This study aimed to describe the current practices in the diagnosis and dietary management of phenylketonuria (PKU) in Latin America, as well as the main barriers to treatment. We developed a 44-item online survey aimed at health professionals. After a pilot test, the final version was sent to 25 practitioners working with inborn errors of metabolism (IEM) in 14 countries. Our results include 22 centers in 13 countries. Most countries (12/13) screened newborns for PKU. Phenylalanine (Phe) targets at different ages were very heterogeneous among centers, with greater consistency at the 0–1 year age group (14/22 sought 120–240 µmol/L) and the lowest at >12 years (10 targets reported). Most countries had only unflavored powdered amino acid substitutes (10/13) and did not have low-protein foods (8/13). Only 3/13 countries had regional databases of the Phe content of foods, and only 4/22 centers had nutrient analysis software. The perceived obstacles to treatment were: low purchasing power (62%), limited/insufficient availability of low-protein foods (60%), poor adherence, and lack of technical resources to manage the diet (50% each). We observed a heterogeneous scenario in the dietary management of PKU, and most countries experienced a lack of dietary resources for both patients and health professionals.

There are concerns about muscle and bone health in patients with Phenylketonuria (PKU). Our aim was to compare muscle mass, function, and bone health among young adults with PKU who maintained or suspended dietary treatment. Methods: Three groups were considered—PKU-1: 10 patients who used a protein substitute (PS) without phenylalanine (Phe); PKU-2: 14 patients who used the PS without Phe until eighteen years old and then practiced mostly a vegan diet; and 24 matched healthy controls. A 24 h recall survey, blood parameters, body composition and bone mineral density through DEXA, rectus femoris thickness by ultrasound, hand grip strength, submaximal exercise test, and walking speed were assessed. Results: PKU-1 patients had lower hand grip strength than their matched controls, but no other differences. Compared to controls, the PKU-2 group had lower fat-free mass (p = 0.01), less spine and femoral bone mineral density (p = 0.04 and p < 0.01, respectively), and peak workload on the incremental test (p = 0.03). When comparing PKU groups, blood Phe levels were significantly lower in the PKU-1 group (p = 0.02). Conclusions: Among PKU patients, abandoning the dietary treatment and maintaining high blood Phe concentrations could be deleterious for muscles and bones. However, we cannot discard other causes of bone and muscle damage in these patients.

Since neonatal screening and early nutritional treatment began, it has been possible to reverse the neurological damage that phenylketonuria (PKU) causes. Scientific evidence gathered over more than 50 years on the monitoring of individuals with PKU indicates that a phenylalanine level of about 6 mg/dL (360 µmol/L) is ideal and points to the necessity of starting a long-term phenylalanine-restricted diet in which blood phenylalanine level should stay between 2 and 6 mg/dL (120-360 µmol/L). This article aims to establish the general basis for proper monitoring of people with PKU and provide a useful tool for clinicians overseeing treatment. We hope to establish similar criteria throughout Latin America and create a uniform protocol in order to have comparative monitoring results for the region.

Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched‐chain α‐keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients.Methods: This manuscript describes a cross‐sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.Results: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients.Conclusion: If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype‐phenotype relationships more efficiently.

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism where high phenylalanine (Phe) concentrations cause irreversible intellectual disability that can be prevented by newborn screening and early treatment. Evidence suggests that PKU subjects not adherent to treatment could be at risk of insulin resistance (IR). We studied how Phe concentrations (PheCs) relate to IR using machine learning (ML) and derived potential biomarkers. In our cross-sectional study, we analyzed subjects with neonatal diagnoses of PKU, grouped as follows: 10 subjects who adhered to treatment (G1); 14 subjects who suspended treatment (G2); and 24 control subjects (G3). We analyzed plasma biochemical variables, as well as profiles of amino acids and acylcarnitines in dried blood spots (DBSs). Higher PheCs and plasma insulin levels were observed in the G2 group compared to the other groups. Additionally, a positive correlation between the PheCs and homeostatic measurement assessments (HOMA-IRs) was found, as well as a negative correlation between the HOMA-Sensitivity (%) and quantitative insulin sensitivity check index (QUICKI) scores. An ML model was then trained to predict abnormal HOMA-IRs using the panel of metabolites measured from DBSs. Notably, ranking the features’ importance placed PheCs as the second most important feature after BMI for predicting abnormal HOMA-IRs. Our results indicate that low adherence to PKU treatment could affect insulin signaling, decrease glucose utilization, and lead to IR.