Introduction: Inborn errors of primary
bile acid (BA) synthesis are rare autosomal recessive disorders responsible for 1-2% of cases of neonatal
cholestasis. Among them,
cerebrotendinous xanthomatosis (CTX) is caused by mutations in the CYP27A1 gene resulting in the impairment of
sterol 27-hydroxylase enzyme activity. Patients and Methods: Here we present the study on two siblings with neonatal
cholestasis diagnosed with
sterol 27-hydroxylase deficiency. The clinical, biochemical, histological, and molecular presentation at the time of diagnosis and detailed follow-up were described. An extensive overview of the literature regarding patients with
sterol 27-hydroxylase deficiency presenting with neonatal
cholestasis was also provided. Results: Patient 1 presented with
cholestatic jaundice since 10 weeks of age and developed the
end-stage liver disease requiring
liver transplantation at 8 months of age but finally succumbed 3 years post-
transplantation due to
autoimmune hemolytic anemia and multiorgan failure development. Next-generation sequencing performed post mortem, revealed him to be homozygous for the known pathogenic splicing variant c.1184+1G>A in the CYP27A1 gene. Patient 2 (sibling) presented with
cholestatic jaundice since the first day of life. Sanger sequencing of CYP27A1 revealed the same results.
Chenodeoxycholic acid treatment was introduced just after diagnosis, at 4 months of age. Fourteen patients with
sterol 27-hydroxylase deficiency presenting with neonatal
cholestasis were reported in the literature, in most of them presenting as a self-limiting disease. Conclusions: An early recognition and treatment initiation in CTX is essential.