Steatotic liver disease associated with 2,4-dienoyl-CoA reductase 1 deficiency

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2024年9月14日

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Benno Kohlmaier,
Kristijan Skok,
Carolin Lackner,
Greta Haselrieder,
Thomas Müller,
Sabrina Sailer,
Johannes Zschocke,
Markus A. Keller,
A. S. Knisely,
Andreas R. Janecke

摘要

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered multifactorial with a number of predisposing gene polymorphisms known.

Methods

The occurrence of MASLD in 7 and 10 year old siblings, one without classical risk factors and one with type 2 diabetes suggested a monogenic etiology and prompted next-generation sequencing. Exome sequencing was performed in the proband, both parents and both siblings. The impact of a likely disease-causing DNA variant was assessed on the transcript and protein level.

Results

Two siblings have hepatomegaly, elevated serum transaminase activity, and steatosis and harbor a homozygous DECR1 splice-site variant, c.330+3A>T. The variant caused DECR1 transcript decay. Immunostaining demonstrated lack of DECR1 in patient liver.

Conclusions

These patients may represent the first individuals with DECR1 deficiency, then defining within MASLD an autosomal-recessive entity, well corresponding to the reported steatotic liver disease in Decr1 knockout mice. DECR1 may need to be considered in the genetic work-up of MASLD.