Classical homocystinuria, is it safe to exercise?

Abstract

Background Cystationine β-synthase (CBS) deficiency is a genetic disorder characterized by severe hyperhomocysteinemia and thrombotic complications. In healthy individuals, physical exercise may result in a transient increase in plasma total homocysteine (tHcy) raising the possibility that exercise might be detrimental in CBS deficiency. Our main objective was to determine plasma tHcy kinetics in response to physical exercise in homocystinuria patients. Methods Six adult patients (2 males, 4 females) with homocystinuria and 6 age- and gender-matched controls completed a 30-min aerobic exercise of moderate-intensity with fixed power output (50 W for women and 100 W for men). Blood samples were drawn before, immediately, 180 min and 24 h after exercise. tHcy levels were determined by standard procedures; substrate oxidation and energy expenditure were measured using indirect calorimetry. Results Acute exercise was well tolerated and safe in patients and controls. During the exercise bout, heart rate and energy expenditure increased equally in both groups. tHcy levels were higher in patients compared to controls at all time points ( p < 0.05). There was no significant effect of exercise on tHcy levels at any time point ( p = 0.36). Although two patients with partial pyridoxine responsiveness presented higher homocysteine responses, their highest value remained below 55 μmol/l. Conclusions Overall metabolic responses to acute exercise were similar between homocystinuria patients and controls; specifically, exercise did not significantly change tHcy concentrations. Moderate physical exercise was well tolerated without any adverse event in our cohort of patients. Further studies are needed to identify the effects of different intensities and modes of exercise in larger cohorts of CBS patients with different levels of pyridoxine responsiveness.

A new case of sodium‐dependent multivitamin transporter defect occurring as a life‐threatening condition responsive to early vitamin supplementation and literature review

“…(2019) reported a mild decrease in biotinidase activity that remained normal in our patient. These observations support ours and we propose that the persistence of elevated and isolated urinary levels of 3‐HIA could be a red flag suggesting testing for inborn errors of metabolism as biotinidase, holocarboxylase synthetase, or SMVT deficiencies (Tankeu et al., 2023).…”

“…(2022) went on to describe another patient who presented an acute metabolic decompensation with lactic acidosis (pH 7.1, lactate 3 mmol/L) and hypoglycemia (1.7 mmol/L). Elevated blood lactate levels are observed in case of impaired metabolization of pyruvate as reported in biotin deficiency (Hauth et al., 2022; Tankeu et al., 2023). Metabolic assessments also showed slightly elevated urinary 3‐HIA associated to elevated plasma C5‐OH‐carnitine, which is classically seen in biotinidase deficiency (Hauth et al., 2022; Tankeu et al., 2023).…”

“…Elevated blood lactate levels are observed in case of impaired metabolization of pyruvate as reported in biotin deficiency (Hauth et al., 2022; Tankeu et al., 2023). Metabolic assessments also showed slightly elevated urinary 3‐HIA associated to elevated plasma C5‐OH‐carnitine, which is classically seen in biotinidase deficiency (Hauth et al., 2022; Tankeu et al., 2023). Urinary excretion of 3‐HIA has been demonstrated to be an early and sensitive indicator of marginal biotin deficiency (Mock et al., 2011).…”

“…Specific treatment regimens are currently based on the regimen published by Subramanian et al. (2017) and the regimen used in biotinidase deficiency (Saleem & Soos, 2023; Tankeu et al., 2023). Holling et al.…”