MADD is a treatable disorder of fatty acid oxidation.In the last eight years we have diagnosed 10 patients with adult-onset MADD in our part of Sweden, Sydöstra sjukvårdsregionen, with a population of just over one million people.This makes MADD the most common fatty oxidation diagnosis in adults in the area.The age of onset ranges from 22 to 74 years of age (mean 45) and 70% are female.Eight patients presented with proximal muscular weakness, often more pronounced in the legs than arms.Four patients also had weakness of the neck.Six patients had breathing problems, five had impaired sensory function whereas muscular fatigue or myalgia was experienced by four patients, respectively.Noted comorbidities were anxiety/depression (70%), chronic pain (40%), hypertension (30%) and hypothyroidism (20%).Seven patients were on medication with sertraline, four on cobalamin and folic acid and two on levothyroxine.All patients had slightly elevated creatine kinase (CK).Muscle biopsy showed increased amount of neutral lipids within muscle fibers in all patients.Acylcarnitine profiles in plasma showed a typical pattern for MADD in all patients.Neurophysiology showed myopathy in six patients and a sensory axonal neuropathy in three.A thorough genetic investigation was performed in 7 patients, but a genetic cause was only found in one of the patients, suggesting a non-genetic aetiology.All patients were treated with riboflavin, 150-400 mg/day (mean 255 mg/d).Two patients received carnitine 2g/day, and one patient Q10, in addition.Treatment resulted in full recovery of three and improvement in six patients.Sensory symptoms did not ameliorate.The CK was normalised in all patients and acylcarnitines were improved.Results from individual patients will be presented.

Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inherited metabolic disorders causing a deficiency in the catabolism of branched-chain amino acids, cholesterol, and odd-chain fatty acids. Both patient groups report exercise intolerance and fatigue. A previous case study found impaired lipolysis and blunted fat oxidation during exercise in a patient with PA, suggesting PA being a metabolic myopathy. This may partly explain the exercise intolerance and fatigue reported in the patient group. This study aimed to investigate fat and glucose metabolism during exercise in patients with PA and MMA. We included four patients, two patients with MMA and two with PA. The patients performed a submaximal exercise test on a cycle ergometer, working at a workload corresponding to 50% of their maximal oxygen capacity. Fat and glucose metabolism were quantified during exercise via continuous infusion of stable isotope-labeled glucose and palmitate (long-chain fatty acid) and indirect calorimetry. The results were compared to matched healthy controls. We found that all patients presented with impaired lipolysis, reflected by low lipolytic rate compared to healthy controls (1.5±0.3 vs. 4.0±0.4, p=0.005). The patients had low work capacity as illustrated by significantly higher perceived exhaustion (Borg scale) and heart rate than healthy controls (Borg: 13.8±0.3 vs. 8.0±0.4, p<0.001. Heart rate: 115.6±5.9 vs. 84.6±2.1, p=0.0004). Lastly, the patients could not increase their fat oxidation to the same extent as the healthy controls during exercise, reflected by the low mean rate of palmitate oxidation (0.8±0.3 vs 2.1±0.3, p=0.02). Our findings indicate that both PA and MMA should be considered metabolic myopathies, which may explain the reported exercise intolerance and fatigue. Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inherited metabolic disorders causing a deficiency in the catabolism of branched-chain amino acids, cholesterol, and odd-chain fatty acids. Both patient groups report exercise intolerance and fatigue. A previous case study found impaired lipolysis and blunted fat oxidation during exercise in a patient with PA, suggesting PA being a metabolic myopathy. This may partly explain the exercise intolerance and fatigue reported in the patient group. This study aimed to investigate fat and glucose metabolism during exercise in patients with PA and MMA. We included four patients, two patients with MMA and two with PA. The patients performed a submaximal exercise test on a cycle ergometer, working at a workload corresponding to 50% of their maximal oxygen capacity. Fat and glucose metabolism were quantified during exercise via continuous infusion of stable isotope-labeled glucose and palmitate (long-chain fatty acid) and indirect calorimetry. The results were compared to matched healthy controls. We found that all patients presented with impaired lipolysis, reflected by low lipolytic rate compared to healthy controls (1.5±0.3 vs. 4.0±0.4, p=0.005). The patients had low work capacity as illustrated by significantly higher perceived exhaustion (Borg scale) and heart rate than healthy controls (Borg: 13.8±0.3 vs. 8.0±0.4, p<0.001. Heart rate: 115.6±5.9 vs. 84.6±2.1, p=0.0004). Lastly, the patients could not increase their fat oxidation to the same extent as the healthy controls during exercise, reflected by the low mean rate of palmitate oxidation (0.8±0.3 vs 2.1±0.3, p=0.02). Our findings indicate that both PA and MMA should be considered metabolic myopathies, which may explain the reported exercise intolerance and fatigue.