other week should be considered the first-line treatment for males with the “classic” phenotype.

Resumo em Inglês:

Abstract 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD) is a rare metabolic disease. Early symptoms include poor feeding, seizures, hypotonia and impaired psychomotor development. Acute metabolic crisis can cause encephalopathy with high risk of neurological sequelae or death. Casuistic, we here report a nine-year old Danish girl with HIBCHD treated with intravenous high-dose methylprednisolone when presenting with encephalopathy during acute metabolic crisis. Presentation of acute encephalopathy with basal ganglia changes seen on MRI was regarded as acute disseminated encephalomyelitis (ADEM) leading to intravenous high-dose methylprednisolone treatment. The effect of methylprednisolone was profound, not only on the acute neurological symptoms, but also accelerated the development of the child. After re-evaluation of MR images, Whole Genome Sequencing (WGS) confirmed the diagnosis HIBCHD. The high-dose methylprednisolone treatment regime was repeated in a following severe metabolic crisis presenting with acute encephalopathy, dystonia and spasticity. The child survived and after rehabilitation neurological sequelae are present but considerably reduced. We consider if high-dose methylprednisolone should be recommended in children with acute metabolic crisis and encephalopathy due to HIBCHD. Since influenza A virus was the triggering cause to metabolic crisis with encephalopathy, vaccination should be considered in HIBCHD.

Resumo em Inglês:

Abstract Fabry disease (FD) is an X-linked inborn error of glycosphingolipid metabolism characterized by progressive lysosomal deposition of partially metabolized substrates within various tissues. This condition results in significant morbidity and mortality for both men and women. However, the severity and progression of the disease differ by sex due to potential factors that modulate the phenotype in women, such as X chromosome inactivation. In this study, we conducted methylation assays on peripheral blood samples from seven women diagnosed with FD and examined the correlation between these assays and the clinical severity of the disease. The results showed no correlation, underscoring the importance of selecting appropriate tissues for analysis.

Resumo em Inglês:

Abstract Niemann-Pick disease type C (NPC) disease is a lysosomal storage disorder caused by alterations in the trafficking of unesterified cholesterol due to mutations in the NPC1 and NPC2 genes. Its manifestations can be visceral, neurological, and psychiatric. This study conducts a retrospective review to assess the clinical, laboratory, molecular, and imaging features of a cohort of Brazilian patients with NPC. Eleven cases were included, 6 females and 5 males, aged between 3 and 32 years. Three cases corresponded to the early infantile form, three to the late infantile form, four to the juvenile, and one to the adult form. The most frequent symptoms were splenomegaly (10/11), hepatomegaly (8/11), vertical supranuclear gaze palsy (11/11), ataxia (10/11), dysarthria (10/11), dysphagia (10/11), spasticity (7/11), epilepsy (7/11), dystonia (7/11), cognitive impairment (8/11), and school delay (8/11). All patients exhibited non-specific abnormalities in brain imaging studies. Biomarker-specific tests were positive in 9 out of 11 cases. The Filipin test was "classic" in 6 cases and "variant" in 5. Mutations in NPC1 were identified in all patients, with the most prevalent variant being p.Ala1035Val (8/11). This case series highlights the p.Ala1035Val mutation in NPC1 correlates with the "classic" profile of Filipin staining.

Resumo em Inglês:

Abstract Methylmalonic acidemia (MMA) is a rare hereditary metabolic disorder caused by defects in the methylmalonyl-CoA mutase pathway, leading to toxic metabolite accumulation and severe multi-organ complications. This report presents the case of a 4-month-old Colombian female with MMA, diagnosed through whole-exome sequencing, which identified compound heterozygous pathogenic variants in the MMUT gene: c.607G>A (p.Gly203Arg) and c.1420C>T (p.Arg474Ter). Despite treatment-including a metabolic diet, L-carnitine, and hydroxocobalamin,-the patient experienced recurrent metabolic crises and ultimately succubed to multi-organ failure. This case underscores critical gaps in Colombia’s healthcare system, including the absence of universal newborn screening, limited access to specialized treatments, and significant administrative barriers that delay interventions. Expanding neonatal screening to include organic acidemias, improving access to essential medications, and establishing reference centers for metabolic diseases are crucial steps to improve outcomes for patients with rare metabolic disorders. This report highlights the urgent need for systemic changes in Colombia to address the inequities in diagnosis and treatment of rare diseases, ensuring timely intervention and comprehensive care for affected patients.

Resumo em Inglês:

Abstract Mucopolysaccharidosis IV-A (MPS IV-A) is an autosomal recessive genetic disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase, leading to the accumulation of chondroitin-6-sulfate (C6S) and keratan sulfate (KS). This is a rare disease, and, in Colombia, it is classified as an orphan disease under Resolution 023 of 2023. Notably, its incidence in Colombia is higher than that reported in other countries worldwide. Genomic analysis of the GALNS gene has identified more than 400 variants in affected individuals, enabling genotype-phenotype correlations. We report the case of a patient who was initially presented at the age of 5 with short stature, lower limb dysmetria, and genu valgum. Physical examination revealed coarse facial features, a short neck, pectus carinatum, multiple joint deformities, and ligamentous hyperlaxity. Enzymatic activity of GALNS was reported at 0.06 mmol/mL/hour, and complete sequencing of the GALNS gene was performed using next-generation sequencing (NGS) technology, identifying the homozygous variant c.239C>T (p.Ser80Leu), which is associated with MPS IV-A. A bioinformatic analysis classified this variant as pathogenic. This case underscores the importance of clinical presentation, the use of diagnostic methodologies, and confirmation through molecular and bioinformatic studies for an accurate and timely diagnosis, as well as the critical value of appropriate clinical follow-up.

Resumo em Inglês:

Abstract Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with an estimated prevalence ranging from 1 in 56,500 to 1 in 113,000 live births. While hemizygous males typically present with early-onset hyperammonemic encephalopathy, females carrying pathogenic variants in OTC exhibit highly variable phenotypes due to random X-chromosome inactivation, ranging from asymptomatic states to severe metabolic and neuropsychiatric manifestations. In many cases, diagnosis in females is delayed, especially when symptoms are misinterpreted as behavioral or psychiatric disorders, increasing the risk of irreversible neurological sequelae. This case series describes three Colombian females with genetically confirmed OTCD: two pediatric patients and one adult. In pediatric cases, metabolic decompensations were triggered by febrile viral illnesses and infections. In the adult patient, initial symptoms occurred during pregnancy and were misattributed to a primary psychiatric disorder. In all three cases, diagnosis was established only after multiple episodes of illness. All patients presented early on with protein aversion, which we consider a significant red flag to suspect metabolic disorders. This series underscores the diagnostic challenges in females heterozygous for OTC, the importance of recognizing catabolic stressors as triggers for clinical deterioration, and the need for early biochemical and molecular evaluation to prevent complications and reduce diagnostic delays.