Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, from 33 unrelated families, were analyzed through next-generation sequencing in the Ion Torrent PGM™ platform. Phenotype–genotype correlations were made based on the BioPKU database. Three patients required additional Sanger sequencing analyses. Twenty-six different pathogenic variants were identified. The most frequent variants were c.1315+1G>A (n = 8/66), c.473G>A (n = 6/66), and c.1162G>A (n = 6/66). One novel variant, c.524C>G (p.Pro175Arg), was found in one allele and was predicted as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) criteria. The molecular modeling of p.Pro175Arg indicated that this substitution can affect monomers binding in the PAH tetramer, which could lead to a change in the stability and activity of this enzyme. Next-generation sequencing was a fast and effective method for diagnosing PKU and is useful for patient phenotype prediction and genetic counseling.

Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

Congenital Hypothyroidism affects between 1:3000 and 1:4000 newborn infants in iodine-sufficient regions. Some studies have shown that mutations and polymorphisms in the TSH receptor gene are responsible for this disease. In the present study, mutations of exon 10 of the TSH receptor gene were investigated in Congenital Hypothyroidism patients. In the present study a sample of 90 Brazilian patients with primary congenital hypothyroidism was analyzed. Genomic DNA was isolated from peripheric blood samples. Exon 10 of the TSH receptor gene was amplified by PCR, and amplicons were automatically sequenced. Three nucleotide alterations were identified: c.1377G>A (A459A), c.1935G>A (L645L), and c.2181C>G (D727E). A459A polymorphism was also described previously in patients with thyroid cancer. The nucleotide alteration L645L was found in a single patient. This is the first time the L645L mutation has been described. D727E polymorphism showed high frequency (allele frequency 10%) in present study when compared to others reports.

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.

To analyze the impact of the CHILD-2 diet on the lipid profile of Brazilian children and adolescents with dyslipidemia. This is a quasi-experimental study, where 149 participants (5–17 years) with mild-to-moderate hypercholesterolemia were divided into two groups (GI: low or normal weight; n = 58 and GII: overweight; n = 91). Both groups underwent the CHILD-2 diet, characterized by 25–30% total fat and less than 7% of low-saturated fat (SF) for 6 months. Changes from baseline in the lipid profile, including Total cholesterol (TC), LDL-C, triacylglycerols and glucose concentrations, dietary and anthropometric data were examined at 3 and 6 months. Longitudinal analyses were performed using linear mixed-effects models in SAS. Serum LDL-C concentrations reduced over time compared with baseline (Δ = −5.1 mg/dL; p < 0.01), with no difference between groups (p = 0.35). TC concentrations decreased by −2.0 mg/dL (p < 0.01); but no difference was observed between groups. We found no significant changes in body mass index/age Z scores after a dietary intervention compared with baseline in both groups (p = 0.94). Despite the modest reduction, our findings confirm that children with dyslipidemia can benefit from the CHILD-2 diet combined with a healthy lifestyle.