MCID: NTR007
MIFTS: 37

Neutral Lipid Storage Disease with Myopathy

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Cardiovascular diseases

Aliases & Classifications for Neutral Lipid Storage Disease with Myopathy

MalaCards integrated aliases for Neutral Lipid Storage Disease with Myopathy:

Name: Neutral Lipid Storage Disease with Myopathy 54 50 24 25 71 29 13 69
Nlsdm 50 24 25 56 71
Neutral Lipid Storage Disease Without Ichthyosis 50 25 71
Neutral Lipid Storage Disease with Myopathy Without Ichthyosis 56
Neutral Lipid Sorage Disease Without Ichthyosis 24
Triglyceride Storage Disease with Ichthyosis 69
Triglyceride Deposit Cardiomyovasculopathy 56
Neutral Lipid Storage Myopathy 56

Characteristics:

Orphanet epidemiological data:

56
neutral lipid storage myopathy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
slowly progressive
adult onset
cardiomyopathy may develop later in the disease
heterozygous mutation carriers may show mild symptoms


HPO:

32
neutral lipid storage disease with myopathy:
Onset and clinical course variable expressivity adult onset slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Neutral Lipid Storage Disease with Myopathy

OMIM : 54
Neutral lipid storage disease with myopathy is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011). Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS; 275630) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007). (610717)

MalaCards based summary : Neutral Lipid Storage Disease with Myopathy, also known as nlsdm, is related to lipidosis with triglycerid storage disease and myopathy, and has symptoms including short stature, hypertriglyceridemia and hepatomegaly. An important gene associated with Neutral Lipid Storage Disease with Myopathy is PNPLA2 (Patatin Like Phospholipase Domain Containing 2). The drugs Bezafibrate and Clofibric Acid have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and skin.

NIH Rare Diseases : 50 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. there is currently no treatment to correct the underlying metabolic problem. last updated: 5/8/2014

UniProtKB/Swiss-Prot : 71 Neutral lipid storage disease with myopathy: Neutral lipid storage disorder (NLSD) with myopathy but without ichthyosis. NLSDs are characterized by the presence of triglyceride- containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Individuals with NLSDM did not show obesity, in spite of a defect in triglyceride degradation in fibroblasts and in marked triglyceride storage in liver, muscles, and other visceral cells.

Genetics Home Reference : 25 Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. People with this condition have muscle weakness (myopathy) due to the accumulation of fats in muscle tissue. Other features of this condition may include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), and type 2 diabetes mellitus (the most common form of diabetes). Signs and symptoms of neutral lipid storage disease with myopathy vary greatly among affected individuals.

Related Diseases for Neutral Lipid Storage Disease with Myopathy

Diseases related to Neutral Lipid Storage Disease with Myopathy via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 lipidosis with triglycerid storage disease 11.1
2 myopathy 10.5
3 lipid storage disease 10.5

Symptoms & Phenotypes for Neutral Lipid Storage Disease with Myopathy

Symptoms via clinical synopsis from OMIM:

54

Muscle Soft Tissue:
hypotonia
muscle pain
myopathy
easy fatigability
difficulty running
more
Laboratory- Abnormalities:
increased serum creatine kinase
abnormal liver enzymes
accumulation of neutral lipids (triglycerides) in leukocytes, muscle cells, fibroblasts, and cardiomyocytes
lipid vacuoles in leukocytes (jordan bodies)
increased serum triglycerides (in some patients)

Cardiovascular- Heart:
cardiomyopathy (in some patients)

Head And Neck- Ears:
hearing loss, sensorineural (in some patients)

Head And Neck- Neck:
neck muscle weakness (in some patients)

Neurologic- Central Nervous System:
delayed walking (rare)

Growth- Height:
short stature (in some patients)

Abdomen- Liver:
abnormal liver enzymes
hepatic steatosis
hepatomegaly (in some patients)

Endocrine Features:
diabetes mellitus (in some patients)

Neurologic- Peripheral Nervous System:
areflexia (in some patients)

Skin Nails & Hair- Skin:
no ichthyosis


Clinical features from OMIM:

610717

Human phenotypes related to Neutral Lipid Storage Disease with Myopathy:

32 (show all 22)
id Description HPO Frequency HPO Source Accession
1 short stature 32 occasional (7.5%) HP:0004322
2 hypertriglyceridemia 32 occasional (7.5%) HP:0002155
3 hepatomegaly 32 HP:0002240
4 gowers sign 32 HP:0003391
5 exercise intolerance 32 HP:0003546
6 areflexia 32 occasional (7.5%) HP:0001284
7 cardiomyopathy 32 occasional (7.5%) HP:0001638
8 myopathy 32 HP:0003198
9 myalgia 32 HP:0003326
10 easy fatigability 32 HP:0003388
11 hepatic steatosis 32 HP:0001397
12 neck muscle weakness 32 occasional (7.5%) HP:0000467
13 diabetes mellitus 32 occasional (7.5%) HP:0000819
14 proximal muscle weakness 32 HP:0003701
15 muscular hypotonia 32 HP:0001252
16 difficulty running 32 HP:0009046
17 difficulty walking 32 HP:0002355
18 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
19 fasciculations 32 HP:0002380
20 elevated hepatic transaminases 32 HP:0002910
21 elevated serum creatine phosphokinase 32 HP:0003236
22 increased muscle lipid content 32 HP:0009058

