Yazbeck Nadine, Hanna-Wakim Rima, Noun Dolly, Karam Pascale E
Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Division of Pediatric Infectious Diseases, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Clin Med Insights Pediatr. 2025 Aug 12;19:11795565251340558. doi: 10.1177/11795565251340558. eCollection 2025.
Congenital bile acid synthesis disorder type 1 is an extremely rare disease with around 100 cases identified worldwide. Diagnosis remains challenging for pediatricians in view of the non-specific, variable clinical presentations of cholestasis, fat malabsorption, and liver cirrhosis. Early diagnosis and therapy with cholic acid are crucial to reverse the hepatopathy and prevent fatal outcomes. This paper sheds light on the diagnostic challenges of congenital bile acid synthesis disorder type 1 in a patient with an unusual presentation and a previously unreported mutation in the HSD3B7 gene. Moreover, this report aims to increase awareness of this treatable disorder among pediatricians. A 4-year-old child presented to our Medical Center with splenomegaly, fever, multiple lymphadenopathies, and mild cholestasis without hepatomegaly. History was remarkable for recurrent infections since the age of 3 years. Differential diagnosis included viral infections, malignancies, and inherited metabolic disorders. After an extensive negative work-up, genetic testing by next-generation sequencing identified a previously unreported homozygous disease-causing variant in the HSD3B7 gene, confirming the diagnosis of congenital bile acid synthesis disorder type 1. Suggestive abnormal urinary bile acids metabolites were also identified. Bile acid replacement therapy was initiated with reversal of cholestasis. This case highlights an unusual phenotypic presentation and the diagnostic challenges of an extremely rare disorder of bile acid synthesis. An increased awareness among pediatricians and the use of next-generation sequencing as a first-tier test in the setting of non-specific clinical presentations may shortcut the list of extensive investigations, allowing an early diagnosis of such treatable disorders, thus improving the patients' outcomes.
先天性胆汁酸合成障碍1型是一种极其罕见的疾病，全球已确诊约100例。鉴于胆汁淤积、脂肪吸收不良和肝硬化的临床表现不具特异性且多变，儿科医生的诊断仍具有挑战性。早期诊断并用胆酸进行治疗对于逆转肝病和预防致命后果至关重要。本文揭示了一名表现异常且HSD3B7基因存在此前未报道突变的患者先天性胆汁酸合成障碍1型的诊断难题。此外，本报告旨在提高儿科医生对这种可治疗疾病的认识。一名4岁儿童因脾肿大、发热、多处淋巴结病和轻度胆汁淤积（无肝肿大）前来我院就诊。自3岁起反复感染的病史较为突出。鉴别诊断包括病毒感染、恶性肿瘤和遗传性代谢紊乱。经过广泛的阴性检查后，通过下一代测序进行的基因检测在HSD3B7基因中发现了一个此前未报道的纯合致病变异，从而确诊为先天性胆汁酸合成障碍1型。还发现了提示性的异常尿胆汁酸代谢产物。开始进行胆汁酸替代治疗，胆汁淤积得到逆转。该病例突出了一种不寻常的表型表现以及一种极其罕见的胆汁酸合成障碍的诊断难题。儿科医生提高认识并在非特异性临床表现的情况下将下一代测序用作一线检测方法，可能会缩短广泛检查的清单，从而早期诊断此类可治疗疾病，进而改善患者的预后。
