MADD-like pattern of acylcarnitines associated with sertraline use
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a primary mitochondrial dysfunction affecting mitochondrial fatty acid and protein metabolism, caused by biallelic pathogenic variants in ETFA, ETFB, or ETFDH genes. The heterogeneous phenotypes associated with MADD have been classified into three...
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Elsevier
2024-12-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426924000958 |
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| author | Filippo Ingoglia Mohsen Tanfous Benjamin Ellezam Katherine J. Anderson Marzia Pasquali Lorenzo D. Botto |
| author_facet | Filippo Ingoglia Mohsen Tanfous Benjamin Ellezam Katherine J. Anderson Marzia Pasquali Lorenzo D. Botto |
| author_sort | Filippo Ingoglia |
| collection | DOAJ |
| description | Multiple acyl-CoA dehydrogenase deficiency (MADD) is a primary mitochondrial dysfunction affecting mitochondrial fatty acid and protein metabolism, caused by biallelic pathogenic variants in ETFA, ETFB, or ETFDH genes. The heterogeneous phenotypes associated with MADD have been classified into three groups: neonatal onset with congenital anomalies (type 1), neonatal onset without congenital anomalies (type 2), and attenuated and/or later onset (type 3). Here, we present two cases with biochemical profiles mimicking late-onset MADD but negative genetic testing, associated with the use of sertraline, a commonly used antidepressant. Case 1 is a 22 yo woman diagnosed with depression and profound fatigue who was referred to the metabolic clinic because of carnitine deficiency and a plasma acylcarnitine profile with a MADD-like pattern. Case 2 is a 61 yo woman with a history of chronic fatigue who was admitted to the emergency department with difficulty swallowing, metabolic acidosis, and mild rhabdomyolysis. Plasma acylcarnitine profile showed a MADD-like pattern. The muscle biopsy revealed lipid droplet accumulation and proliferation of mitochondria with abnormal osmiophilic inclusions, and a biochemical assay of the respiratory chain showed a deficit in complex II activity. In both cases, urine organic acid profile was normal, and genetic tests did not detect variants in the genes involved in MADD. Sertraline was on their list of medications and considering its association with inhibition of mitochondrial function and rhabdomyolysis, the team recommended the discontinuation under medical supervision. In Case 1 after discontinuation, the plasma acylcarnitine test normalized, only to return abnormal when the patient resumed sertraline. In Case 2, after sertraline was discontinued rhabdomyolysis resolved, and the muscle biopsy and biochemical assay of the respiratory chain normalized. Although sertraline is considered a safe drug, these two cases suggest that the use of sertraline may be associated with a potentially reversible form of mitochondrial dysfunction mimicking MADD. Further studies are needed to confirm and estimate the risk of MADD-like presentations with the use of sertraline, as well as identifying additional contributing factors, including genetic factors. Metabolic physicians should consider sertraline use in the differential diagnosis of MADD, particularly when genetic testing is negative. |
| format | Article |
| id | doaj-art-13712aa79f9049628045d3f7e554c0c8 |
| institution | OA Journals |
| issn | 2214-4269 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj-art-13712aa79f9049628045d3f7e554c0c82025-08-20T02:36:42ZengElsevierMolecular Genetics and Metabolism Reports2214-42692024-12-014110114210.1016/j.ymgmr.2024.101142MADD-like pattern of acylcarnitines associated with sertraline useFilippo Ingoglia0Mohsen Tanfous1Benjamin Ellezam2Katherine J. Anderson3Marzia Pasquali4Lorenzo D. Botto5Department of Pathology, University of Utah, Salt Lake City, UT, USA; ARUP Laboratories, University of Utah, Salt Lake City, UT, USA; Corresponding author at: Department of Pathology, University of Utah, Salt Lake City, UT, USA.CHAUR CIUSSS-MCQ University Hospital, Trois-Rivieres, CanadaDepartment of Pathology, Sainte-Justine