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An association between sulfur amino acids (methionine, cysteine, homocysteine and taurine) and lipid metabolism has been described in several experimental and population-based studies. Changes in the metabolism of these amino acids influence serum lipoprotein concentrations, although the underlying mechanisms are still poorly understood. However, recent evidence has suggested that the enzyme stearoyl-CoA desaturase-1 (SCD-1) may be the link between these two metabolic pathways. SCD-1 is a key enzyme for the synthesis of monounsaturated fatty acids. Its main substrates C16:0 and C18:0 and products palmitoleic acid (C16:1) and oleic acid (C18:1) are the most abundant fatty acids in triglycerides, cholesterol esters and membrane phospholipids. A significant suppression of SCD-1 has been observed in several animal models with disrupted sulfur amino acid metabolism, and the activity of SCD-1 is also associated with the levels of these amino acids in humans. This enzyme also appears to be involved in the etiology of metabolic syndromes because its suppression results in decreased fat deposits (regardless of food intake), improved insulin sensitivity and higher basal energy expenditure. Interestingly, this anti-obesogenic phenotype has also been described in humans and animals with sulfur amino acid disorders, which is consistent with the hypothesis that SCD-1 activity is influenced by these amino acids, in particularly cysteine, which is a strong and independent predictor of SCD-1 activity and fat storage. In this narrative review, we discuss the evidence linking sulfur amino acids, SCD-1 and lipid metabolism.

BackgroundClassical homocystinuria (HCU) is a monogenic disease caused by the deficient activity of cystathionine β‐synthase (CβS). The objective of this study was to identify the CBS mutations in Brazilian patients with HCU.Methods gDNA samples were obtained for 35 patients (30 families) with biochemically confirmed diagnosis of HCU. All exons and exon‐intron boundaries of CBS gene were sequenced. Gene expression analysis by qRT‐PCR was performed in six patients. Novel missense point mutations were expressed in E. coli by site‐directed mutagenesis.ResultsParental consanguinity was reported in 16 families, and pyridoxine responsiveness in five (15%) patients. Among individuals from the same family, all presented the same phenotype. Both pathogenic mutations were identified in 29/30 patients. Twenty‐one different mutations were detected in nine exons and three introns; being six common mutations. Most prevalent were p.Ile278Thr (18.2%), p.Trp323Ter (11.3%), p.Thr191Met (11.3%), and c.828+1G>A (11.3%). Eight novel mutations were found [c.2T>C, c.209+1delG, c.284T>C, c.329A>T, c.444delG, c.864_868delGAG c.989_991delAGG, and c.1223+5G>T]. Enzyme activity in E. coli‐expressed mutations was 1.5% for c.329A>T and 17.5% for c.284T>C. qRT‐PCR analysis revealed reduced gene expression in all evaluated genotypes: [c.209+1delG; c.572C>T]; [c.2T>C; c.828+1G>A]; [c.828+1G>A; c.1126G>A]; [c.833T>C; c.989_991delAGG]; [c.1058C>T; c.146C>T]; and [c.444delG; c.444delG]. The expected phenotype according to the genotype (pyridoxine responsiveness) matched in all cases.ConclusionsMost patients studied were pyridoxine nonresponsive and presented early manifestations, suggesting severe phenotypes. Many private mutations were observed, but the four most prevalent mutations together accounted for over 50% of mutated alleles. A good genotype–phenotype relationship was observed within families and for the four most common mutations.

These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism.

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.

Background: In phenylketonuria (PKU), only a limited range of natural foods, such as fruits, vegetables, oils and sugars, can be consumed without restrictions. The present study aimed to study if food neophobia (i.e. an unwillingness to eat novel food) occurs in patients with PKU and to compare in non-PKU healthy controls and to identify any associated factors. Methods: This cross-sectional case-control study used a convenience sampling strategy to recruit patients diagnosed with PKU and healthy controls matched by gender and age. Patients and controls were invited to complete the food neophobia scale (FNS) questionnaire, and clinical and treatment data were collected through a review of medical records. Results: Twenty-five patients (mean age 19.3 ± 4.7 years, 13 women) with PKU and 25 controls (mean age 19.9 ± 4.9 years; P = 0.676, 13 women) were evaluated. The mean age of treatment onset in patients with PKU was 52.8 ± 29.7 days. The mean phenylalanine (Phe) level in the 12-month preceding neophobia study was 710.5 ± 346 µmol/L. The mean FNS score of patients with PKU was significantly higher (47.2 ± 9.7) than controls (29.4 ± 12.5, P < 0.001). Food neophobia was associated more with male gender (P = 0.039). Conclusions: Food neophobia is frequent in patients with PKU. It does not appear to be associated with female gender, with Phe levels and not just in children.

Genetic homocystinurias are a group of inborn errors of metabolism that result in the massive excretion of homocysteine (Hcy) in the urine due to Hcy accumulation in the body, usually causing neurological and cardiovascular complications. The three most frequent causes are classical homocystinuria [deficiency of cystathionine beta-synthase (CBS)], methylmalonic aciduria with homocystinuria, cblC type (cblC deficiency) and severe methylenetetrahydrofolate reductase (MTHFR) deficiency. In this review, we highlight the similarities and differences among these disorders. Briefly, their joint manifestation is the accumulation of tHcy, however, the other sulfur amino acids show various and even invers profiles. Vascular disease, developmental delay and seizures are found in all homocystinurias, nevertheless, the complications of CNS differ in a wide variety of presentations and severities and are apparently less pronounced in CBS deficiency. Moreover, patients with remethylation defects typically do not present ectopia lentis and bone disturbances, tall stature and osteoporosis. Whereas hematological alterations, such as megaloblastic anemia, thrombocytopenia neutropenia and life-threatening microangiopathy, are specific findings of cblC deficiency.