Clinical study Phenotype of carnitine palmitoyltransferase II (CPT II) deficiency: A questionnaire-based survey Pushpa Raj Joshi a,⇑ , Marcus Deschauer b , Stephan Zierz a a Department of Neurology, Martin-Luther-University Halle-Wittenberg, Germany b Department of Neurology, Technical University Munich, Munich, Germany article info Article history: Received 13 July 2018 Accepted 5 November 2018 Keywords: CPT II Exercise Myalgia Rhabdomyolysis Questionnaire abstract Wide spectrums of symptoms besides muscle weakness, different triggering factors and varied muscles involvement are associated with CPT II deficiency. However, systematic clinical characterization of CPT II deficiency is not known. A Questionnaire-based retrospective study on 13 biochemically and genetically confirmed CPT II deficient patients was performed to analyze these aspects. Attacks of myalgia (13/13 patients), weakness (13/13) and rhabdomyolysis (10/13 patients) were most frequently reported. The number of attacks ranged from 1 to 85/year. Common triggers were exercise (13/13), fasting (13/13), cold (12/13) and infections (12/13). Exercise lasting from 15 to 60 min was sufficient for attacks in 9/13 patients, 1–4 h in 3/13 patients and more than 4 h in 1/13 patient. 2/13 patients required dialysis. Limb muscles were affected slightly more often than other muscles. Mean intensity of pain in visual ana- logue scale (VAS) during regular attack was 4.77 (±1.36). Frequency and severity of attacks did not increase during the course of disease in 10/13 patients. 7/13 patients quit sports after the symptoms emerged. 3/13 patients changed their profession permanently. Increased number of attacks were posi- tively correlated with higher BMI (P = 0.05). Body rest, carbohydrate-rich nutrients and fluid- supplement mitigated the pain. After the first attack [Mean: 9.7 (±4.46) years], diagnosis took an average of 26.7 (± 13.06) years. In myopathic CPT II deficiency, frequencies of attacks are highly variable. Generally, the myopathic form is a mild form. However, severe patients requiring dialysis due to kidney failure could be present. Individuals with higher BMI are at risk of developing more frequent attacks. Ó 2018 Elsevier Ltd. All rights reserved. 1. Introduction Muscle carnitine palmitoyltransferase II (CPT II) deficiency is the most common inherited disorder of long-chain fatty acid oxi- dation [1–3]. In skeletal muscles, energy demand is increased dur- ing strenuous activities such as prolonged exercise, fasting and exposure to cold. The extra energy required during these condi- tions is met by utilization of long chain fatty acids within the mito- chondria. Transport of long chain fatty acids inside the mitochondria is facilitated by CPT II at the inner mitochondrial membrane [4]. CPT II deficiency presents with three phenotypes: lethal neona- tal form, severe infantile hepatocardiomuscular form [5], and the most frequent classical myopathic form with mild phenotype. The myopathic form is clinically characterized by recurrent epi- sodes of myalgia, muscle weakness and rhabdomyolysis triggered by prolonged exercise, fasting, exposure to cold, fever and emo- tional stress. Persistent muscle weakness is rarely seen in CPT II deficiency [3,6,7]. Between the attacks, neurological examination and muscle biopsy are usually normal. The myopathic form can manifest from infancy to adulthood [3]. A common p.Ser113Leu mutation in the CPT 2 gene is identified in about 90% of patients [3,8]. Although there are few studies on symptoms and triggers in CPT II deficient patients [3,6–8], there is no detailed information on their characteristics, affected muscles, mitigating methods, disease course and diagnosis timeline. In the present study, we analyzed the phenotype of biochemically and genetically confirmed CPT II deficient patients based on a questionnaire survey. 2. Patients and methods 2.1. Patients Out of 14 CPT II deficient patients undergoing regular follow-up in our department, 13 patients participated in the study. A written https://doi.org/10.1016/j.jocn.2018.11.023 0967-5868/Ó 2018 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany. E-mail address: pushpa.joshi@medizin.uni-halle.de (P.R. Joshi). Journal of Clinical Neuroscience 59 (2019) 32–36 Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn