Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature
Abstract Background Methylmalonic acidemia is a rare autosomal recessive disorder of propionate catabolism characterized by the accumulation of propionic acid and methylmalonic acid caused by methylmalonyl-CoA mutase deficiency. Clinical presentations range from acute deterioration in the neonatal p...
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2025-03-01
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| author | Fumiya Yamashita Satoshi Akamine Pin Fee Chong Kenichi Maeda Saori Kawakami Sooyoung Lee Masataka Ishimura Kei Murayama Yasunari Sakai Ryutaro Kira |
| author_facet | Fumiya Yamashita Satoshi Akamine Pin Fee Chong Kenichi Maeda Saori Kawakami Sooyoung Lee Masataka Ishimura Kei Murayama Yasunari Sakai Ryutaro Kira |
| author_sort | Fumiya Yamashita |
| collection | DOAJ |
| description | Abstract Background Methylmalonic acidemia is a rare autosomal recessive disorder of propionate catabolism characterized by the accumulation of propionic acid and methylmalonic acid caused by methylmalonyl-CoA mutase deficiency. Clinical presentations range from acute deterioration in the neonatal period to later onset with a heterogeneous clinical course. Metabolite accumulation results in systemic involvement, affecting the nervous, gastrointestinal, and renal system functions and causing cardiomyopathy. Bone marrow dysfunction manifesting as neutropenia and anemia is a common hematological finding. Although rare, three cases of secondary hemophagocytosis were documented. Case presentation An 18-year-old male patient diagnosed with methylmalonic acidemia presented with vomiting and altered mental status. He had a medical history of presumably hemophagocytic lymphohistiocytosis (HLH) at the age of 17 months. Physical examination, laboratory tests, and bone marrow aspiration results met the HLH-2004 diagnostic criteria, confirming a recurrent HLH. Although he recovered after intensive treatment, his cognitive function declined. Retrospective analysis revealed higher serum levels of ferritin during acute decompensations compared with nonattack periods. Correlation analysis revealed a strong relationship between serum ferritin and propionylcarnitine, one of the major propionyl-CoA-derived metabolites. Conclusions HLH is a rare and underrecognized hematologic emergency in methylmalonic acidemia, and its early diagnosis and treatment are critical. Serum ferritin may be a useful clinical biomarker in the diagnosis of HLH-associated attacks in methylmalonic acidemia. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-03-01 |
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| series | BMC Pediatrics |
| spelling | doaj-art-ac9fb7deac764489876dcf06c25cf6a22025-08-20T03:07:41ZengBMCBMC Pediatrics1471-24312025-03-012511710.1186/s12887-025-05613-9Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literatureFumiya Yamashita0Satoshi Akamine1Pin Fee Chong2Kenichi Maeda3Saori Kawakami4Sooyoung Lee5Masataka Ishimura6Kei Murayama7Yasunari Sakai8Ryutaro Kira9Department of Pediatric Neurology, Fukuoka Children’s HospitalDepartment of Pediatric Neurology, Fukuoka Children’s HospitalDepartment of Pediatric Neurology, Fukuoka Children’s HospitalDepartment of Pediatric Neurology, Fukuoka Children’s HospitalDepartment of Pediatric Neurology, Fukuoka Children’s HospitalDepartment of Intensive Care, Fukuoka Children’s HospitalDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu UniversityCenter for Medical Genetics, Department of Metabolism, Chiba Children’s HospitalDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Pediatric Neurology, Fukuoka Children’s HospitalAbstract Background Methylmalonic acidemia is a rare autosomal recessive disorder of propionate catabolism characterized by the accumulation of propionic acid and methylmalonic acid caused by methylmalonyl-CoA mutase deficiency. Clinical presentations range from acute deterioration in the neonatal period to later onset with a heterogeneous clinical course. Metabolite accumulation results in systemic involvement, affecting the nervous, gastrointestinal, and renal system functions and causing cardiomyopathy. Bone marrow dysfunction manifesting as neutropenia and anemia is a common hematological finding. Although rare, three cases of secondary hemophagocytosis were documented. Case presentation An 18-year-old male patient diagnosed with methylmalonic acidemia presented with vomiting and altered mental status. He had a medical history of presumably hemophagocytic lymphohistiocytosis (HLH) at the age of 17 months. Physical examination, laboratory tests, and bone marrow aspiration results met the HLH-2004 diagnostic criteria, confirming a recurrent HLH. Although he recovered after intensive treatment, his cognitive function declined. Retrospective analysis revealed higher serum levels of ferritin during acute decompensations compared with nonattack periods. Correlation analysis revealed a strong relationship between serum ferritin and propionylcarnitine, one of the major propionyl-CoA-derived metabolites. Conclusions HLH is a rare and underrecognized hematologic emergency in methylmalonic acidemia, and its early diagnosis and treatment are critical. Serum ferritin may be a useful clinical biomarker in the diagnosis of HLH-associated attacks in methylmalonic acidemia.https://doi.org/10.1186/s12887-025-05613-9Methylmalonic acidemiaSecondary hemophagocytic lymphohistiocytosisMetabolic attackFerritin |
| spellingShingle | Fumiya Yamashita Satoshi Akamine Pin Fee Chong Kenichi Maeda Saori Kawakami Sooyoung Lee Masataka Ishimura Kei Murayama Yasunari Sakai Ryutaro Kira Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature BMC Pediatrics Methylmalonic acidemia Secondary hemophagocytic lymphohistiocytosis Metabolic attack Ferritin |
| title | Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature |
| title_full | Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature |
| title_fullStr | Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature |
| title_full_unstemmed | Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature |
| title_short | Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature |
| title_sort | methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis a case report and review of the literature |
| topic | Methylmalonic acidemia Secondary hemophagocytic lymphohistiocytosis Metabolic attack Ferritin |
| url | https://doi.org/10.1186/s12887-025-05613-9 |
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