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.

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9–20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ −2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ −2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disease caused by variants in the GBE1 gene, which encodes the glycogen branching enzyme (GBE). GSD IV accounts for approximately 3% of all GSD. The phenotype of GSD IV ranges from neonatal death to mild adult-onset disease with variable hepatic, muscular, neurologic, dermatologic, and cardiac involvement. There is a paucity of literature and clinical and dietary management in GSD IV, and liver transplantation (LT) is described to correct the primary hepatic enzyme defect. Objectives: We herein describe five cases of patients with GSD IV with different ages of onset and outcomes as well as a novel GBE1 variant. Methods: This is a descriptive case series of patients receiving care for GSD IV at Reference Centers for Rare Diseases in Brazil and in the United States of America. Patients were selected based on confirmatory GBE1 genotypes performed after strong clinical suspicion. Results: Pt #1 is a Latin male with the chief complaints of hepatosplenomegaly, failure to thrive, and elevated liver enzymes starting at the age of 5 months. Before LT at the age of two, empirical treatment with corn starch (CS) and high protein therapy was performed with subjective improvement in his overall disposition and liver size. Pt #2 is a 30-month-old Afro-American descent patient with the chief complaints of failure to gain adequate weight, hypotonia, and hepatosplenomegaly at the age of 15 months. Treatment with CS was initiated without overall improvement of the symptoms. Pt #3.1 is a female Latin patient, sister to pt #3.2, with onset of symptoms at the age of 3 months with bloody diarrhea, abdominal distention, and splenomegaly. There was no attempt of treatment with CS. Pt #4 is an 8-year-old male patient of European descent who had his initial evaluation at 12 months, which was remarkable for hepatosplenomegaly, elevated ALT and AST levels, and a moderate dilatation of the left ventricle with normal systolic function that improved after LT. Pt #1, #3.2 and #4 presented with high levels of chitotriosidase. Pt #2 was found to have the novel variant c.826G > C p.(Ala276Pro). Conclusions: GSD IV is a rare disease with different ages of presentation and different cardiac phenotypes, which is associated with high levels of chitotriosidase. Attempts of dietary intervention with CS did not show a clear improvement in our case series.

Patients with phenylketonuria (PKU) who retain residual phenylalanine hydroxylase (PAH) activity may benefit from sapropterin dihydrochloride (sapropterin) administration. Objective: To characterize sapropterin responsiveness in patients with PKU and investigate the impact of natural fluctuations in phenylalanine (PHE) levels and variations in PHE intake on sapropterin responsiveness. Methods: Retrospective chart review study. Patients with PKU who underwent the 24 h responsiveness test, including correction for natural PHE fluctuations, were included. Responders were defined as those who exhibited a >30% reduction in PHE levels within 8 h and/or 24 h after intake of 20 mg/kg sapropterin, correcting for the natural fluctuation in plasma PHE levels on day 1. Patients with a 28–30% reduction in PHE were considered sapropterin-responsive only if they had a concordant genotype. Results: Fifteen patients completed the test; however, three were excluded due to non-compliance. Additionally, one patient with mild PKU exhibited a borderline response, but the genotype agreement could not be assessed, rendering the test inconclusive. The rate of responsiveness could be assessed for eleven patients (six mild and five classical PKU). Among the patients with mild PKU, four were classified as responders: three at both 8 h and 24 h (reduction in plasma PHE: −75.9 ± 20.2% at 8 h and −75.7 ± 37.0% at 24 h) and one at 8 h only (reduction in plasma PHE: −28.7%). All patients with classic PKU (n = 5) were non-responders. Conclusions: A 24 h sapropterin responsiveness test incorporating correction for natural fluctuations in PHE levels identified a proportion of sapropterin-responsive patients with mild PKU similar to that described in the literature. PHE consumption should be objectively controlled during the protocol to avoid bias in determining responsiveness.

Background/Objectives: Hepatic glycogen storage diseases (GSDs) are inherited metabolic disorders that affect glycogen synthesis or breakdown, primarily involving the liver and muscles. Treatment typically consists of strict dietary management, including the consumption of uncooked cornstarch. However, there is limited research on feeding challenges and the associated stress experienced by parents of children with GSDs. This study aims to assess feeding difficulties in children with GSDs and the level of parental stress. Methods: A total of 29 caregivers of children aged 6 months to <7 years participated. Feeding difficulties were evaluated using the Brazilian Infant Feeding Scale (Escala Brasileira de Alimentação Infantil—EBAI), while parental stress was measured using the Parental Stress Scale (Escala de Estresse Parental—EEPa). Data were collected in 2020, and the study was approved by the ethics committee. Results: The majority of the children were male (19/10), with a mean age of 47.75 months and an average age of diagnosis of 8.39 months. GSD type Ia (n = 15) and type Ib (n = 5) were the most prevalent, followed by types III and IX (n = 2). Among the participants, 22 out of 29 (76%) reported feeding difficulties, categorized as mild (n = 7, 24%), moderate (n = 7, 24%), and severe (n = 8, 28%). EBAI scores were higher in female patients and in those who did not eat meals with their family. Only one caregiver exhibited high levels of parental stress, as measured by the EEPA scale. No significant correlation was found between feeding difficulties and parental stress. Conclusions: The findings confirm a high prevalence of feeding issues in children with GSDs, which significantly affects caregivers’ quality of life. Although no significant link between feeding difficulties and parental stress was identified, further research is needed to improve GSD management and provide better support for caregivers.

Aim: To evaluate the status of the nutritional management of diet-treated IEM in Brazil from the perspectives of healthcare professionals, patients, and families. Methods: Data were collected through two nationwide digital questionnaires administered to healthcare professionals involved in dietary management (n = 37) and to patients and caregivers (n = 278), addressing professional training, workload, access to resources, treatment adherence, and socioeconomic factors. Results: Healthcare professionals from 20 out of the 26 Brazilian states participated, most of them female (81%) and dietitians (81%). Although more than half had over 10 years of experience, 59% considered their training insufficient to work with IEM. Only 19% reported exclusive dedication to the field, and 54% were the sole professional responsible for dietary prescriptions at their center. Weekly workload dedicated to IEM varied widely. Among the patients and families, phenylketonuria (60.4%) and glycogen storage disease (25.9%) were the most frequent conditions. Higher educational level and longer time since diagnosis were associated with a better understanding of dietary management (p < 0.05). Among patients on protein-restricted diets, most reported regular use of protein substitutes, although 92% reported poor palatability and 36% reported supply problems. Access to special low-protein foods was limited, and over half of the families reported some level of food insecurity. Conclusions: Significant systemic, logistical, and socioeconomic barriers to optimal dietary management of IEM persist in Brazil, highlighting the need for strengthened public policies, professional training, and equitable access to dietary resources.