Peters Bianca, Schlieben Lea Dewi, Brennenstuhl Heiko, Arikan Cigdem, Bedoyan Sarah M, Bulut Fatma Derya, Crushell Ellen, Dionisi-Vici Carlo, Drab Ada, Fichtner Alexander, Garcia Aixa Gonzalez, Fry Deanna, Garbade Sven F, Hammann Nicole, Hadzic Nedim, Hegarty Robert, Jørgensen Marianne Hørby, Laaß Martin, Lainka Elke, Leghlam Lina, Lurz Eberhard, Mungan Halise Neslihan Önenli, Pietrobattista Andrea, Polo Begona, Socha Piotr, Squires James E, Sun Tian, Vogel Georg F, Prokisch Holger, Kölker Stefan, Hoffmann Georg F, Staufner Christian, Lenz Dominic
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University, Heidelberg, Germany.
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
Liver Int. 2025 Jul;45(7):e70146. doi: 10.1111/liv.70146.
Since described in 2015, NBAS-associated disease has emerged as an important cause of acute liver failure (ALF) in children. We analysed the variable expression, genotype-phenotype association, outcome and prognostic factors of the hepatic involvement.
Individuals with biallelic pathogenic NBAS variants were recruited within an international observational study, including new and previously published patients.
We studied 230 individuals, including 13 previously unreported patients. The liver was the most frequently affected organ (63.4%), with 41.3% experiencing at least one ALF. The median age at onset was 0.9 years, the median age at last ALF 5 years, the latest ALF occurred at 24 years. Liver crises were triggered by febrile infections and presented with highly increased hepatic transaminases. Liver involvement varied significantly between the subgroups: 91.7% of patients with infantile liver failure syndrome type 2 and 88.9% of patients from the combined subgroup (variants affecting β-propeller domain) presented with ALF, whereas SOPH (stature, optic atrophy, Pelger-Huët anomaly) patients mostly had either no liver involvement (66.4%) or persistently elevated transaminases without ALF (28%). The rate of native liver survival was 83.9%; 16 individuals underwent liver transplantation and 24 died.
Liver abnormalities are common and the leading cause of death in NBAS-associated disease. There is a clear genotype-phenotype association regarding the hepatic involvement. Liver crises occur primarily during infancy; however, early medical attention in case of febrile infections is necessary at all ages. Liver transplantation prevents ALF, but its risks must be weighed against the frequency and severity of liver crises decreasing with age.
自2015年被描述以来，NBAS相关疾病已成为儿童急性肝衰竭（ALF）的重要病因。我们分析了肝脏受累的可变表达、基因型-表型关联、结局及预后因素。
在一项国际观察性研究中招募了具有双等位基因致病性NBAS变异的个体，包括新患者和既往已发表的患者。
我们研究了230例个体，其中包括13例既往未报告的患者。肝脏是最常受累的器官（63.4%），41.3%的患者经历过至少一次ALF。发病的中位年龄为0.9岁，最后一次发生ALF的中位年龄为5岁，最晚一次ALF发生在24岁。肝脏危机由发热性感染引发，表现为肝转氨酶大幅升高。各亚组之间肝脏受累情况差异显著：2型婴儿肝衰竭综合征患者中有91.7%以及联合亚组（影响β-螺旋桨结构域的变异）患者中有88.9%出现ALF，而SOPH（身材矮小、视神经萎缩、Pelger-Huët异常）患者大多无肝脏受累（66.4%）或转氨酶持续升高但无ALF（28%）。原位肝存活率为83.9%；16例患者接受了肝移植，24例死亡。
肝脏异常在NBAS相关疾病中很常见，且是主要死因。肝脏受累存在明确的基因型-表型关联。肝脏危机主要发生在婴儿期；然而，各年龄段在出现发热性感染时均需尽早就医。肝移植可预防ALF，但必须权衡其风险与肝脏危机随年龄增长而降低的频率和严重程度。