Hospital, Université de Montréal, Montréal, QC, CanadaDepartment of Pediatrics, Division of Clinical Genetics, University of Vermont, Burlington, VT, USADepartment of Pathology, University of Utah, Salt Lake City, UT, USA; CHAUR CIUSSS-MCQ University Hospital, Trois-Rivieres, Canada; Pediatrics, University of Utah, Salt Lake City, UT, USAPediatrics, University of Utah, Salt Lake City, UT, USAMultiple acyl-CoA dehydrogenase deficiency (MADD) is a primary mitochondrial dysfunction affecting mitochondrial fatty acid and protein metabolism, caused by biallelic pathogenic variants in ETFA, ETFB, or ETFDH genes. The heterogeneous phenotypes associated with MADD have been classified into three groups: neonatal onset with congenital anomalies (type 1), neonatal onset without congenital anomalies (type 2), and attenuated and/or later onset (type 3). Here, we present two cases with biochemical profiles mimicking late-onset MADD but negative genetic testing, associated with the use of sertraline, a commonly used antidepressant. Case 1 is a 22 yo woman diagnosed with depression and profound fatigue who was referred to the metabolic clinic because of carnitine deficiency and a plasma acylcarnitine profile with a MADD-like pattern. Case 2 is a 61 yo woman with a history of chronic fatigue who was admitted to the emergency department with difficulty swallowing, metabolic acidosis, and mild rhabdomyolysis. Plasma acylcarnitine profile showed a MADD-like pattern. The muscle biopsy revealed lipid droplet accumulation and proliferation of mitochondria with abnormal osmiophilic inclusions, and a biochemical assay of the respiratory chain showed a deficit in complex II activity. In both cases, urine organic acid profile was normal, and genetic tests did not detect variants in the genes involved in MADD. Sertraline was on their list of medications and considering its association with inhibition of mitochondrial function and rhabdomyolysis, the team recommended the discontinuation under medical supervision. In Case 1 after discontinuation, the plasma acylcarnitine test normalized, only to return abnormal when the patient resumed sertraline. In Case 2, after sertraline was discontinued rhabdomyolysis resolved, and the muscle biopsy and biochemical assay of the respiratory chain normalized. Although sertraline is considered a safe drug, these two cases suggest that the use of sertraline may be associated with a potentially reversible form of mitochondrial dysfunction mimicking MADD. Further studies are needed to confirm and estimate the risk of MADD-like presentations with the use of sertraline, as well as identifying additional contributing factors, including genetic factors. Metabolic physicians should consider sertraline use in the differential diagnosis of MADD, particularly when genetic testing is negative.http://www.sciencedirect.com/science/article/pii/S2214426924000958Multiple acyl-CoA dehydrogenase deficiency (MADD)SertralineMitochondrial dysfunctionAntidepressant medications |
| spellingShingle | Filippo Ingoglia Mohsen Tanfous Benjamin Ellezam Katherine J. Anderson Marzia Pasquali Lorenzo D. Botto MADD-like pattern of acylcarnitines associated with sertraline use Molecular Genetics and Metabolism Reports Multiple acyl-CoA dehydrogenase deficiency (MADD) Sertraline Mitochondrial dysfunction Antidepressant medications |
| title | MADD-like pattern of acylcarnitines associated with sertraline use |
| title_full | MADD-like pattern of acylcarnitines associated with sertraline use |
| title_fullStr | MADD-like pattern of acylcarnitines associated with sertraline use |
| title_full_unstemmed | MADD-like pattern of acylcarnitines associated with sertraline use |
| title_short | MADD-like pattern of acylcarnitines associated with sertraline use |
| title_sort | madd like pattern of acylcarnitines associated with sertraline use |
| topic | Multiple acyl-CoA dehydrogenase deficiency (MADD) Sertraline Mitochondrial dysfunction Antidepressant medications |
| url | http://www.sciencedirect.com/science/article/pii/S2214426924000958 |
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