No abstract

Pheochromocytoma multisystem crisis (PMC) is a potentially lethal emergency due to catecholamine secretion. The condition manifests as severe hypertension to intractable cardiogenic shock and has a high mortality rate. This study explored the efficacy and safety of applying chlorpromazine on PMC patients. The study included seven patients (median age, 42 years; range, 14–57 years) diagnosed with pheochromocytoma. Four consecutive PMC patients were admitted to our critical care unit between 2016 and 2020 due to abdominal or waist pain, nausea, and vomiting. Their blood pressure (BP) fluctuated between 200–330/120–200 and 40–70/30–50 mmHg. Chlorpromazine (25 or 50 mg) was injected intramuscularly, followed by continuous intravenous infusion (2–8 mg/h). The patients' BP decreased to 100–150/60–100 mmHg within 1–3 h and stabilized within 3–5 days. Two weeks later, surgical tumor resection was successfully performed in all four patients. Similar clinical outcomes were also obtained in three patients with sporadic PMC reported in the literature who received chlorpromazine treatment, which reduced their BP readings from >200/100 mmHg to 120/70 mmHg. Our observations, combined with sporadic reports, showed that chlorpromazine efficiently controlled PMC. Thus, future studies on the use of chlorpromazine are warranted.

Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed via minigene assays and reverse-transcription PCR. We identified a novel pathogenic mutation (c.8051+1G>C) in the splice site of exon 64 of the FBN1 gene in an MFS-pedigree. This mutation was confirmed to cause two different truncated transcripts (entire exon 64 skipping; partial exon 64 exclusion). We also systematically summarized previously reported transcriptional studies of pathogenic splice-altering mutations in the FBN1 gene to investigate the clinical and transcriptional consequences. In conclusion, we reported for the first time that a splice-altering mutation in the FBN1 gene leads to two abnormal transcripts simultaneously.