Beneficial Effects of Ketogenic Diet on Phosphofructokinase Deficiency (Glycogen Storage Disease Type VII)

Background: A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII.Patient and Methods: A ketogenic diet (KD) intervention implemented as a modified Atkins diet was established for one patient with PFKM deficiency, with a low late lactate response and very high ammonia levels associated with exercise. We recorded the KD intervention for a total of 5 years with clinical and physiotherapeutic evaluations and regular laboratory parameters. Cardiopulmonary exercise testing, including breath gas analysis and venous lactate and ammonia measurements, was performed before KD and at 3, 8 months and 5 years after initiation of KD.Results: During the 5 years on KD, the patient's muscle symptoms had alleviated and exercise tolerance had improved. In exercise testing, venous ammonia had normalized, the lactate profile remained similar, but oxygen uptake and mechanical efficiency had increased and parameters showing ventilation had improved.Conclusions: This study is the first to show a long-term effect of KD in GSD VII with an alleviation of muscle symptoms, beneficial effects on breathing, and improvement in exercise performance and oxygen uptake. Based on these findings, KD can be recommended under medical and nutritional supervision for selected patients with GSD VII, although further research of this rare disease is warranted.Peer reviewe

Converting FENO by different flows to standard flow FENO

In clinical practice, assessment of expiratory nitric oxide (F-ENO) may reveal eosinophilic airway inflammation in asthmatic and other pulmonary diseases. Currently, measuring of F-ENO is standardized to exhaled flow level of 50 ml s(-1), since the expiratory flow rate affects the F-ENO results. To enable the comparison of F-ENO measured with different expiratory flows, we firstly aimed to establish a conversion model to estimate F-ENO at the standard flow level, and secondly, validate it in five external populations. F-ENO measurements were obtained from 30 volunteers (mixed adult population) at the following multiple expiratory flow rates: 50, 30, 100 and 300 ml s(-1), after different mouthwash settings, and a conversion model was developed. We tested the conversion model in five populations: healthy adults, healthy children, and patients with COPD, asthma and alveolitis. F-ENO conversions in the mixed adult population, in healthy adults and in children, showed the lowest deviation between estimated FENO from 100 ml s(-1) and measured F-ENO at 50 mL s(-1): -0 center dot 28 ppb, -0 center dot 44 ppb and 0 center dot 27 ppb, respectively. In patients with COPD, asthma and alveolitis, the deviation was -1 center dot 16 ppb, -1 center dot 68 ppb and 1 center dot 47 ppb, respectively. We proposed a valid model to convert F-ENO in healthy or mixed populations, as well as in subjects with obstructive pulmonary diseases and found it suitable for converting F-ENO measured with different expiratory flows to the standard flow in large epidemiological data, but not on individual level. In conclusion, a model to convert F-ENO from different flows to the standard flow was established and validated.Peer reviewe

Unique exercise lactate profile in muscle phosphofructokinase deficiency (Tarui disease); difference compared with McArdle disease

Introduction. Glycogen storage disease V (GSDV, McArdle disease) and GSDVII (Tarui disease) are the most common of the rare disorders of glycogen metabolism. Both are associated with low lactate levels on exercise. Our aim was to find out whether lactate response associated with exercise testing could distinguish between these disorders.Methods. Two siblings with Tarui disease, two patients with McArdle disease and eight healthy controls were tested on spiroergometric exercise tests with follow-up of venous lactate and ammonia. Results. A late increase of lactate about 3 times the basal level was seen 10-30 minutes after exercise in patients with Tarui disease being higher than in McArdle disease and lower than in the controls. Ammonia was increased in Tarui disease. Discussion. Our results suggest that follow up of lactate associated with exercise testing can be utilized in diagnostics to distinguish between different GSD diseases