A Case of Multiple Acyl Coenzyme: A Dehydrogenase Deficiency (MADD) in a Young Adult

Introduction : Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), also known as glutaric acidemia type II, is a rare, clinically heterogenous disorder often characterized by non-specific symptoms such as fatigue and muscle weakness but if undiagnosed may lead to severe metabolic derangements.

Case Description : MO is a 28 year old female with no pertinent past medical history who initially presented with fatigue and proximal muscle weakness (lower extremities > upper extremities) that developed a few months after she started a low carbohydrate diet. Her TSH was 5.45 uIU/mL (reference range: 0.550 – 4.780 uIU/mL) so she was started on Levothyroxine 25mcg daily. Her TSH improved but her symptoms continued to worsen.

Electromyography suggested an inflammatory, genetic, or metabolic myopathy of the lower extremities. Antibody panels for myositis, necrotizing myopathy, muscular dystrophy, and myasthenia gravis were normal. Muscle biopsy revealed vacuolated muscle fibers with lipid droplets suggestive of a lipid storage myopathy. Plasma acylcarnitine analysis revealed elevated medium-chain acyl carnitines. Genetic testing to determine the cause of lipid storage myopathy was sent.

Prior to her genetic testing results becoming available, her weakness progressed resulting in multiple falls. She was admitted to the hospital for falls and decreased oral intake due to bulbar weakness and dysphagia resulting in severe starvation ketoacidosis (pH 7.00, HCO3 < 10). She was treated with IV dextrose and sodium bicarbonate and her acidosis resolved. Her genetic testing results revealed a single heterozygous mutation in the electron transfer flavoprotein dehydrogenase (ETFDH) gene suggestive of MADD. She was started on a high carbohydrate–low fat diet and supplementation of riboflavin, carnitine, coenzyme Q10, and vitamin B12 with immediate improvement in her symptoms. Over several weeks her weakness resolved with treatment above and physical therapy.

Discussion : MADD is a rare disorder with its incidence at birth estimated to be 1 in 250,000. While it is possible adult-onset MADD is more rare since there are few reported cases, it is likely underdiagnosed given patients may present with non-specific symptoms such as fatigue and muscle weakness.

While easily treated once diagnosed, it may lead to severe metabolic derangements as in our patient if undiagnosed. Therefore, a higher index of suspicion should be considered to diagnose MADD especially when patients present with muscle weakness predominantly affecting the lower extremities, nausea and vomiting that develops after periods of fasting, intolerance of a low carbohydrate diet, or a metabolic acidosis of unclear etiology.