Image_1_Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review.JPEG (77.96 kB)

Image_1_Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review.JPEG

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posted on 2021-05-10, 05:19 authored by Maria Anna Siano, Claudia Mandato, Lucia Nazzaro, Gennaro Iannicelli, Gian Paolo Ciccarelli, Ferdinando Barretta, Cristina Mazzaccara, Margherita Ruoppolo, Giulia Frisso, Carlo Baldi, Salvatore Tartaglione, Francesco Di Salle, Daniela Melis, Pietro Vajro

Diagnosis of pediatric steatohepatitis is a challenging issue due to a vast number of established and novel causes. Here, we report a child with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) presenting with an underrated muscle weakness, exercise intolerance and an atypically severe steatotic liver involvement. A systematic literature review of liver involvement in MADD was performed as well. Our patient is a 11-year-old otherwise healthy, non-obese, male child admitted for some weakness/asthenia, vomiting and recurrent severe hypertransaminasemia (aspartate and alanine aminotransferases up to ×20 times upper limit of normal). Hepatic ultrasound showed a bright liver. MRI detected mild lipid storage of thighs muscles. A liver biopsy showed a micro-macrovacuolar steatohepatitis with minimal fibrosis. Main causes of hypertransaminasemia were ruled out. Serum aminoacids (increased proline), acylcarnitines (increased C4-C18) and a large excretion of urinary glutaric acid, ethylmalonic, butyric, isobutyric, 2-methyl-butyric and isovaleric acids suggested a diagnosis of MADD. Serum acylcarnitines and urinary organic acids fluctuated overtime paralleling serum transaminases during periods of illness/catabolic stress, confirming their recurrent nature. Genetic testing confirmed the diagnosis [homozygous c.1658A > G (p.Tyr553Cys) in exon 12 of the ETFDH gene]. Lipid-restricted diet and riboflavin treatment rapidly ameliorated symptoms, hepatic ultrasonography/enzymes, and metabolic profiles. Literature review (37 retrieved eligible studies, 283 patients) showed that liver is an extramuscular organ rarely involved in late-onset MADD (70 patients), and that amongst 45 patients who had fatty liver only nine had severe presentation.

Conclusion: MADD is a disorder with a clinically heterogeneous phenotype. Our study suggests that MADD warrants consideration in the work-up of obesity-unrelated severe steatohepatitis.