In what kind of patient scenario would you consider testing for inherited disorders of lipid metabolism in the evaluation of a patient with MASLD?

I usually am concerned about a monogenic cause of MASLD when the patient has steatosis without the traditional metabolic risk factors that we typically see. Additionally, if patients have other features such as severely low LDL in the setting of steatosis, rapidly progressive liver disease, early age of onset, or family history of severe hyperlipidemia/hypertriglyceridemia, then I do consider testing for monogenic causes and refer them to a lipidologist or cardiologist to evaluate and consider genetic testing for familial conditions. I have checked for lysosomal acid lipase deficiency a few times, but haven't caught it yet in my experience. These patients can also get neurological symptoms, which is another sign to watch out for.

I personally start thinking about inherited or monogenic lipid disorders in a MASLD evaluation when the phenotype does not align with the usual metabolic risk pattern.

For me, the main triggers are:

1. Steatosis in the absence of classic metabolic risk factors such as obesity, diabetes, or insulin resistance.
2. Very low LDL-C or ApoB (usually checked by the referring primary care provider) in a patient with clear hepatic steatosis, which raises concern for familial hypobetalipoproteinemia or related disorders.
3. Rapidly progressive liver disease or fibrosis that seems disproportionate to the metabolic profile.
4. Early age of onset, including children, teens, or young adults
5. Strong FH of severe hypercholesterolemia or hypertriglyceridemia, premature...