Sara Parolisi

Background/Objectives: Hereditary fructose intolerance (HFI) is a rare autosomal recessive metabolic disorder caused by variants in the ALDOB gene, resulting in aldolase B deficiency. Symptoms occur after the ingestion of fructose, sucrose, or sorbitol, leading to metabolic toxicity. Management is exclusively dietary, but clinical practice remains highly variable. This survey aimed to investigate current Italian dietary management practices for patients with HFI. Methods: A cross-sectional centre-level survey was conducted using a 29-item questionnaire distributed to metabolic dietitians within the Italian Society for the Study of Inherited Metabolic Diseases network between April and May 2026. Results: Data from 27 dietitians across 15 Italian inherited metabolic disease centres were analysed. Over half of the centres (53.3%) provided care for both paediatric and adult patients, and all centres (100%) supplied structured educational materials for the fructose-, sucrose-, and sorbitol-restricted diet. Marked heterogeneity was observed in dietary practices, particularly in the classification of sugars and sweeteners, recommendations for cereal-based products, and fibre supplementation strategies. Cereal-based dietary guidance was provided by 10/15 centres (66.7%), ranging from no specific recommendations (5/15, 33.3%) to a preference for refined grains (7/15, 46.7%) or fibre-based restrictions (2/15, 13.3%). With regard to sugars and sweeteners, consensus was observed only for maltitol and sorbitol, which were classified as prohibited by all centres (15/15, 100%). Mannitol and isomalt were prohibited in 14/15 centres (93.3%). All other compounds showed variable recommendations across centres, including xylitol (prohibited 46.7%, permitted 40.0%), erythritol (permitted 60.0%), and sucralose (prohibited 33.3%, permitted 20.0%, restricted 20.0%, unspecified 26.7%). Vitamin C (100%) and folic acid (86.6%) were the most commonly prescribed supplements. One-third (33%) of the centres required the use of fibre supplements or osmotic laxatives to manage chronic constipation, with wide variability in the specific type of fibre recommended. Conclusions: These findings highlight substantial heterogeneity in dietary management of HFI across specialised Italian centres and support the development of evidence-based, standardised nutritional guidelines to improve the consistency of care, nutritional adequacy, and patient outcomes.

Background/Objectives: Phenylketonuria (PKU) is an inherited metabolic disorder requiring early and lifelong dietary management through a low-phenylalanine (Phe) diet supplemented with Phe-free protein substitutes (PS). Recently developed slow-release PS formulations aim to mimic natural protein absorption, enhancing metabolic stability and tolerability. The PREMP study (effect of Protein RElease on the Microbiota composition and function in Phenylketonuric subjects) assessed the effects of a slow-release, Phe-free PS on gut microbiota composition and metabolic parameters in patients with PKU. Methods: Patients aged ≥6 years with PKU were enrolled from two Italian centers (Milan and Naples). Participants replaced ≥50% of their usual protein equivalent (P.Eq.) intake from Phe-free PS with a slow-release PS for 4 months. Clinical, biochemical, and nutritional assessments were performed at baseline and post-intervention. Gut microbiota composition was analyzed by 16S rRNA gene sequencing, and fecal fatty acids were quantified by gas chromatography–mass spectrometry. Results: Thirteen patients (median age 17 years) completed the intervention, replacing on average 78% of their usual P.Eq. intake with the slow-release formulation. Plasma phenylalanine and tyrosine levels remained stable, while fasting insulin (p = 0.0185) and HOMA-IR (p = 0.0099) significantly decreased, indicating improved insulin sensitivity. Anthropometric and dietary parameters showed no significant changes. Gut microbiota diversity remained stable, with modest increases in microbial richness and beneficial genera such as Bacteroides, Bifidobacterium, and Gemmiger, while Hafnia, Anaerostipes and Romboutsia decreased. Fecal butyrate and other fatty acids showed slight, non-significant increases. Conclusions: The slow-release PS was safe, well-tolerated, and improved insulin sensitivity without affecting amino acid or nutritional status. Microbial changes suggest potential benefits for gut health, warranting confirmation in larger, long-term studies.