{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:54:09Z","timestamp":1790679249847,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malonic aciduria is an extremely rare inborn error of metabolism due to malonyl-CoA decarboxylase deficiency. This enzyme is encoded by the MLYCD (Malonyl-CoA Decarboxylase) gene, and the disease has an autosomal recessive inheritance. Malonic aciduria is characterized by systemic clinical involvement, including neurologic and digestive symptoms, metabolic acidosis, hypoglycemia, failure to thrive, seizures, developmental delay, and cardiomyopathy. We describe here two index cases belonging to the same family that, despite an identical genotype, present very different clinical pictures. The first case is a boy with neonatal metabolic symptoms, abnormal brain MRI, and dilated cardiomyopathy. The second case, the cousin of the first patient in a consanguineous family, showed later symptoms, mainly with developmental delay. Both patients showed high levels of malonylcarnitine on acylcarnitine profiles and malonic acid on urinary organic acid chromatographies. The same homozygous pathogenic variant was identified, c.346C &gt; T; p. (Gln116*). We also provide a comprehensive literature review of reported cases. A review of the literature yielded 52 cases described since 1984. The most common signs were developmental delay and cardiomyopathy. Increased levels of malonic acid and malonylcarnitine were constant. Presentations ranged from neonatal death to patients surviving past adolescence. These two cases and reported patients in the literature highlight the inter- and intrafamilial variability of malonic aciduria.<\/jats:p>","DOI":"10.3390\/ijms222312633","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"12633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Heterogenous Clinical Landscape in a Consanguineous Malonic Aciduria Family"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8382-056X","authenticated-orcid":false,"given":"Sarah","family":"Snanoudj","sequence":"first","affiliation":[{"name":"Department of Metabolic Biochemistry, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Torre","sequence":"additional","affiliation":[{"name":"Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Sudri\u00e9-Arnaud","sequence":"additional","affiliation":[{"name":"Department of Metabolic Biochemistry, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenaig","family":"Abily-Donval","sequence":"additional","affiliation":[{"name":"Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Goldenberg","sequence":"additional","affiliation":[{"name":"Department of Genetics and Reference Center for Developmental Disorders, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajja S.","family":"Salomons","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Department of Paediatric Metabolic Diseases, Emma Children\u2019s Hospital, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, Vrije Universiteit Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-148X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Marret","sequence":"additional","affiliation":[{"name":"Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-7270","authenticated-orcid":false,"given":"Soumeya","family":"Bekri","sequence":"additional","affiliation":[{"name":"Department of Metabolic Biochemistry, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-2678","authenticated-orcid":false,"given":"Abdellah","family":"Tebani","sequence":"additional","affiliation":[{"name":"Department of Metabolic Biochemistry, UNIROUEN, INSERM U1245, CHU Rouen, Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1086\/302492","article-title":"The molecular basis of malonyl-CoA decarboxylase deficiency","volume":"65","author":"FitzPatrick","year":"1999","journal-title":"Am. 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