39 Pilot study: Modiﬁed Atkins diet trial for adult-onset mitochondrial myopathy Presenter: Anu Suomalainen Soﬁa Ahola-Erkkiläa, Mari Auranena, Pirjo Isohannia, Nina Lundbomc, Päivi Piiriläd, Kirsi Pietiläinenb, Anu Suomalainena a Biomedicum-Helsinki, Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland b Diabetes and Obesity, University of Helsinki, Helsinki, Finland c Helsinki University Central Hospital, Department of Radiology, Helsinki, Finland d Helsinki University Central Hospital, Department of Physiology, Helsinki, Finland Body of abstract: Evidence from mouse models of mitochondrial disorders suggests that nutrient type, nutrient signaling and nutritional supplements contribute to manifestations of mitochondrial disorders. In a late-onset myopathy mouse, we showed previously that a high-fat diet improved mitochondrial function and prevented development of abnormal mitochondrial ultrastructure. Here we report the ﬁrst pilot intervention study with a modiﬁed Atkins diet for adult patients with mitochondrial disorders and their matched controls, to assess potential to use this dietary intervention as a treatment for these disorders. The patient group included two patients with single mtDNA deletion, and three patients with autosomal dominant mitochondrial myopathy with multiple mtDNA deletions, caused by a mutation in Twinkle gene— homologous to the mouse model studied before, and 10 healthy controls. The study subjects underwent a structured diet protocol designed by a nutritionist, isocaloric, as we did not aim for weight loss. The patients kept a pre-diet food diary, followed a standardized “normal” diet for two weeks, and then progressed to a lowcarbohydrate Atkins diet with 10 g of carbohydrates per day. The clinical status of the patients was examined before and after the diet by a neurologist, a physiotherapist (muscle strength), and a physiatrist (spiroergometry, lactate dynamics), and their liver fat contents were followed by MRI. A muscle biopsy was taken before and after the study, as well as a multitude of serum tests in several time points. The wellbeing and quality of life was followed by questionnaires, and the clinical status of the study subjects was closely followed up during the diet. All patients reached ketosis, similar to controls. We report a major effect of this diet after 1.5 weeks of the Atkins diet, similar in all the mitochondrial patients. The preliminary results show that nutrition can affect in a crucial way progression of adult mitochondrial myopathies and that all patients should meet a nutritionist as part of their care.
Chronically progressive myopathy and neuropathy are frequently seen in mitochondrial disease. Acute onset mitochondrial myopathy with polyneuropathy is rare. Here we report a patient presenting acute lactic acidosis and muscle weakness, with muscle biopsy showing impressive ragged red ﬁbers and mitochondrial number and morphologic abnormalities on electron microscopy. We also found heterozygous A3243G mutations in his blood. Case report: A 30 year old male patient complained of muscle pain at the calf and inner thigh for 1 month. This spread to his arms for one week. 4 days before he felt palpitation and ECG showed tachycardia. Urine acid was elevated at 655umol/L. Creatine kinase(CK) was elevated at 1359 IU/L. He was hospitalized with the diagnosis of “viral myocarditis”. Echocardiography was normal. Blood gas analysis showed pH 7.317 and LAC 10.20 mmol/L. CK was 1289 U/L at admission. On the 3rd day of admission, the patient complained of lumbar pain and abdominal pain and was partially relieved by morphine injection. Physical examination showed that the abdomen was soft, muscle strength was normal, and anal exhaust was normal. Blood gas analysis showed pH 6.708 and LAC 15.00 mmol/L. CK increased to 1344U/L. Tracheal intubation was used and pH was corrected with sodium bicarbonate. However LAC and CK continued to increase up to 17 mmol/L and 2021 IU/L 20 h later. At the 5th day, blood gas analysis showed PH 7.38, LAC 8.2 mmol/L, they found out muscle weakness with the muscle strength at grade 3/5 on the arm and grade 2/5 on the leg, and also deep tendon reﬂex disappeared. Lumbar puncture at the 7th day and 13th day showed normal white blood cells and normal protein. He has exercise intolerance from childhood but family history was unremarkable. EMG was done at the 11th day and muscle biopsy was done at the 16th day. mtDNA point mutations were also detected. The patient was treated with coenzyme Q10, l-carnitine, IVIG, methylprednisolone and active rehabilitation. At the 44th day of admission, his muscle strength recovered to grade 4/5 on the arm and grade 3+/5 on the leg. His LAC ﬂuctuated at 5.60 mmol/L. Results: EMG showed a dramatic decrease of motor amplitude with median nerve at 0.624 mV and peroneal nerve at 0.143 mV, nerve conduct was at 50.4 m/s and 43.1 m/s respectively. Sensory nerve amplitude was also moderately reduced. Muscle biopsy showed impressive ragged red ﬁbers and normal lipid and glycogen. EM showed a dramatic increase in mitochondrion and morphologic abnormality. No paracrystal line was seen. Heterozygous A3243G mutation was found in his blood. SOLID mtDNA sequencing is in progress. Mitochondrial myopathies with chronic muscle weakness and ptosis are common. This patient came with acute lactic acidosis and acute axonal polyneuropathy. Mitochondrial disease was proven with RRF, dramatic abnormality on EM and mtDNA mutation. He may have other mtDNA mutations or nDNA mutations which need to be revealed further. doi:10.1016/j.mito.2013.07.037
Mitochondrial myopathy presenting as acute lactic acidosis with motor and sensory axonal polyneuropathy Presenter: Ailian Du Ailian Dua,⁎, Ying Zhoub, Yuquan Shaoc, Zhiying Wud a Department of Neurology, Second Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China b Department of Cardiology, Second Afﬁliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China c Department of Neurology, Sir Run Run Shao Hospital, School of Medicine, Zhejiang University, Hangzhou, China d Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China ⁎Corresponding author. E-mail: [email protected]
41 Clinical re-sequencing for the diagnosis of mitochondrial disorders reveals high genetic heterogeneity Presenter: Jeana T. DaRe Jeana T. DaRea, Valeria Vastab, John Penna, Justin Leightona, Si Houn Hahnb,c a Transgenomic, Inc., 5Science Park, New Haven, CT 06511, USA b Seattle Children's Hospital Research Institute, 1900 9th Ave., Seattle, WA 98101, USA c Department of Pediatrics, Division of Genetic Medicine, University of Washington, School of Medicine/Seattle Children's Hospital, 4800 Sand Point Way, Seattle, WA 98105, USA