Resumo em Inglês:

Abstract Phenylketonuria (PKU) is an autosomal recessive defect affecting the metabolic pathway of phenylalanine (Phe), causing hyperphenylalaninemia and neurotoxicity. Diagnosis must occur in the neonatal period and treatment should begin as early as possible. Evidence implies that treatment adherence declines as age advances. The aim was to describe the diet of a subgroup of Chilean adults with PKU currently in follow-up. Fifty-three subjects (49% women) followed up between January 2021 to April 2023 were considered. The concentration of Phe (PheC) in dried blood spots measured by fluorometry and 24-hour dietary recalls were analyzed. The median PheC of the sample was 438µmol/L (interquartile range(IQR):351-585µmol/L). A protein intake of 1.35±0.3 gr/Kg/d was observed of which 87% came from the protein substitute without Phe. Participants had a median Phe intake of 459mg/d (IQR:327-976) and 13.1g/d of fiber intake. Most participants, 51% and 92% reported consuming fruits and vegetables, respectively, and 32% consumed Low-Protein foods. Regarding micronutrients, all participants exceeded 90% adequacy according to recommendations. For vitamin-D and vitamin-B12, 100% is provided by the protein substitute. According to our results, it is mandatory to establish transition programs toward adulthood, to constantly maintain good metabolic control, and to adapt diet therapy to their new lifestyle.

Resumo em Inglês:

Abstract Mucopolysaccharidosis type IH (MPS IH) is caused by homozygous IDUA gene pathogenic variants. This results in deficiency of the enzyme α-L-iduronidase (IDUA), which is necessary for the degradation of glycosaminoglycans (GAGs). This study outlines the long-term outcomes in adult Irish patients affected with MPS IH, who were followed up for mean 28 years post Haematopoietic Stem Cell Transplantation. Nineteen adult MPS IH patients underwent HSCT in childhood. The participant cohort represents 6 families. Among the 13 patients with Irish Traveller ethnicity, 6 patients were either siblings or first cousins. All these related patients were homozygous for p. Trp402Ter (W402X). Mean age at the first transplantation was 8 months (range 3-21). Five patients had undergone a second transplantation (n=5, 26%) in childhood, due to graft failure. None of the patients had a cardiac valve surgery at the time of the study. 14/19 patients had mild to moderate aortic or mitral valve insufficiency or stenosis. 3/19 patients used non-invasive ventilation at night. Two patients had tracheostomy in situ. Both sensorineural as well as conductive hearing defects. No corneal clouding post corneal transplantation (n=8) was observed. Six patients attended regular secondary school. Multidisciplinary follow-up is needed to address the disease specific complications in adulthood.

Resumo em Inglês:

Abstract Fabry disease is a rare X-linked lysosomal storage disorder that causes progressive cellular accumulation of glycosphingolipids, leading to various end-organ manifestations such as chronic kidney disease and cardiomyopathy. Currently, troponin is the preferred biomarker to identify acute coronary syndromes and cardiac inflammation/myocarditis, as well as monitor myocardial damage. Macrotroponin is an immunoglobulin G-troponin bound complex with reduced clearance due to its higher molecular weight. This can cause false elevations in troponin, in the absence of myocardial damage, which has been reported in up to 5% of patients presenting to emergency departments in Australia. In this case series, we report on ten Fabry patients in whom macrotroponin was demonstrated after precipitation with polyethylene glycol (PEG). Of the 47 routine clinical samples of Fabry patients that were analysed, troponin was demonstrated to be elevated in 15 samples (32%), and ten of these demonstrated macrotroponin (21% of total, 67% of elevated troponin). This case series highlights the need to consider the possibility of macrotroponin in Fabry patients with elevated troponin. This relatively high prevalence raises the questions of whether Fabry patients are intrinsically more predisposed to macrotroponin and how this influences clinical management, which warrants further research.

Resumo em Inglês:

Abstract Hepatic glycogen storage diseases (GSD) are characterized by recurrent episodes of hypoglycemia, and anemia has been recognized as a frequent complication of these disorders. This was a convenience cross-sectional study to evaluate hepcidin and IL-6 concentrations in patients with hepatic GSD and their association with anemia and other parameters of iron metabolism. Levels of hepcidin, IL-6, and markers of iron metabolism were measured in 32 patients receiving uncooked cornstarch therapy for GSD (GSD Ia= 18; Ib= 7; III= 3; IXa= 3; IXb= 1; median age 9.5 years). IL-6 concentrations were compared to those of 8 individuals heterozygous for GSD. Nine patients were anemic and five patients had hepatic adenomas. IL-6 levels were higher in patients than in heterozygotes. Eight patients had hyperferritinemia, and one had elevated transferrin saturation as well. Hepcidin correlated positively with ferritin levels. IL-6 correlated with hemoglobin, iron, transferrin, and transferrin saturation. There was no correlation between hepcidin and IL-6 levels. Patients with GSD Ib had the highest IL-6 levels. Anemia is a common finding in hepatic GSD, especially in GSD Ib, the type of GSD associated with the highest IL-6 levels. These findings suggest that inflammation is strongly associated with development of anemia in GSD Ib.

Resumo em Inglês:

Abstract Introduction: The advent of newborn screening across India has led to an increase in the early diagnosis of inborn errors of metabolisms (IEMs). Aminoacidopathies, the group of inherited disorders of amino acid metabolisms are of particular important because of the ease of early diagnosis and the availability of effective treatment options. Unfortunately, the biological reference intervals for amino acids vary widely between different ethnic groups and geographical locations, thereby necessitating the need to establish a population specific reference interval for optimal diagnosis. Aims and objectives: Establishment of the biological reference interval for all amino acids in the Dried Blood Spots (DBS) of term neonates belonging to coastal Karnataka using High Performance Liquid Chromatography. Methods: Heel prick blood samples were collected from 175 healthy, term neonates on a filter paper. After safe transport to the laboratory, the amino acids were extracted using an appropriate solution, derivatized, and analyzed using high performance liquid chromatography. Mean, standard deviation, and 95% confidence interval of the mean were used to establish the reference interval. Students T-test was used to compare the differences in amino acids levels among different groups. Conclusions: The biological reference intervals obtained in this study was found to have significant variations from studies conducted elsewhere in the world. This puts into perspective the need to establish a population specific reference interval for these parameters to avoid potential misdiagnosis. This reference interval may also be adopted by other labs catering to new-born screening in the same geographical area.

Resumo em Inglês:

Abstract Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder, characterized by alterations in the catabolism of chylomicrons and by increased levels of plasma triglycerides. It has been shown that about 60-90% of FCS patients have biallelic mutations in the LPL gene and the remaining patients have mutations in genes encoding proteins closely related to LPL function. The objective of this manuscript is to illustrate the different clinical scenarios of FCS presentation, and to guide practitioners on the usefulness of genetic tests in each of them. To this end, several published papers about recommendations for the diagnosis of FCS are discussed briefly, in addition to the presentation of several hypothetical cases, highlighting different clinical presentations and possible associated genetic findings. These cases illustrate the multiplicity of potential aspects of family history, clinical manifestations, biochemical parameters, and patterns of genetic variants found in genomic analyses of FCS.

Resumo em Inglês:

Abstract Medium chain acyl-coA dehydrogenase deficiency (MCADD), the most common fatty acid oxidation disorder, has been regarded as a relatively benign condition with low risk of mortality in patients with a known diagnosis, if adequate caloric intake is met. However, inadequate energy provision, as occurs in eating disorders, significantly amplifies the risk of metabolic decompensation. This case series describes four patients with MCADD and a concomitant eating disorder and aims to raise awareness of the potentially under-recognised coexistence of these conditions. All patients were female with signs of disordered eating in adolescence and young adulthood though latency in diagnosis was apparent. Three of the patients had low body mass index (BMI) and the other was overweight. Metabolic decompensation and hospitalisation occurred in three of four patients secondary to extreme risk-taking behaviour with caloric restriction. The coexistence of MCADD and eating disorders is of significant concern, placing the patient at substantial risk of decompensation in an otherwise relatively stable metabolic condition. Awareness of disordered eating in this population is paramount, as early recognition of signs and symptoms of eating disorders in the MCADD population may facilitate prompt intervention and avoidance of morbidity and potential mortality.