Neutral lipid storage diseases (NLSDs) are a rare group of autosomal-recessive metabolic disorders characterized by abnormal fat storage with deposition in multiple organ systems. The diseases are caused by mutations in the PNPLA2 gene resulting in defective cytoplasmic triglyceride degradation and excessive triglyceride droplets that deposit systemically in muscle and multiple organs. NLSD can present with myopathy (NLSDM) or ichthyosis (NLSDI, also known as Chanarin-Dorfman disease) caused by mutations in the ABHD5 gene. Jordans' anomaly, the presence of fat-containing vacuoles in neutrophils and monocytes, can be seen on peripheral smear analysis.

NLSDI is distinguished by ichthyosiform erythroderma, intellectual deficit, vision, auditory, and liver abnormalities, and sometimes psychomotor delay. Cardiomyopathy is less commonly associated with NLSDI, and serum creatine kinase may be normal.

NLSDM presents with signs and symptoms of slowly progressive myopathy or skeletal muscle weakness, pain, and atrophy, hepatomegaly, hypertriglyceridemia, and severe dilated cardiomyopathy that can cause premature death. Other associations include insulin resistance, pancreatitis, hypothyroidism, type 2 diabetes mellitus, and sensorineural deafness. Elevations in serum creatine kinase are often seen.

The incidence of NLSDs is not well established; they are rare diseases. Approximately 50 cases are reported in the published literature of which 3 are NLSDM cases and the remaining are NLSDI cases. Patients live into adulthood, and symptoms may first present in a patient's 30s or 40s.

Management may consist of symptomatic relief and a minimal long-chain fat diet. Treatment studies to reduce circulating triglyceride levels are underway.