Dr.Akshay Kishore , Dr.Bhanu Vikraman Pillai , Dr.Praveena N Bhaskaran , DrCJayakumar Amrita Institute of medical sciences
Two year old female child , 4th child of NCM , Term/AGA with a sibling death with ?suspected liver disease came with complaints of fever, cough and lethargy of 2 days duration.
Associated with non bilious vomiting – 5-6 episodes. On day 2 she had 2 episodes of Generalised seizure lasting for 5 minutes duration. Alteration of sensorium was also present. No history of fast breathing , cyanosis , abdominal distension. She was admitted in the PICU.
On examination ,
Vitals were stable.
There was dolicocephaly with upturned nose. Auxology revealed all parameters were below the 3rd centile. Systemic examination revealed hepatomegaly 2 cm below the right the costal margin. No splenomegaly. CNS examination revealed hypotonia with sluggish reflex.
Differential diagnosis considered were
1.Viral fever
2. Hepatitis A
3. Hypoglycaemic seizures
4. Metabolic / genetic cause
Investigations revealed normal counts with negative CRP. GRBS was low and was corrected as per protocol. ABG didn’t not reveal any acidosis. Total serum bilirubin was normal. AST /ALP – 2500/3000 with INR of 2.9.
Lactate/Ammonia/Electrolytes were normal. Inj.Vitamin K was given and IV Nacetyl cystein (NAC)infusion infusion was started at dose of 100mg/kg/day.
Dengue/Lepto/Widal were negative. Hepatitis panel was negative. Respiratory viral panel showed influenza A positive. Neurological evaluation showed normal EEG with normal MRI. Childs sensorium got better after 2 days and was shifted to ward. Repeat LFT showed improvement.
In view of a sibling death with suspected liver disease , dysmorphism , unexplained transminitis and encephalopathy with fever , a possibility of genetic mutation was considered. Genetic test was done which showed heterozygous mutation of Neuroblastoma amplification sequence(NBAS) gene.
Child improved with NAC infusion
Discussion :
Neuroblastoma amplified sequence (NBAS) gene mutation or infantile liver failure syndrome type 2 (ILFS type 2) is an extremely rare disease characterized episodic liver failure precipitated intercurrent febrile illness, and liver function recovering completely.
The differential diagnoses of any infant presenting with recurrent liver failure or hepatitis includes
Autoimmune hepatitis,
Wolcott–Rallison syndrome,
Perforin deficiency,
Fatty acid oxidation defects,
Mitochondrial hepatopathy,
Dihydrolipoamide dehydrogenase deficiency, and other inborn errors of metabolic liver disease.
NBAS mutation is a rare condition, with only 16 cases reported in the literature. They showed that phenotypic spectrum of NBAS deficiency ranges between isolated recurrent acute liver failure and multisystemic disease, which includes short stature, skeletal dysplasia, optic atrophy, and immunological abnormalities.
Liver crises of NBAS mutation are usually triggered febrile illness and complete recovery is typical between the attacks. Hepatic phenotype episodes usually start with massive increase in alanine transaminase (ALT) and aspartate transaminase (AST), followed severe coagulopathy and mild-to-moderate jaundice.
Cardiomyopathy, autoimmune gastrointestinal disease, and epilepsy can be associated. Treatment is symptomatic with antipyretics , NAC and other supportive measures. Liver transplant was performed in one patient aged 3 years; no further crisis occurred after liver transplant
Take home message : Fever with unexplained acute liver failure think of NBAS mutation.