Rare Dermatology News

Disease Profile

Neutral lipid storage disease with myopathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Adult

ageofonset-adult.svg

ICD-10

E75.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

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

rnn-autosomalrecessive.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

no.svg

Other names (AKA)

NLSDM; Neutral lipid storage disease without ichthyosis

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

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

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

      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

          1. 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.
          2. 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.
          3. 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.

          Rare Dermatology News