Claeyssens Claire, Witters Peter, Segers Heidi, De Koster Jan, Levtchenko Elena, Vermeersch Pieter
Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
Clinical Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
Biochem Med (Zagreb). 2025 Jun 15;35(2):020901. doi: 10.11613/BM.2025.020901.
Neuroblastomas represent a diverse group of neuroblastic tumors characterized by variability in their clinical progression and degree of differentiation. In rare cases, patients with neuroblastoma may present with paraneoplastic syndromes, such as watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome), linked to the secretion of vasoactive intestinal peptide (VIP). We report a case of a 14-month-old girl presented with a three-week history of watery diarrhea and signs of dehydration with no other symptoms. The patient's medical history was unremarkable, and no medication use was reported. Venous blood gas analysis revealed a normal anion gap metabolic acidosis with severe hypokalemia. The patient was referred to our hospital 48 hours post-admission due to persistent hypokalemic metabolic acidosis, unresponsive to intravenous fluid therapy. The primary causes of normal anion gap metabolic acidosis in young children are gastrointestinal bicarbonate loss due to diarrhea and renal bicarbonate loss. Semi-quantitative urine organic acid analysis, reported 48 hours after admission, revealed increased vanillylmandelic acid (VMA) (89 mmol/mol creatinine) and homovanillic acid (HVA) (21 mmol/mol creatinine), raising the suspicion of a neuroblastoma. Subsequent analysis of an acidified urine sample confirmed a more than threefold increase in VMA, HVA, normetanephrine, norepinephrine, and 3-methoxytyramine concentrations. In addition, VIP was markedly elevated (1994 ng/L) in a blood sample. The diagnosis of neuroblastoma was confirmed through imaging and histological examination. This case illustrates that chronic diarrhea with metabolic dysregulation ( hypokalemia) can be the first and only symptom in patients with VIP-secreting neuroblastoma which can result in delayed diagnosis of neuroblastoma.
神经母细胞瘤是一组多样化的神经母细胞肿瘤，其临床进展和分化程度存在差异。在罕见情况下，神经母细胞瘤患者可能会出现副肿瘤综合征，如水样腹泻、低钾血症和无胃酸症（WDHA综合征），这与血管活性肠肽（VIP）的分泌有关。我们报告一例14个月大女童，有三周水样腹泻病史及脱水体征，无其他症状。患者既往病史无异常，未报告用药情况。静脉血气分析显示为正常阴离子间隙代谢性酸中毒伴严重低钾血症。入院48小时后，因持续性低钾血症性代谢性酸中毒对静脉补液治疗无反应，患者被转诊至我院。幼儿正常阴离子间隙代谢性酸中毒的主要原因是腹泻导致的胃肠道碳酸氢盐丢失和肾脏碳酸氢盐丢失。入院48小时后报告的半定量尿有机酸分析显示香草扁桃酸（VMA）（89 mmol/mol肌酐）和高香草酸（HVA）（21 mmol/mol肌酐）增加，怀疑为神经母细胞瘤。随后对酸化尿样的分析证实VMA、HVA、去甲变肾上腺素、去甲肾上腺素和3-甲氧基酪胺浓度增加了三倍多。此外，血样中VIP明显升高（1994 ng/L）。通过影像学和组织学检查确诊为神经母细胞瘤。该病例表明，伴有代谢失调（低钾血症）的慢性腹泻可能是分泌VIP的神经母细胞瘤患者的首发且唯一症状，这可能导致神经母细胞瘤的诊断延迟。