UMLS symptoms related to Neutral Lipid Storage Disease with Myopathy:


ataxia, muscle weakness, muscular fasciculation, myalgia

Drugs & Therapeutics for Neutral Lipid Storage Disease with Myopathy

Drugs for Neutral Lipid Storage Disease with Myopathy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Bezafibrate Approved Phase 4 41859-67-0 39042
2 Clofibric Acid Phase 4 882-09-7
3 Hypolipidemic Agents Phase 4
4 Anticholesteremic Agents Phase 4
5 Lipid Regulating Agents Phase 4
6 Antimetabolites Phase 4
7 Pharmaceutical Solutions

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM) Completed NCT01527318 Phase 4 Fibrate treatment
2 Clinical Study on the Safety of CNT-02 for TGCV and NLSD-M Recruiting NCT02830763
3 International Registry Study of Neutral Lipid Storage Disease (NLSD) / Triglyceride Deposit Cardiomyovasculopathy (TGCV) and Related Diseases Recruiting NCT02918032
4 Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy Recruiting NCT02635269

Search NIH Clinical Center for Neutral Lipid Storage Disease with Myopathy

Genetic Tests for Neutral Lipid Storage Disease with Myopathy

Genetic tests related to Neutral Lipid Storage Disease with Myopathy:

id Genetic test Affiliating Genes
1 Neutral Lipid Storage Disease with Myopathy 29 24 PNPLA2

Anatomical Context for Neutral Lipid Storage Disease with Myopathy

MalaCards organs/tissues related to Neutral Lipid Storage Disease with Myopathy:

39
Liver, Bone, Skin, Bone Marrow, Pancreas, Heart, Thyroid

Publications for Neutral Lipid Storage Disease with Myopathy

Articles related to Neutral Lipid Storage Disease with Myopathy:

(show all 13)
id Title Authors Year
1
Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation. ( 26600210 )
2016
2
Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings. ( 25956450 )
2015
3
Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy. ( 27896096 )
2014
4
Muscle mri in neutral lipid storage disease with myopathy carrying mutation c.187+1G>A. ( 25363365 )
2014
5
A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review. ( 24836204 )
2014
6
Neutral lipid storage disease with myopathy: a whole-body nuclear MRI and metabolic study. ( 23333026 )
2013
7
Metabolic consequences of adipose triglyceride lipase deficiency in humans: an in vivo study in patients with neutral lipid storage disease with myopathy. ( 23824421 )
2013
8
Effects of bezafibrate treatment in a patient and a carrier with mutations in the PNPLA2 gene, causing neutral lipid storage disease with myopathy. ( 23449549 )
2013
9
Novel PNPLA2 gene mutations in Chinese Han patients causing neutral lipid storage disease with myopathy. ( 22832386 )
2012
10
A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy. ( 22964912 )
2012
11
A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles. ( 21073837 )
2010
12
Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy. ( 18952067 )
2008
13
The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. ( 17187067 )
2007

Variations for Neutral Lipid Storage Disease with Myopathy

UniProtKB/Swiss-Prot genetic disease variations for Neutral Lipid Storage Disease with Myopathy:

71
id Symbol AA change Variation ID SNP ID
1 PNPLA2 p.Pro195Leu VAR_032995 rs121918259

ClinVar genetic disease variations for Neutral Lipid Storage Disease with Myopathy:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 PNPLA2 NM_020376.3(PNPLA2): c.808delC (p.His270Thrfs) deletion Pathogenic rs796065303 GRCh37 Chromosome 11, 823744: 823744
2 PNPLA2 NM_020376.3(PNPLA2): c.584C> T (p.Pro195Leu) single nucleotide variant Pathogenic rs121918259 GRCh37 Chromosome 11, 822494: 822494
3 PNPLA2 NM_020376.3(PNPLA2): c.847delC (p.Gln283Lysfs) deletion Pathogenic rs796065304 GRCh37 Chromosome 11, 823783: 823783
4 PNPLA2 NM_020376.3(PNPLA2): c.865C> T (p.Gln289Ter) single nucleotide variant Pathogenic rs121918260 GRCh37 Chromosome 11, 823801: 823801
5 PNPLA2 NM_020376.3(PNPLA2): c.757+2T> C single nucleotide variant Pathogenic rs777539013 GRCh37 Chromosome 11, 823589: 823589
6 PNPLA2 NM_020376.3(PNPLA2): c.749A> C (p.Gln250Pro) single nucleotide variant Pathogenic rs397514625 GRCh37 Chromosome 11, 823579: 823579
7 PNPLA2 NM_020376.3(PNPLA2): c.757+1G> T single nucleotide variant Pathogenic rs869320738 GRCh37 Chromosome 11, 823588: 823588
8 PNPLA2 NM_020376.3(PNPLA2): c.467delC (p.Pro156Leufs) deletion Pathogenic rs796065307 GRCh37 Chromosome 11, 822004: 822004
9 PNPLA2 NM_020376.3(PNPLA2): c.613dupC (p.Leu205Profs) duplication Pathogenic rs796065308 GRCh37 Chromosome 11, 822523: 822523
10 PNPLA2 NM_020376.3(PNPLA2): c.543delC (p.Ile182Serfs) deletion Pathogenic rs796065309 GRCh37 Chromosome 11, 822453: 822453
11 PNPLA2 NM_020376.3(PNPLA2): c.475_478dupCTCC (p.Gln160Profs) duplication Pathogenic rs796065310 GRCh38 Chromosome 11, 822012: 822015

Expression for Neutral Lipid Storage Disease with Myopathy

Search GEO for disease gene expression data for Neutral Lipid Storage Disease with Myopathy.

Pathways for Neutral Lipid Storage Disease with Myopathy

GO Terms for Neutral Lipid Storage Disease with Myopathy

Sources for Neutral Lipid Storage Disease with Myopathy

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10 dbSNP
11 DGIdb
16 ExPASy
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59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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