Neutral lipid storage disease with myopathy

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Disease Profile

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Adult

ICD-10

E75.5

Inheritance

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

NLSDM; Neutral lipid storage disease without ichthyosis

Summary

Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. The accumulation of fats in muscle tissue leads to muscle weakness (myopathy). This condition is caused by mutations in the PNPLA2 gene. It is inherited in an autosomal recessive pattern.^[1] There is currently no treatment to correct the underlying metabolic problem.^[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Fatty replacement of skeletal muscle		0012548
Increased intramyocellular lipid droplets		0012240
Progressive proximal muscle weakness		0009073
Shoulder girdle muscle weakness	Weak shoulder muscles	0003547
30%-79% of people have these symptoms
Abnormal circulating creatine kinase concentration	Abnormal levels of creatine kinase in blood	0040081
Cardiomyopathy	Disease of the heart muscle	0001638
Difficulty running		0009046
Difficulty walking	Difficulty in walking	0002355
Easy fatigability		0003388
Elevated hepatic transaminase	High liver enzymes	0002910
Fasciculations	Muscle twitch	0002380
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Gowers sign		0003391
Hepatic steatosis	Fatty infiltration of liver Fatty liver [ more ]	0001397
Hypertriglyceridemia	Increased triglycerides Increased serum triglycerides Increased plasma triglycerides [ more ]	0002155
Increased lactate dehydrogenase level		0025435
Motor delay		0001270
Myalgia	Muscle ache Muscle pain [ more ]	0003326
Myopathy	Muscle tissue disease	0003198
Pelvic girdle muscle weakness		0003749
Very long chain fatty acid accumulation		0008167
5%-29% of people have these symptoms
Areflexia	Absent tendon reflexes	0001284
Chronic pancreatitis	Chronic pancreas inflammation	0006280
Congestive heart failure	Cardiac failure Cardiac failures Heart failure [ more ]	0001635
Diabetes mellitus		0000819
Foot dorsiflexor weakness	Foot drop	0009027
Generalized limb muscle atrophy	Generalized muscle wasting	0009055
Hand muscle weakness		0030237
Hepatomegaly	Enlarged liver	0002240
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Neck muscle weakness	Floppy neck	0000467
Progressive distal muscle weakness		0009063
Rimmed vacuoles		0003805
Sensorineural hearing impairment		0000407
Short stature	Decreased body height Small stature [ more ]	0004322
1%-4% of people have these symptoms
Cholecystitis	Gallbladder inflammation	0001082
Delayed ability to walk		0031936
Pineal cyst		0012683
Percent of people who have these symptoms is not available through HPO
Adult onset	Symptoms begin in adulthood	0003581
Autosomal recessive inheritance		0000007
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
Exercise intolerance	Decreased ability to exercise Inability to exercise [ more ]	0003546
Increased muscle lipid content	Fat accumulation in muscle fibers Fat deposits in muscle fibers Lipid accumulation in skeletal muscle Skeletal muscle lipid accumulation [ more ]	0009058
Proximal muscle weakness	Weakness in muscles of upper arms and upper legs	0003701
Slow progression	Signs and symptoms worsen slowly with time	0003677
Variable expressivity		0003828

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Cause

Neutral lipid storage disease with myopathy is caused by mutations in the PNPLA2 gene. This gene provides instructions for making an enzyme called adipose triglyceride lipase (ATGL). The ATGL enzyme plays a role in breaking down fats called triglycerides. Triglycerides are an important source of stored energy in cells. These fats must be broken down into simpler molecules called fatty acids before they can be used for energy.^[1]

PNPLA2 gene mutations impair the ATGL enzyme's ability to break down triglycerides, allowing them to accumulate in muscle and tissues throughout the body. This results in the signs and symptoms seen in people with neutral lipid storage disease with myopathy.^[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

To date, there is no treatment for the underlying metabolic problem. Current therapies include adhering to strict dietary guidelines and utilizing treatments focused on the associated symptoms. A recent study suggests that people with this condition may benefit from bezafibrate (a medication used to treat high cholesterol) treatment, particularly with respect to lipid accumulation and fat oxidative capacity.^[3] Additional studies into this therapy are needed.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Foundation for Ichthyosis and Related Skin Types (FIRST)
2616 North Broad Street
Colmar, PA 18915
Toll-free: 1-800-545-3286
Telephone: +1-215-997-9400
E-mail: info@firstskinfoundation.org
Website: https://www.firstskinfoundation.org/

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

DermNetNZ provides information on ichthyosis in general. DermNetNZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated.
Genetics Home Reference (GHR) contains information on Neutral lipid storage disease with myopathy. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Neutral lipid storage disease with myopathy. Click on the link to view a sample search on this topic.

References

Neutral lipid storage disease with myopathy. Genetics Home Reference (GHR). February 2014; https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy. Accessed 5/8/2014.
Fischer J, Negre-Salvayre A, Salvayre R. Neutral lipid storage disease. Orphanet. March 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=165. Accessed 5/8/2014.
van de Weijer et al. Effects of bezafibrate treatment in a patient and a carrier with mutations in the PNPLA2 gene, causing neutral lipid storage disease with myopathy. Circ Res. 2013 Mar 1; 112(5):e51-4. https://circres.ahajournals.org/content/112/5/e51.long. Accessed 5/8/2014.

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