title: Acute Liver Failure Meets SOPH Syndrome: A Case Report on an Intermediate Phenotype.
abstract: Acute liver failure (ALF) is a life-threatening condition in the absence of preexisting liver disease in children. The main clinical presentation comprises hepatic dysfunction, elevated liver biochemical values, and coagulopathy. The etiology of ALF remains unclear in most affected children; however, the recent identification of mutations in the neuroblastoma amplified sequence (NBAS) gene in autosomal recessively inherited ALF has shed light on the cause of a subgroup of fever-triggered pediatric ALF episodes. Previously, biallelic mutations in NBAS have been reported to be associated with a syndrome comprising short stature, optic atrophy, and Pelger-Huët anomaly (SOPH) specifically occurring in the Yakut population. No hepatic phenotype has been observed in individuals with this disorder who all carry the homozygous NBAS founder mutation c.5741G>A [p.(Arg1914His)]. We present the case of a 4-year-old girl with the cardinal features of SOPH syndrome: characteristic facial dysmorphism, postnatal growth retardation, delay of bone age, slender long bones, optic atrophy, and Pelger-Huët anomaly. During the first 2 years of her life, a series of infections with episodes of fever were accompanied by elevated liver enzyme levels, but hyperammonemia, hypoglycemia, coagulopathy, or encephalopathy suggestive of acute and severe liver disease were never observed. Whole exome sequencing in the patient revealed compound heterozygosity of the 2 NBAS variants, p.(Arg1914His) and p.(Glu943*). This case highlights the variability of clinical presentation associated with NBAS deficiency. Absence of severe liver problems in this case and SOPH-affected Yakut subjects suggests that individuals carrying the NBAS missense mutation p.(Arg1914His) are less susceptible to developing ALF.
authors.affiliation: Institute of Human Genetics and.
authors.forename: Fanny
authors.initials: F
authors.lastname: Kortüm
authors.affiliation: Klinikum Oldenburg, Zentrum für Kinder- und Jugendmedizin, Neuropädiatrie, Oldenburg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Marquardt
authors.affiliation: Bioinformatics Service Facility, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Center for Bioinformatics, University of Hamburg, Hamburg, Germany.|Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Virus Genomics, Hamburg, Germany; and.
authors.forename: Malik
authors.initials: M
authors.lastname: Alawi
authors.affiliation: Klinikum Oldenburg, Zentrum für Kinder- und Jugendmedizin, Neuropädiatrie, Oldenburg, Germany.
authors.forename: Georg Christoph
authors.initials: GC
authors.lastname: Korenke
authors.affiliation: Praxis für Humangenetik, Bremen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Spranger
authors.affiliation: Institute of Human Genetics and.
authors.forename: Peter
authors.initials: P
authors.lastname: Meinecke
authors.affiliation: Institute of Human Genetics and kkutsche@uke.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kutsche
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D004392:Dwarfism / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D017114:Liver Failure, Acute / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics*; D009896:Optic Atrophy / Q000175:diagnosis / Q000235:genetics*; D010381:Pelger-Huet Anomaly / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome
chemical_list: C117339:NBAS protein, human; D009363:Neoplasm Proteins