[Clinical analysis of 4 cases of McCune-Albright syndrome presenting with infantile cholestasis]

Objective: To summarize the characteristics and prognosis of infantile cholestasis caused by McCune-Albright syndrome (MAS). Methods: A case series study was conducted. Clinical data was collected and analyzed from four infantile cholestasis cases caused by MAS at Pediatric Liver Center, Children's Hospital of Fudan University from February 2016 to October 2025. Descriptive analysis was performed on their clinical characteristics, biochemical examinations, liver ultrasound, liver histopathology, genetic testing, treatment, and prognosis. Results: Among the 4 children (2 males and 2 females), the age of onset was the neonatal period, and presented with jaundice as the initial symptom. Three cases (case 1-3) had pale stools. Mild hepatomegaly was present in all patients. Biochemical examinations revealed elevated gamma-glutamyl transferase (GGT) levels, which were 124, 128, 78, and 258 U/L, accompanied by severely elevated alanine aminotransferase and aspartate aminotransferase levels, with peak values of 2 312 and 1 742 U/L. Liver histology in case 1 and case 3 at 2 months of age showed cholestasis, fibrous tissue hyperplasia, separation of lobules of liver, mild bile ducts hyperplasiamild. Follow-up liver histopathology in case 1 at 1.3 years of age revealed significant improvement in inflammation and fibrosis. Liver histopathology in case 4 at 3.2 years of age showed mild cholestasis, mild inflammation in the portal areas and reduced number of intrahepatic bile ducts. While the cholestasis subsided spontaneously by approximately 8 months of age, liver transaminase abnormalities could last for several years, and only 1 case (case 3) returned to normal after 1.9 years. Café-au-lait spots were present at birth in 3 cases (case 1, 3, 4) and appeared at 2 months of age in 1 case (case 2). Precocious puberty and bony abnormality occurred later than the onset of cholestasis. The results of whole exon sequencing of blood samples from all the four cases were negative, whereas GNAS variant was identified in the liver tissue of case 4. Conclusions: MAS can involve the liver. In infancy, it can present as high-GGT cholestasis accompanied by severely elevated transaminases. Although jaundice may resolve spontaneously in infants, abnormal transaminase levels can persist. Detection of GNAS variants in liver tissue may facilitate early diagnosis.