Abstract Details

Title Late-onset multiple acyl-CoA dehydrogenase deficiency with a complex genetic finding

Topic Child Neurology and Developmental Neurology

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-066

Objective To describe a rare case of late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) with complex interpretation of the genetic study.

Background MADD is a rare autosomic recessive inborn error of metabolism, caused by mutations in the ETFA, ETFB or ETFDH genes and affecting fatty acid and amino acid oxidation, with significant clinical and genetic heterogeneity. Clinical presentation can range from severe neonatal forms to mild late-onset (childhood/adult) disease with episodic metabolic decompensation, myopathy and respiratory failure.

Design/Methods Clinical history, neurological examination and diagnostic workup were retrospectively reviewed.

Results A 36-year-old man had a history of generalized muscle weakness and pain, exacerbated after exercise, since he was 6 years old. There was an insidious progression of symptoms with subsequent functional impairment. Diagnostic workup in adulthood revealed maintained increased serum values of creatine kinase (3-5 times the upper reference limit), frequent ventricular extrasystoles in electrocardiography, diminished functional capacity in cardiac stress test and normal echocardiogram. Acylcarnitine profile analysis revealed low C2 and free carnitine and increased C5-C14 carnitine, providing a biochemical diagnosis for MADD. Genetic study identified a previously described heterozygous pathogenic mutation in the ETFDH gene (p.P534L/c.1115A>G) and previously not described probably pathogenic heterozygous mutations in the ETFA (p.T171I/c.512C>T) and ETFB (p.T245M/c.733C>T) genes. Genetic study of the parents was impossible for the father but the asymptomatic mother had the same mutations in the ETFDH and ETFA genes. Currently, the patient is clinically stabilized with specific diet and a therapeutic regimen including levocarnitine and riboflavin.

Conclusions

We report a MADD patient with genetic findings of complex interpretation. With the first description of combined polygenic heterozygosity in MADD, knowledge of the interaction between different flavoproteins is essential to understand genotype-phenotype correlation. While clinical findings in MADD are non-specific, exercise-related muscle pain and weakness in young patients should raise its suspicion and biochemical findings can often support the diagnosis.

Authors/Disclosures
Joao L. Durães, MD (Hospitais Da Universidade De Coimbra) PRESENTER	No disclosure on file
	No disclosure on file

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