MCID: NTR007
MIFTS: 35

Neutral Lipid Storage Disease with Myopathy

Categories: Genetic diseases, Rare diseases, Cardiovascular diseases, Neuronal diseases, Metabolic 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 53 49 24 71 36 28 13 69
Nlsdm 53 49 24 55 71
Neutral Lipid Storage Disease Without Ichthyosis 53 49 24 71
Neutral Lipid Storage Disease with Myopathy Without Ichthyosis 55
Triglyceride Storage Disease with Ichthyosis 69
Triglyceride Deposit Cardiomyovasculopathy 55
Neutral Lipid Storage Myopathy 55

Characteristics:

Orphanet epidemiological data:

55
neutral lipid storage myopathy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
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 : 53 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 myalgia, diabetes mellitus and hepatomegaly. An important gene associated with Neutral Lipid Storage Disease with Myopathy is PNPLA2 (Patatin Like Phospholipase Domain Containing 2), and among its related pathways/superpathways is Regulation of lipolysis in adipocytes. The drugs Bezafibrate and Anticholesteremic Agents have been mentioned in the context of this disorder. Affiliated tissues include liver, skin and bone.

Genetics Home Reference : 24 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 (the most common form of diabetes). Signs and symptoms of neutral lipid storage disease with myopathy vary greatly among affected individuals.

NIH Rare Diseases : 49 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.

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:

# Related Disease Score Top Affiliating Genes
1 lipidosis with triglycerid storage disease 11.2
2 myopathy 10.6
3 lipid storage disease 10.6

Symptoms & Phenotypes for Neutral Lipid Storage Disease with Myopathy

Symptoms via clinical synopsis from OMIM:

53
Muscle Soft Tissue:
myopathy
fasciculations
difficulty walking
easy fatigability
hypotonia
more
Growth Height:
short stature (in some patients)

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

Cardiovascular Heart:
cardiomyopathy (in some patients)

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

Neurologic Central Nervous System:
delayed walking (rare)

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

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)

Neurologic Peripheral Nervous System:
areflexia (in some patients)

Endocrine Features:
diabetes mellitus (in some patients)

Skin Nails Hair Skin:
no ichthyosis


Clinical features from OMIM:

610717

Human phenotypes related to Neutral Lipid Storage Disease with Myopathy:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 myalgia 31 HP:0003326
2 diabetes mellitus 31 occasional (7.5%) HP:0000819
3 hepatomegaly 31 HP:0002240
4 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
5 short stature 31 occasional (7.5%) HP:0004322
6 myopathy 31 HP:0003198
7 elevated serum creatine phosphokinase 31 HP:0003236
8 hypertriglyceridemia 31 occasional (7.5%) HP:0002155
9 hepatic steatosis 31 HP:0001397
10 elevated hepatic transaminases 31 HP:0002910
11 cardiomyopathy 31 occasional (7.5%) HP:0001638
12 areflexia 31 occasional (7.5%) HP:0001284
13 fasciculations 31 HP:0002380
14 difficulty walking 31 HP:0002355
15 exercise intolerance 31 HP:0003546
16 proximal muscle weakness 31 HP:0003701
17 generalized hypotonia 31 HP:0001290
18 increased muscle lipid content 31 HP:0009058
19 neck muscle weakness 31 occasional (7.5%) HP:0000467
20 easy fatigability 31 HP:0003388
21 gowers sign 31 HP:0003391
22 difficulty running 31 HP:0009046

UMLS symptoms related to Neutral Lipid Storage Disease with Myopathy:


myalgia, muscular fasciculation, muscle weakness, ataxia

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 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Bezafibrate Approved, Investigational Phase 4 41859-67-0 39042
2 Anticholesteremic Agents Phase 4
3 Antimetabolites Phase 4
4 Clofibric Acid Phase 4 882-09-7
5 Hypolipidemic Agents Phase 4
6 Lipid Regulating Agents Phase 4

