Two cases of non-alcoholic fatty liver disease caused by biallelic ABHD5 mutations

α/β-Hydrolase Domain (ABHD) Inhibitors as New Potential Therapeutic Options against Lipid-Related Diseases

“…The mutation of ABHD5 gene causes the human Chanarin-Dorfman Syndrome or Neutral Lipid Storage Disease with Ichthyosis (NLSDI), which is a rare autosomal recessive disorder characterized by the presence of intracellular accumulation of triacylglycerol (TG) droplets in many tissues. Multiple organs and tissues are affected by this syndrome, since patients suffering of NLSDI manifest ichthyosis and sometimes liver steatosis with hepatomegaly, muscle weakness (or myopathy), ataxia, neurosensory hearing loss, subcapsular cataracts, nystagmus, strabismus, and mental retardation. , ABHD5 mutation is also related to a rare heritable form of nonalcoholic fatty liver disease (NAFLD), a severe health disease associated with significant morbidity and mortality. , In ABHD5, the nucleophilic serine is substituted by asparagine; therefore, ABHD5 itself is not able to hydrolyze triacylglycerols, but it coactivates adipose triglyceride lipase (ATGL), an important TG hydrolase which catalyzes the formation of glycerol and free fatty acids . Mutations in both ATGL and ABHD5 cause the “neutral lipid storage disease” characterized by massive accumulation of TG in various tissues.…”

“… 40 , 41 ABHD5 mutation is also related to a rare heritable form of nonalcoholic fatty liver disease (NAFLD), a severe health disease associated with significant morbidity and mortality. 42 , 43 In ABHD5, the nucleophilic serine is substituted by asparagine; therefore, ABHD5 itself is not able to hydrolyze triacylglycerols, but it coactivates adipose triglyceride lipase (ATGL), an important TG hydrolase which catalyzes the formation of glycerol and free fatty acids. 44 Mutations in both ATGL and ABHD5 cause the “neutral lipid storage disease” characterized by massive accumulation of TG in various tissues.…”

What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside

“…Monogenic mutations of genes associated with lipid metabolism or transport, such as aldolase B ( ALDOB ), apolipoprotein B ( APOB ), and alpha/beta hydrolase domain-containing proteins ( ABHDs ), have been reported as causes of MASLD in lean individuals. Still, these mutations are uncommon and account for only a small proportion of lean MASLD [ 20 , 21 , 22 ]. The development of MASLD in most lean individuals is potentially explained by the collective polygenic effect of SNPs.…”