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Neutral lipid storage myopathy(NLSDM)

MedGen UID:
339913
Concept ID:
C1853136
Disease or Syndrome
Synonyms: Neutral lipid storage disease with myopathy; Neutral lipid storage disease without ichthyosis; NLSDM
SNOMED CT: Neutral lipid storage disease without ichthyosis (699315005); Neutral lipid storage disease with myopathy (699315005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): PNPLA2 (11p15.5)
 
Monarch Initiative: MONDO:0012545
OMIM®: 610717
Orphanet: ORPHA98908

Definition

Neutral lipid storage disease with myopathy (NLSDM) 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). [from OMIM]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/neutral-lipid-storage-disease-with-myopathy

Clinical features

From HPO
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Chronic pancreatitis
MedGen UID:
101753
Concept ID:
C0149521
Disease or Syndrome
A chronic form of pancreatitis.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Increased muscle lipid content
MedGen UID:
373292
Concept ID:
C1837262
Finding
An abnormal accumulation of lipids in skeletal muscle.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeutral lipid storage myopathy
Follow this link to review classifications for Neutral lipid storage myopathy in Orphanet.

Professional guidelines

PubMed

Mai A, Voigt K, Schübel J, Gräßer F
BMC Med Inform Decis Mak 2023 May 9;23(1):89. doi: 10.1186/s12911-023-02170-y. PMID: 37161441Free PMC Article

Recent clinical studies

Etiology

Shahriyari H, Ramezani M, Nilipour Y, Okhovat AA, Kariminejad A, Aghaghazvini L, Fatehi F, Nafissi S
Neuromuscul Disord 2024 Feb;35:19-24. Epub 2023 Dec 21 doi: 10.1016/j.nmd.2023.12.012. PMID: 38194732
Han J, Lu S, Song X, Jı G, Xıe Y, Wu H
Turk J Med Sci 2022 Aug;52(4):1256-1265. Epub 2022 Aug 10 doi: 10.55730/1300-0144.5431. PMID: 36326420Free PMC Article
Angelini C
Biochim Biophys Acta 2015 Apr;1852(4):615-21. Epub 2014 Jul 2 doi: 10.1016/j.bbadis.2014.06.031. PMID: 24997454

Diagnosis

Shahriyari H, Ramezani M, Nilipour Y, Okhovat AA, Kariminejad A, Aghaghazvini L, Fatehi F, Nafissi S
Neuromuscul Disord 2024 Feb;35:19-24. Epub 2023 Dec 21 doi: 10.1016/j.nmd.2023.12.012. PMID: 38194732
Han J, Lu S, Song X, Jı G, Xıe Y, Wu H
Turk J Med Sci 2022 Aug;52(4):1256-1265. Epub 2022 Aug 10 doi: 10.55730/1300-0144.5431. PMID: 36326420Free PMC Article
Reilich P, Horvath R, Krause S, Schramm N, Turnbull DM, Trenell M, Hollingsworth KG, Gorman GS, Hans VH, Reimann J, MacMillan A, Turner L, Schollen A, Witte G, Czermin B, Holinski-Feder E, Walter MC, Schoser B, Lochmüller H
J Neurol 2011 Nov;258(11):1987-97. Epub 2011 May 5 doi: 10.1007/s00415-011-6055-4. PMID: 21544567

Therapy

Han J, Lu S, Song X, Jı G, Xıe Y, Wu H
Turk J Med Sci 2022 Aug;52(4):1256-1265. Epub 2022 Aug 10 doi: 10.55730/1300-0144.5431. PMID: 36326420Free PMC Article

Prognosis

Han J, Lu S, Song X, Jı G, Xıe Y, Wu H
Turk J Med Sci 2022 Aug;52(4):1256-1265. Epub 2022 Aug 10 doi: 10.55730/1300-0144.5431. PMID: 36326420Free PMC Article

Clinical prediction guides

Han J, Lu S, Song X, Jı G, Xıe Y, Wu H
Turk J Med Sci 2022 Aug;52(4):1256-1265. Epub 2022 Aug 10 doi: 10.55730/1300-0144.5431. PMID: 36326420Free PMC Article
Angelini C, Nascimbeni AC, Cenacchi G, Tasca E
Biochim Biophys Acta 2016 Jul;1862(7):1367-73. Epub 2016 Apr 13 doi: 10.1016/j.bbadis.2016.04.008. PMID: 27085974Free PMC Article

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