A new metabolic disorder in human cationic amino acid transporter-2 that mimics arginase 1 deficiency in newborn screening.

PURPOSE: We report a patient with a human cationic amino acid transporter 2 (CAT-2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS). METHODS: A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy. RESULTS: A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss-of-function mutations in the SLC7A2 gene. Currently, the child receives a protein-controlled diet of 1.2 g/kg/day with protein-and amino-acid free infant formula, 30 g/day, and is asymptomatic. CONCLUSION: We identified a novel defect in human CAT-2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening.

Infantile sialidosis: natural history in a preterm infant with two new pathogenic mutations and new ocular findings.

Sialidosis is a rare lysosomal storage disease caused by an α-N-acetyl neuraminidase-1 deficiency due to mutations of the NEU1 gene (6p21). Disease severity varies among patients and is linked to the level of residual neuraminidase activity in vivo. At least 40 disease-causing mutations in the NEU1 gene have been reported. Sialidosis occurs in two main clinical variants: type I, the milder form of the disease, and type II, which is subdivided into congenital, infantile, and juvenile forms. We report the clinical, biochemical, and molecular characterization of a patient with infantile sialidosis type II. The abnormal urinary oligosaccharide profile is described for the first time. The genetic characterization of the patient showed two previously unreported missense mutations in the NEU1 gene: p.R78C (c.232C>T) and p.R290Q (c.869G>A).

Implications of the Mediterranean diet and physical exercise on the lipid profile of metabolically healthy obese women as measured by nuclear magnetic resonance spectroscopy (1H NMR).

OBJECTIVE: There is a lack of consensus when it comes to establishing the biochemical parameters that define metabolically healthy obese (MHO) subjects. Indeed, most studies do not include subjects' lipid profiles. Our objective was to characterize lipoprotein size, particle and subclass concentration using 1H NMR in MHO women after two years of weight loss with a hypocaloric Mediterranean diet and physical exercise. METHODS: 115 non-diabetic women (aged 35-55 years) with a body mass index (BMI) of 30-40 kg/m2 and ≤1 of the following criteria: blood pressure ≥135/85 mmHg, fasting plasma glucose ≥100 mg/dL, HDL cholesterol ≤50 mg/dL and triglycerides ≥150 mg/dL were included. After two years of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5%-<10% and ≥10%. Lipoprotein size, particle and subclass concentrations were measured using 1H NMR. RESULTS: The final population, after dropouts, were 67 women (age: 44.5 ±â€¯3.7 years, BMI: 36.3 ±â€¯4.7 kg/m2), of whom 23 (38.3%) lost <5%, and 22 (36.7%), lost ≥5% to <10% and ≥10% of baseline body weight, respectively. The lipid profile showed no significant changes after intervention, especially in small LDL particles or in production of HDL. The diameter of LDL and HDL particles did not change after two years of a Mediterranean diet and physical exercise. CONCLUSION: These results indicate that intensive lifestyle modification does not produce significant changes in the lipid profile of MHO women. Levels of more atherogenic or atheroprotective particles did not change after two years, despite the intervention.

Characterization of lipid profile by nuclear magnetic resonance spectroscopy (1H NMR) of metabolically healthy obese women after weight loss with Mediterranean diet and physical exercise.

Obesity is associated with an atherogenic lipid profile. No data exists on lipoprotein particle profiles in metabolically healthy obese (MHO) individuals. Our aim is to characterize lipoprotein size, particle, and subclass concentrations in MHO women after 3 months of weight loss through dietary restriction and physical exercise.A total of 115 nondiabetic women (aged 35-55 years) with a body mass index (BMI) of 30 to 40 kg/m and ≤1 of the following criteria: blood pressure ≤135/85 mm Hg, fasting plasma glucose ≤100 mg/dL, HDL-cholesterol ≤50 mg/dL, and triglycerides ≤150 mg/dL were included. After 3 months of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5% to <10%, and ≥10%. Lipoprotein size, particle, and subclass concentrations were measured using H NMR.The final sample, after dropouts, comprised 104 women (age: 44.4 ±â€Š3.7 years, BMI: 36.3 ±â€Š4.7 kg/m), of whom 47 (45.2%), 27 (26%), and 30 (28.8%) lost <5%, ≥5% to <10%, and ≥10% of baseline body weight, respectively. All participants experienced significant weight loss and decreases in BMI. The lipid profiles showed an increase in small, medium, and large very low density lipoprotein (VLDL) particles in all groups of study with the exception of small VLDL particles in women with ≥10% of weight loss, in which it decreased. The number of VLDL particles decreased in women who had ≥10% weight loss. On the other hand, we detected a decrease in all low density lipoprotein (cLDL) and high density lipoprotein (cHDL) concentrations.These results indicate that intensive lifestyle modification alters lipid profiles. In particular, it decreases small LDL and HDL particle numbers and does not increase medium or large HDL particles numbers.