SynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyReferences

View all Images (2)

Neutral lipid storage disease
Other Resources UpToDate PubMed

Neutral lipid storage disease

Contributors: Michael W. Winter MD, Nishant H. Patel MD, Desiree Rivera-Nieves MD, Khaled Bittar MD, Paritosh Prasad MD
Other Resources UpToDate PubMed


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.


E75.5 – Other lipid storage disorders

10741005 – Lipid storage disease

Look For

Subscription Required

Diagnostic Pearls

Subscription Required

Differential Diagnosis & Pitfalls

Fatty acid transport disorders:
  • Carnitine palmitoyltransferase 1A deficiency
  • Carnitine acylcarnitine translocase deficiency
  • Carnitine palmitoyltransferase 2 deficiency
Intramitochondrial beta-oxidation defects:
  • Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
  • Medium chain acyl-CoA dehydrogenase (MCAD) deficiency
  • Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
  • Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
  • 3-Hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) deficiency
Muscular dystrophy (eg, Duchenne muscular dystrophy, Becker muscular dystrophy)

Protein-losing enteropathy

Best Tests

Subscription Required

Management Pearls

Subscription Required


Subscription Required


Subscription Required

Last Reviewed:03/06/2018
Last Updated:01/20/2022
Copyright © 2024 VisualDx®. All rights reserved.
Neutral lipid storage disease
A medical illustration showing key findings of Neutral lipid storage disease (NLSD with Myopathy) : Hepatosplenomegaly, Hypotonia, Proximal muscle weakness, Creatine kinase elevated
Copyright © 2024 VisualDx®. All rights reserved.