Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
BMC Gastroenterol. 2022 May 9;22(1):227. doi: 10.1186/s12876-022-02310-0.
Patients with acid sphingomyelinase deficiency (ASMD) may be referred to a hepatologist for liver manifestations. This study summarized the liver manifestations of patients with ASMD in the early disease course.
This study enrolled ASMD patients diagnosed by genetic tests between July 2016 and December 2020 in a national pediatric liver center. The significance of low High-density lipoprotein cholesterol (HDL-C) for aid diagnosis of ASMD in infancy was explored by reviewing 160 consecutive infants with liver manifestations, who underwent both genetic tests and lipid profile studies, between January 2020 and December 2020.
A total of 7 patients were diagnosed as ASMD, and 10 known disease-causing variants were identified. Hepatosplenomegaly, elevated transaminases, and liver foam cells were observed in all the 7 patients at age ranging from 4 to 31 months. Low HDL-C was detected in 5 patients, cherry red spot in 4 patients, development delay in 3 patients, and interstitial lung diseases in 1 patient. Three ASMD patients developed cholestasis around 1 month of age, and bilirubin levels normalized at age ranging from 3 to 10 months. They had persistently elevated transaminases and hepatosplenomegaly, and died within 4 years of age. Among the 160 infants with liver manifestations, 125 (78.1%) had low HDL-C. Fifty-four had both low HDL-C and splenomegaly, including 48 cholestatic infants, but only 1 (1.9%, 1/54) infant without cholestasis was diagnosed as ASMD.
ASMD can manifest as neonatal cholestasis in the early disease course. Cholestasis is a pitfall when low HDL-C is used for aid diagnosis of ASMD in infants with splenomegaly.
酸鞘磷脂酶缺乏症（ASMD）患者可能因肝脏表现而被转介至肝病专家就诊。本研究总结了早期疾病病程中 ASMD 患者的肝脏表现。
本研究纳入了 2016 年 7 月至 2020 年 12 月期间在一家全国儿科肝脏中心通过基因检测确诊的 ASMD 患者。通过回顾 2020 年 1 月至 12 月期间因肝脏表现而接受基因检测和血脂谱研究的 160 例连续婴儿，探讨低高密度脂蛋白胆固醇（HDL-C）对婴儿期 ASMD 辅助诊断的意义。
共诊断出 7 例 ASMD 患者，鉴定出 10 种已知的致病变异。7 例患者在 4 至 31 月龄时均表现出肝脾肿大、转氨酶升高和肝脏泡沫细胞。5 例患者存在低 HDL-C，4 例患者存在樱桃红斑，3 例患者存在发育迟缓，1 例患者存在间质性肺病。3 例 ASMD 患者在 1 月龄左右出现胆汁淤积，胆红素水平在 3 至 10 月龄时恢复正常。他们持续存在转氨酶升高和肝脾肿大，在 4 岁内死亡。在 160 例有肝脏表现的婴儿中，125 例（78.1%）存在低 HDL-C。54 例同时存在低 HDL-C 和脾肿大，其中包括 48 例胆汁淤积性婴儿，但仅 1 例（1.9%，54 例中的 1 例）无胆汁淤积的婴儿被诊断为 ASMD。
ASMD 在早期疾病病程中可表现为新生儿胆汁淤积。当低 HDL-C 用于辅助诊断脾肿大的婴儿 ASMD 时，胆汁淤积是一个陷阱。
