Researchers from China presented the case of a 16-year-old girl with Alagille syndrome who had a mutation in the NOTCH2 gene in a new paper published in Clinica Chimica Acta.
NOTCH2 mutations are rarely found in patients with Alagille syndrome, and there is little information available about the clinical and pathological profiles of these patients.
The patient described in this study had recurrent jaundice and abnormal hepatic function from 2 weeks after she was born. She also had butterfly vertebrae, a hallmark of Alagille syndrome, as well as the typical facial features associated with the disease including a prominent forehead, deep-set eyes, a pointed chin, and a straight nose with a bulbous tip.
Read more about Alagille syndrome clinical features
When the researchers analyzed the patient genetically, they found that she had a heterozygous c.5857 C > T variant in the NOTCH2 gene. They then performed a liver biopsy and found that she had cholestasis and fibrosis in the portal area of the liver. This was different from the typical bile duct paucity seen in patients with Alagille syndrome who have a mutation in the JAG1 gene, the main cause of the disease.
The researchers wrote, “Since Alagille patients with NOTCH2 mutations have been rarely reported, our case will highlight the clinical and pathological profiles of these patients.”
They added that people with mutations in the NOTCH2 gene usually have a lower penetrance of clinical features than those with a JAG1 mutation and rarely have the skeletal anomalies and facial features associated with the disease.
“We suggested a routine blood test and liver imaging for the patient,” the researchers wrote. They stated that her liver function improved after 2.5 years of treatment with ursodeoxycholic acid, compound embryonic bovine liver extract tablets, and infusions of human serum albumin.
ShenTu Y, Mi X, Tang D, et al. Alagille syndrome caused by NOTCH2 mutation presented atypical pathological changes. Clin Chim Acta. 2021;521:258-263. doi:10.1016/j.cca.2021.07.026