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Case Reports
. 2022 Nov 17;9(1):13-16.
doi: 10.1016/j.aace.2022.11.004. eCollection 2023 Jan-Feb.

Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Leading to Severe Metabolic Acidosis in a Young Adult

Karthik Subbu  1 , Clara Hildebrandt  2 , Donald Caraccio  1
Affiliations
Case Reports

Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Leading to Severe Metabolic Acidosis in a Young Adult

Karthik Subbu et al. AACE Clin Case Rep. .

Abstract

Background: Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder affecting fatty acid oxidation. Incidence at birth is estimated at 1:250 000, but type III presents in adults. It is characterized by nonspecific symptoms but if undiagnosed may cause ketoacidosis and rhabdomyolysis. A review of 350 patients found less than one third presented with metabolic crises. Our objective is to describe an adult with weakness after carbohydrate restriction that developed a pulmonary embolism and ketoacidosis, and was diagnosed with MADD type III.

Case report: A 27-year-old woman with obesity presented to the hospital with fatigue and weakness worsening over months causing falls and decreased intake. She presented earlier to clinic with milder symptoms starting months after initiating a low carbohydrate diet. Testing revealed mild hypothyroidism and she started Levothyroxine for presumed hypothyroid myopathy but progressed. Muscle biopsy suggested a lipid storage myopathy. Genetic testing revealed a mutation in the ETFDH (electron transfer flavoprotein dehydrogenase) gene likely pathogenic for MADD; however, before this was available she developed severe ketoacidosis and rhabdomyolysis. She empirically started a low-fat diet, carnitine, cyanocobalamin, and coenzyme Q10 supplementation with improvement. Over months her energy and strength normalized.

Discussion: MADD may cause ketoacidosis and rhabdomyolysis but this is rare in adults. Diagnosis requires clinical suspicion followed by biochemical and genetic testing. It should be considered when patients present with weakness or fasting intolerance. Treatment includes high carbohydrate, low-fat diets, supplementation, and avoiding fasting.

Conclusion: There should be greater awareness to consider MADD in adults presenting with neuromuscular symptoms, if untreated it may cause severe metabolic derangements.

Keywords: CK, creatine kinase; ETFA, electron transfer flavoprotein A; ETFB, electron transfer flavoprotein B; ETFDH, electron transfer flavoprotein dehydrogenase; MADD, multiple acyl-coenzyme A dehydrogenase deficiency; TSH, thyroid stimulating hormone; electron transfer flavoprotein dehydrogenase; glutaric aciduria type II; inborn errors of metabolism; lipid storage myopathy; multiple acyl-coenzyme A dehydrogenase deficiency; muscle weakness.

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Conflict of interest statement

We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Creatine kinase levels over the course of disease. Levels rose precipitously during hospital admission and normalized by discharge. (Gray shaded area corresponds to reference range: 34.0-145.0 units/L). EMG = electromyography; ER = extended release; ICU = intensive care unit.
Fig. 2
Fig. 2
Acetylcarnitine levels before and after treatment. Profile prior to treatment showed a trend toward elevation of long chain acylcarnitine levels that resolved after treatment (Flow Injection Analysis, Tandem Mass Spectrometry, Mayo Clinic Laboratories).
See this image and copyright information in PMC

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