(ILFS1, ILFS2, ILFS3)

Prevalence; 1/1.106. Autosomal recessive transmission.

Three forms have been identified:

-        ILFS1: mutation of the LARS1 gene (5q32) [MIM 615 438]

-        ILFS2: mutation of the NABS gene (2p24.3) (neuroblastoma amplified sequence) [MIM 616 483]. The NBAS gene is co-expressed in excess with the MYC gene in neuroblastoma. The NBAS-coded protein is a component of the synthaxin 18 complex that is a key component of retrograde vesicular transport from Golgi's bodies to the endoplasmic reticulum. This complex is heat-sensitive, which may explain the pathophysiology of the disease. Special phenotype: retrognathia, clinodactyly of the fifth finger, brachydactyly of the toes III and V, diffuse osteopenia, vormian bones or bony structures in the cranial sutures.

-        ILFS3: mutation of the RINT1 gene (7q22.3); in addition: short stature, vertebral abnormalities (hypoplasia, platyspondylia) and dysplasia of the femoral heads [MIM 618 641].

Onset before 2 years of age. Recurrent episodes of acute liver failure occurring during febrile episodes: vomiting, apathy, hypoglycemia, liver encephalopathy, sometimes coma, hepatomegaly. Liver function returns to normal between these episodes, which usually disappear after 4 years of age.

Treatment: symptomatic for acute liver failure, sometimes liver transplantation.

Anesthetic implications: 

check the liver enzymes and hepatic function; aggressive prevention of any febrile episode

References : 

• Cardenas V, DiPaola F, Adams SD, Holtz AM, Ahmad A.
  Acute liver failure secondary to neuroblastoma amplified sequence deficiency.
  J Pediatr 2017; 186: 179-82. 
• Chavany J, Cano A, Roquelaure B, Bourgeois P et al.
  Mutations in NBAS ans SCYL1, genetic causes of recurrent liver failure in children : three case reports and literature review.
  Arch Pediatr 2020 ; 27 : 155-9

Updated July 2020