Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review
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 li...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-05-01
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Series: | Frontiers in Pediatrics |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2021.672004/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Anna Siano Claudia Mandato Lucia Nazzaro Gennaro Iannicelli Gian Paolo Ciccarelli Ferdinando Barretta Ferdinando Barretta Cristina Mazzaccara Cristina Mazzaccara Margherita Ruoppolo Margherita Ruoppolo Giulia Frisso Giulia Frisso Carlo Baldi Salvatore Tartaglione Francesco Di Salle Daniela Melis Daniela Melis Pietro Vajro Pietro Vajro Pietro Vajro |
spellingShingle |
Maria Anna Siano Claudia Mandato Lucia Nazzaro Gennaro Iannicelli Gian Paolo Ciccarelli Ferdinando Barretta Ferdinando Barretta Cristina Mazzaccara Cristina Mazzaccara Margherita Ruoppolo Margherita Ruoppolo Giulia Frisso Giulia Frisso Carlo Baldi Salvatore Tartaglione Francesco Di Salle Daniela Melis Daniela Melis Pietro Vajro Pietro Vajro Pietro Vajro Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review Frontiers in Pediatrics steatohepatitis hypertransaminasemia fatty liver MADD case report |
author_facet |
Maria Anna Siano Claudia Mandato Lucia Nazzaro Gennaro Iannicelli Gian Paolo Ciccarelli Ferdinando Barretta Ferdinando Barretta Cristina Mazzaccara Cristina Mazzaccara Margherita Ruoppolo Margherita Ruoppolo Giulia Frisso Giulia Frisso Carlo Baldi Salvatore Tartaglione Francesco Di Salle Daniela Melis Daniela Melis Pietro Vajro Pietro Vajro Pietro Vajro |
author_sort |
Maria Anna Siano |
title |
Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review |
title_short |
Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review |
title_full |
Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review |
title_fullStr |
Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review |
title_full_unstemmed |
Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic Review |
title_sort |
hepatic presentation of late-onset multiple acyl-coa dehydrogenase deficiency (madd): case report and systematic review |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pediatrics |
issn |
2296-2360 |
publishDate |
2021-05-01 |
description |
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. |
topic |
steatohepatitis hypertransaminasemia fatty liver MADD case report |
url |
https://www.frontiersin.org/articles/10.3389/fped.2021.672004/full |
work_keys_str_mv |
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doaj-323ee345e50949f294ff867be83089632021-05-10T07:52:05ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-05-01910.3389/fped.2021.672004672004Hepatic Presentation of Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency (MADD): Case Report and Systematic ReviewMaria Anna Siano0Claudia Mandato1Lucia Nazzaro2Gennaro Iannicelli3Gian Paolo Ciccarelli4Ferdinando Barretta5Ferdinando Barretta6Cristina Mazzaccara7Cristina Mazzaccara8Margherita Ruoppolo9Margherita Ruoppolo10Giulia Frisso11Giulia Frisso12Carlo Baldi13Salvatore Tartaglione14Francesco Di Salle15Daniela Melis16Daniela Melis17Pietro Vajro18Pietro Vajro19Pietro Vajro20Postgraduate School of Pediatrics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, ItalyUnit of Pediatrics 1, AORN Santobono-Pausilipon, Naples, ItalyPediatric Clinic, AOU “S. Giovanni di Dio and Ruggi d'Aragona”, Salerno, ItalyPediatric Clinic, AOU “S. Giovanni di Dio and Ruggi d'Aragona”, Salerno, ItalyPostgraduate School of Pediatrics, Faculty of Medicine University of Naples Federico II, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, Faculty of Medicine University of Naples Federico II, Naples, ItalyCEINGE-Biotecnologie Avanzate s.c.a r.l., Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, Faculty of Medicine University of Naples Federico II, Naples, ItalyCEINGE-Biotecnologie Avanzate s.c.a r.l., Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, Faculty of Medicine University of Naples Federico II, Naples, ItalyCEINGE-Biotecnologie Avanzate s.c.a r.l., Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, Faculty of Medicine University of Naples Federico II, Naples, ItalyCEINGE-Biotecnologie Avanzate s.c.a r.l., Naples, ItalyPathology Unit, AOU “S. Giovanni di Dio and Ruggi d'Aragona”, Salerno, ItalyRadiology Unit, AOU “S. Giovanni di Dio and Ruggi d'Aragona”, Salerno, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, ItalyPostgraduate School of Pediatrics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, ItalyPediatric Clinic, AOU “S. Giovanni di Dio and Ruggi d'Aragona”, Salerno, ItalyPostgraduate School of Pediatrics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, ItalyPediatric Clinic, AOU “S. Giovanni di Dio and Ruggi d'Aragona”, Salerno, ItalyPostgraduate School of Pediatrics, Faculty of Medicine University of Naples Federico II, Naples, ItalyDiagnosis 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.https://www.frontiersin.org/articles/10.3389/fped.2021.672004/fullsteatohepatitishypertransaminasemiafatty liverMADDcase report |