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

Abstract

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 modifiedAtkins 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.

Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms

“…Finally, there is a recent case study of a patient with phosphofructokinase deficiency (GSD VII, Tarui disease) who was treated with an MAD (ratio of ~1:1 fat/protein and carbohydrates restricted to 10 g/day) for 5 years. This therapy greatly alleviated muscle symptoms and improved exercise performance 125 . Taken together, these preliminary clinical observations suggest that KDs in one form or another have potential in ameliorating clinical symptoms in patients with GSD, and that such dietary interventions are not solely beneficial for blocking seizure activity.…”

“…This therapy greatly alleviated muscle symptoms and improved exercise performance. 125 Taken together, these preliminary clinical observations suggest that KDs in one form or another have potential in ameliorating clinical symptoms in patients with GSD, and that such dietary interventions are not solely beneficial for blocking seizure activity.…”

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

“…Also, favourable effects of high-fat diet in other types of GSDs with muscle involvement have been reported. Similä et al [20] observed that the muscle symptoms and exercise tolerance of the patient with GSD type VII improved during 5 years of KD. In contrast to these findings, Valayannopoulos et al [17] have emphasized that when exogenous D, L-3-hydroxybutyrate was received as a source of KBs, CK levels remained elevated in patients.…”

Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence

“…Indeed, phosphofructokinase deficiency (Tarui’s disease), a hereditary disorder that alters the ability of muscles to utilize carbohydrates (such as glucose) for energy production, was reported in patients suffering from muscle cramps, exercise intolerance and recurrent episodes of rhabdomyolysis during statin therapy [ 110 ]. Similar considerations have to be extended to other metabolic myopathies as muscle β-enolase deficiency, an ultrarare metabolic myopathy due to impairment of terminal glycolysis described in few adult patients with muscle fatigability, myalgia and increased CK values after intense physical exercise [ 111 , 112 , 113 ].…”