Saito Tomoki, Soma Kento, Kashisaka Mai, Iketani Kiiko, Matsumoto Masaaki, Ueda Takuya, Nishiyama Masahiro, Maruyama Azusa, Nakai Ryosuke, Sakihama Hiroshi, Kurosawa Hiroshi, Morisada Naoya, Kobayashi Hironori, Ozaki Kayo
Department of Endocrinology and Metabolism Hyogo Prefectural Kobe Children's Hospital Kobe Japan.
Department of Neurology Hyogo Prefectural Kobe Children's Hospital Kobe Japan.
JIMD Rep. 2025 Apr 4;66(3):e70014. doi: 10.1002/jmd2.70014. eCollection 2025 May.
Systemic primary carnitine deficiency (SPCD) is a rare congenital fatty acid metabolism disorder causing impaired β-oxidation and energy production, leading to hypoglycemia, metabolic encephalopathy, and sudden death. Early diagnosis and treatment, including L-carnitine supplementation and fasting avoidance, can improve prognosis. However, newborn screening (NBS) criteria differ by region, and standardized guidelines are lacking. This report presents a case of SPCD undetected by NBS, resulting in basal ganglia damage and dystonia due to metabolic decompensation. A 1-year-9-month-old girl with no abnormalities on NBS presented with impaired consciousness. She exhibited hypoketotic hypoglycemia, hyperammonemia, and myocardial hypertrophy. Suspecting a fatty acid metabolism disorder, L-carnitine and high-calorie infusion were initiated. Laboratory tests revealed markedly low serum total and free carnitine levels, and genetic analysis confirmed a homozygous mutation. Brain MRI on day 7 revealed bilateral basal ganglia and substantia nigra abnormalities. The patient developed severe dystonia and respiratory failure, requiring ECMO management. L-DOPA was initiated on day 62, resulting in improvements in dystonia, swallowing, and motor function. By day 88, MRI showed resolution of basal ganglia abnormalities, though cerebral atrophy persisted. Basal ganglia damage is a rare but severe SPCD complication. L-DOPA may alleviate dystonia by acting on dopaminergic neurons in the substantia nigra. Early ketone measurement during emergencies is crucial for diagnosing fatty acid metabolism disorders. A standardized NBS protocol with a defined carnitine cutoff value is essential for early detection and prevention of SPCD complications.
全身性原发性肉碱缺乏症（SPCD）是一种罕见的先天性脂肪酸代谢紊乱疾病，可导致β-氧化和能量产生受损，进而引发低血糖、代谢性脑病和猝死。早期诊断和治疗，包括补充左旋肉碱和避免禁食，可改善预后。然而，新生儿筛查（NBS）标准因地区而异，且缺乏标准化指南。本报告介绍了一例NBS未检测出的SPCD病例，该病例因代谢失代偿导致基底神经节损伤和肌张力障碍。一名1岁9个月大的女孩在NBS检查中未发现异常，出现意识障碍。她表现为低酮性低血糖、高氨血症和心肌肥厚。怀疑患有脂肪酸代谢紊乱，开始给予左旋肉碱和高热量输注。实验室检查显示血清总肉碱和游离肉碱水平明显降低，基因分析证实存在纯合突变。第7天的脑部MRI显示双侧基底神经节和黑质异常。患者出现严重肌张力障碍和呼吸衰竭，需要进行体外膜肺氧合（ECMO）治疗。第62天开始使用左旋多巴，肌张力障碍、吞咽和运动功能有所改善。到第88天，MRI显示基底神经节异常消失，尽管脑萎缩仍然存在。基底神经节损伤是一种罕见但严重的SPCD并发症。左旋多巴可能通过作用于黑质中的多巴胺能神经元来缓解肌张力障碍。紧急情况下早期检测酮体对于诊断脂肪酸代谢紊乱至关重要。具有明确肉碱临界值的标准化NBS方案对于早期发现和预防SPCD并发症至关重要。
