Yamashita Fumiya, Akamine Satoshi, Chong Pin Fee, Maeda Kenichi, Kawakami Saori, Lee Sooyoung, Ishimura Masataka, Murayama Kei, Sakai Yasunari, Kira Ryutaro
Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
BMC Pediatr. 2025 Mar 31;25(1):259. doi: 10.1186/s12887-025-05613-9.
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.
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.
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.
甲基丙二酸血症是一种罕见的常染色体隐性丙酸分解代谢障碍疾病，其特征是由于甲基丙二酰辅酶A变位酶缺乏导致丙酸和甲基丙二酸蓄积。临床表现从新生儿期的急性恶化到较晚发病且临床病程各异。代谢物蓄积导致全身受累，影响神经、胃肠和肾脏系统功能，并引起心肌病。表现为中性粒细胞减少和贫血的骨髓功能障碍是常见的血液学表现。虽然罕见，但有3例继发性噬血细胞增多症的记录。
一名18岁男性患者被诊断为甲基丙二酸血症，出现呕吐和精神状态改变。他在17个月大时曾有疑似噬血细胞性淋巴组织细胞增生症（HLH）的病史。体格检查、实验室检查和骨髓穿刺结果符合HLH-2004诊断标准，确诊为复发性HLH。尽管经过强化治疗后他康复了，但认知功能下降。回顾性分析显示，与非发作期相比，急性失代偿期血清铁蛋白水平更高。相关性分析显示血清铁蛋白与丙酰肉碱（主要的丙酰辅酶A衍生代谢物之一）之间存在密切关系。
HLH是甲基丙二酸血症中一种罕见且未得到充分认识的血液学急症，其早期诊断和治疗至关重要。血清铁蛋白可能是诊断甲基丙二酸血症中与HLH相关发作的有用临床生物标志物。
