Neutral lipid storage disease

Neutral lipid storage disease (NLSD) is a group of rare autosomal recessive inherited metabolic disorders characterized by the systemic accumulation of triglycerides (neutral lipids) in cytoplasmic lipid droplets within various tissues throughout the body. The condition encompasses two main subtypes: Neutral lipid storage disease with myopathy (NLSD-M, also known as Chanarin-Dorfman syndrome variant or NLSD due to ATGL deficiency, caused by mutations in the PNPLA2 gene) and Neutral lipid storage disease with ichthyosis (NLSD-I, also known as Chanarin-Dorfman syndrome, caused by mutations in the ABHD5/CGI-58 gene). Both forms share the hallmark finding of lipid-laden leukocytes (Jordan's anomaly) on peripheral blood smear. NLSD-I is characterized by congenital ichthyosiform erythroderma (non-bullous ichthyosis) present from birth, along with hepatomegaly, liver steatosis, and variable involvement of skeletal muscle, the central nervous system (including intellectual disability and sensorineural hearing loss), eyes (cataracts, nystagmus, strabismus), and growth retardation. NLSD-M primarily presents with progressive skeletal and cardiac myopathy, often manifesting in adulthood, along with hepatic steatosis and elevated creatine kinase levels. Cardiac involvement can include dilated or hypertrophic cardiomyopathy, which may be life-threatening. There is currently no specific curative treatment for neutral lipid storage disease. Management is supportive and multidisciplinary, focusing on the specific organ systems affected. Skin care with emollients and keratolytics is important for ichthyosis in NLSD-I. Cardiac monitoring and management of cardiomyopathy are essential in NLSD-M. Dietary modifications, including medium-chain triglyceride supplementation and fat restriction, have been explored with variable benefit. Physical therapy may help manage myopathy. Bezafibrate has been investigated in some cases of NLSD-M with preliminary positive results, but evidence remains limited. Regular monitoring of liver, cardiac, and muscle function is recommended for all patients.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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