Characterization of liver involvement in defects of cholesterol biosynthesis: Long-term follow-up and review

Massimiliano Rossi, Pietro Vajro, Raffaele Iorio, Antonella Battagliese, Nicola Brunetti-Pierri, Gaetano Corso, Maja Di Rocco, Paola Ferrari, Francesco Rivasi, Raffaella Vecchione, Generoso Andria, Giancarlo Parenti

Research output: Contribution to journalArticlepeer-review


Inborn defects of cholesterol biosynthesis are a group of metabolic disorders presenting with mental retardation and multiple congenital anomalies (MCA/MR syndromes). Functional and structural liver involvement has been reported as a rare (2.5-6%) complication of the Smith-Lemli-Opitz syndrome (SLOS) (OMIM: #270400) and it has not been fully characterized. Here, we report on a long-term follow-up study of four patients with SLOS, and one case with lathosterolosis (OMIM: #607330) who presented with liver disease and underwent an extensive diagnostic work-up. Reports of liver involvement in cholesterol biosynthesis defects are reviewed. Two main different patterns of liver involvement emerged: progressive cholestasis, and stable isolated hypertransaminasemia. In our series, the first pattern was found in two patients with SLOS and one with lathosterolosis, and the second in two SLOS cases. Cholestasis was associated with early lethality and normal serum γ-glutamyl-transferase (GGT) levels in SLOS, while possible prolonged survival and high GGT levels were seen in lathosterolosis. Hepatic fibrosis was present in both conditions. Liver biopsy performed in one of our SLOS patients with isolated hypertransaminasemia, showed only mild hydropic degeneration of the hepatocytes. The presence of liver involvement in 16% of the SLOS patients diagnosed at our Center suggests that this complication might have been underestimated in previously reported cases, possibly overshadowed by the severity of multiple malformations. Fetal hepatopathy, cholestasis, and isolated hypertransaminasemia can occur also in other disorders of cholesterol biosynthesis, such as mevalonic aciduria (OMIM: +251170), desmosterolosis (OMIM: #602398), Conradi-Hünermann syndrome (OMIM: #302960), Greenberg dysplasia (OMIM: #215140), and Pelger-Huët homozygosity syndrome (#169400). This group of inherited disorders should be considered in the differential diagnosis of patients presenting with liver disease associated with developmental delay and/or multiple malformations. Periodic liver function evaluations are recommended in these patients.

Original languageEnglish
Pages (from-to)144-151
Number of pages8
JournalAmerican Journal of Medical Genetics
Volume132 A
Issue number2
Publication statusPublished - Jan 15 2005


  • Cholestasis
  • Cholesterol biosynthesis defects
  • Gamma-glutamyl-transferase
  • GGT
  • Lathosterolosis
  • Liver
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Genetics(clinical)


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