Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis

Am J Transplant. 2014 Apr;14(4):960-5. doi: 10.1111/ajt.12645. Epub 2014 Mar 12.

Abstract

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Keywords: Autism spectrum disorder; cholestasis; defects of cholesterol biosyntesis; lathosterolosis; liver transplantation.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / prevention & control*
  • Child, Preschool
  • Cholesterol / metabolism
  • Female
  • Humans
  • Intellectual Disability / prevention & control*
  • Liver Transplantation*
  • Magnetic Resonance Imaging
  • Oxidoreductases Acting on CH-CH Group Donors / deficiency*
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Prognosis
  • Steroid Metabolism, Inborn Errors / metabolism
  • Steroid Metabolism, Inborn Errors / surgery*
  • Syndrome

Substances

  • lathosterol
  • Cholesterol
  • Oxidoreductases Acting on CH-CH Group Donors

Supplementary concepts

  • Lathosterolosis