Interventional clinical trials:


# 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 International Registry Study of Neutral Lipid Storage Disease (NLSD) / Triglyceride Deposit Cardiomyovasculopathy (TGCV) and Related Diseases Recruiting NCT02918032
3 Clinical Study on the Safety of CNT-02 for TGCV and NLSD-M Enrolling by invitation NCT02830763

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:

# Genetic test Affiliating Genes
1 Neutral Lipid Storage Disease with Myopathy 28 PNPLA2

Anatomical Context for Neutral Lipid Storage Disease with Myopathy

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

38
Liver, Skin, Bone, Bone Marrow, Heart, Thyroid, Pancreas

Publications for Neutral Lipid Storage Disease with Myopathy

Articles related to Neutral Lipid Storage Disease with Myopathy:

(show all 13)
# 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
Muscle mri in neutral lipid storage disease with myopathy carrying mutation c.187+1G>A. ( 25363365 )
2014
4
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
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
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
7
Neutral lipid storage disease with myopathy: a whole-body nuclear MRI and metabolic study. ( 23333026 )
2013
8
Metabolic consequences of adipose triglyceride lipase deficiency in humans: an in vivo study in patients with neutral lipid storage disease with myopathy. ( 23824421 )
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
# 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)
# Gene Variation Type Significance SNP ID Assembly Location
1 PNPLA2 NM_020376.3(PNPLA2): c.757+2T> C single nucleotide variant Pathogenic rs777539013 GRCh37 Chromosome 11, 823589: 823589
2 PNPLA2 NM_020376.3(PNPLA2): c.749A> C (p.Gln250Pro) single nucleotide variant Pathogenic rs397514625 GRCh37 Chromosome 11, 823579: 823579
3 PNPLA2 NM_020376.3(PNPLA2): c.757+1G> T single nucleotide variant Pathogenic rs869320738 GRCh37 Chromosome 11, 823588: 823588
4 PNPLA2 NM_020376.3(PNPLA2): c.467delC (p.Pro156Leufs) deletion Pathogenic rs796065307 GRCh37 Chromosome 11, 822004: 822004
5 PNPLA2 NM_020376.3(PNPLA2): c.613dupC (p.Leu205Profs) duplication Pathogenic rs796065308 GRCh37 Chromosome 11, 822523: 822523
6 PNPLA2 NM_020376.3(PNPLA2): c.543delC (p.Ile182Serfs) deletion Pathogenic rs796065309 GRCh37 Chromosome 11, 822453: 822453
7 PNPLA2 NM_020376.3(PNPLA2): c.475_478dupCTCC (p.Gln160Profs) duplication Pathogenic rs796065310 GRCh38 Chromosome 11, 822012: 822015
8 PNPLA2 NM_020376.3(PNPLA2): c.808delC (p.His270Thrfs) deletion Pathogenic rs796065303 GRCh37 Chromosome 11, 823744: 823744
9 PNPLA2 NM_020376.3(PNPLA2): c.584C> T (p.Pro195Leu) single nucleotide variant Pathogenic rs121918259 GRCh37 Chromosome 11, 822494: 822494
10 PNPLA2 NM_020376.3(PNPLA2): c.847delC (p.Gln283Lysfs) deletion Pathogenic rs796065304 GRCh37 Chromosome 11, 823783: 823783
11 PNPLA2 NM_020376.3(PNPLA2): c.865C> T (p.Gln289Ter) single nucleotide variant Pathogenic rs121918260 GRCh37 Chromosome 11, 823801: 823801

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

Pathways related to Neutral Lipid Storage Disease with Myopathy according to KEGG:

36
# Name Kegg Source Accession
1 Regulation of lipolysis in adipocytes hsa04923

GO Terms for Neutral Lipid Storage Disease with Myopathy

Sources for Neutral Lipid Storage Disease with Myopathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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