Dataset Information

Novel neuroblastoma amplified sequence (NBAS) mutations in a Japanese boy with fever-triggered recurrent acute liver failure.

ABSTRACT: Biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene have been reported to cause two different clinical spectra: short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome and infantile liver failure syndrome 2 (ILFS2). Here, we describe a case of a 3-year-old Japanese boy who presented with fever-triggered recurrent acute liver failure (ALF). The clinical characteristics were considerable elevation of liver enzymes, severe coagulopathy, and acute renal failure. In addition to the liver phenotype, he had short stature and Pelger-Huët anomaly in the peripheral granulocytes. Whole-exome and Sanger sequencing of the patient and his parents revealed that he carried novel compound heterozygous missense mutations in NBAS, c.1018G>C (p.Gly340Arg) and c.2674?G>T (p.Val892Phe). Both mutations affect evolutionarily conserved amino acid residues and are predicted to be highly damaging. Immunoblot analysis of the patient's skin fibroblasts showed a normal NBAS protein level but a reduced protein level of its interaction partner, p31, involved in Golgi-to-endoplasmic reticulum retrograde vesicular trafficking. We recommend NBAS gene analysis in children with unexplained fever-triggered recurrent ALF or liver dysfunction. Early antipyretic therapy may prevent further episodes of ALF.

SUBMITTER: Ono S

PROVIDER: S-EPMC6323122 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Novel neuroblastoma amplified sequence (<i>NBAS</i>) mutations in a Japanese boy with fever-triggered recurrent acute liver failure.

Ono Sahoko S Matsuda Junko J Watanabe Etsuko E Akaike Hiroto H Teranishi Hideto H Miyata Ippei I Otomo Takanobu T Sadahira Yoshito Y Mizuochi Tatsuki T Kusano Hironori H Kage Masayoshi M Ueno Hiroo H Yoshida Kenichi K Shiraishi Yuichi Y Chiba Kenichi K Tanaka Hiroko H Miyano Satoru S Ogawa Seishi S Hayashi Yasuhide Y Kanegane Hirokazu H Ouchi Kazunobu K

Human genome variation 20190107

Biallelic mutations in the neuroblastoma amplified sequence (<i>NBAS</i>) gene have been reported to cause two different clinical spectra: short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome and infantile liver failure syndrome 2 (ILFS2). Here, we describe a case of a 3-year-old Japanese boy who presented with fever-triggered recurrent acute liver failure (ALF). The clinical characteristics were considerable elevation of liver enzymes, severe coagulopathy, and acute re ...[more]

PMID: 30622725

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Project description:Pediatric acute-liver-failure due to acetaminophen (APAP) administration at therapeutic dosage is rare, while viral infections and metabolic defects are the prevalent causes. Yet, as acetaminophen is routinely used in febrile illnesses, it may be mistakenly held responsible for the acute liver damage.An 11 month old boy had been on acetaminophen for 10 days (total dose 720 mg = 72 mg/kg) when he developed acute-liver-failure with encephalopathy. As he rapidly improved on N-acetylcysteine (NAC) infusion, it was concluded that chronic acetaminophen administration in an infant had lead to acute-liver-failure even at therapeutic doses, that N-acetylcysteine infusion had been life-saving and should be immediately started in similar circumstances. The child, however, had two further episodes of acute liver damage over a 34-month period, without having been given acetaminophen, as the parents carefully avoided using it. His clinical, laboratory and radiological findings between the acute episodes were unremarkable. His features and skeletal surveys were not suggestive of a syndromic condition. He then went on to suffer another episode of acute-liver-failure with multi-organ failure, necessitating an urgent liver transplant. All efforts to come to a diagnosis for the causes of his recurrent episodes of liver failure had been unsuccessful, until a biallelic mutation in the NBAS gene was reported to be associated with recurrent acute-liver-failure in children. The boy's DNA analysis revealed compound heterozygous pathogenic mutations in the NBAS gene. Liver failure episodes in these patients are triggered and worsened by fever, most likely due to thermal susceptibility of hepatocytes, hence APAP, rather than being a culprit, is part of the supportive treatment.We suggest that, in acute-liver-failure with a history of acetaminophen exposure at therapeutic dosage, clinicians should not be contented with administering NAC, but should consider an alternative etiology, above all if the episodes are recurrent, and actively start supportive and antipyretic treatment while seeking the advice of a specialist unit.

Dataset Information

Novel neuroblastoma amplified sequence (NBAS) mutations in a Japanese boy with fever-triggered recurrent acute liver failure.

Publications

Novel neuroblastoma amplified sequence (<i>NBAS</i>) mutations in a Japanese boy with fever-triggered recurrent acute liver failure.

Similar Datasets

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