Neutral lipid storage disease (also known as Chanarin–Dorfman syndrome) is a congenital autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes (Jordans' anomaly),[1] muscle, liver, fibroblasts, and other tissues.

Both subtypes are autosomal recessive disorders, meaning that a mutant allele must be inherited from both parents in order to cause disease.

[citation needed] Subtype I: Neutral Lipid Storage Disease with Myopathy (NLSD-M), is caused by a mutation in the PNPLA2 gene, which reduces the normal expression or function of the ATGL protein.

[citation needed] Subtype II: Neutral Lipid Storage Disease with Ichthyosis (NLSD-I), or Chanarin-Dorfman syndrome, is caused by a mutation in the CGI-58 protein.

In individuals with NLSD, their triglycerides are not catabolized in the blood, and cells accumulate partially processed lipid droplets over time, which may lead to dysfunction in absorbing tissues.

In affected individuals, muscle cells, fibroblasts, and leukocytes appear to be prone to the excessive accumulation of triglycerides as lipid droplets.

Excessive accumulation of lipids in tissues not designed for long-term storage may underlie the clinical manifestations of weakened skeletal and cardiac muscle, fatty liver, pancreatitis, hypothyroidism, and type 2 diabetes.

[citation needed] Main physical signs include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), type 2 diabetes, abnormal levels of creatine kinase in blood, and increased weakness of proximal muscles due to fatty replacement of skeletal muscle fibers.

[9] Specifically, asymmetric right shoulder weakness is an idiosyncratic hallmark of NLSD enabling it to be distinguished from myopathies arising from alternative muscular disorders.

Medium-chain fatty acids in an individual's diet are rapidly used by the body, limiting storage and therefore alleviating lipid droplet accumulation.

[citation needed] The rarity and likely under-diagnosis of neutral lipid storage disease prevents an accurate epidemiological estimate of its frequency in human populations.

[14] Now, having lipid deposits in the white blood cells of the individual is known and recognized as Jordans' anomaly, due to the medical professional who discovered it.

[10] The first case of neutral lipid storage disease was reported by Maurice Dorfman when he treated two sisters with non-bullous ichthyosiform erythroderma in 1974.