With the growing obesity epidemic, nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the leading causes of liver disease worldwide. Although obesity is a main risk factor for the development of NAFLD, it can also develop in lean subjects and can be encountered in different clinical setting and in association with an array of genetic, metabolic, nutritional, infectious and drug-induced disorders. Areas covered: This article discusses causes of fatty liver in non-obese subjects focusing on Lysosomal acid lipase deficiency (LAL-D), a commonly overlooked disorder reviewing its prevalence, genetics, pathogenesis, clinical features, diagnosis and treatment. It will also review other causes of non-alcoholic fatty liver disease, which can be encountered in the absence of obesity and metabolic syndrome. Expert commentary: Although the prevalence of LAL-D has been estimated in the range of 1 in 40,000 and 1 in 300,000, this estimate is much more than the identified cases reported in the literature, which suggests that that the disease may be considerably under-diagnosed. There is a pressing need to educate clinicians about the disease, especially with the development of new promising therapeutic modalities.
Keywords: LAL-D; NAFLD; NASH; NOFLD; Nonalcoholic fatty liver disease; lysosomal acid lipase deficiency; metabolic syndrome; obesity.