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Neutral lipid storage disease with myopathy(NLSDM)

MedGen UID:
339913
Concept ID:
C1853136
Disease or Syndrome
Synonyms: Neutral lipid storage disease without ichthyosis; NLSDM
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Neutral lipid storage disease without ichthyosis (699315005); Neutral lipid storage disease with myopathy (699315005)
 
Gene (location): PNPLA2 (11p15.5)
OMIM®: 610717
Orphanet: ORPHA98908

Definition

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). [from OMIM]

Additional description

From GHR
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.  https://ghr.nlm.nih.gov/condition/neutral-lipid-storage-disease-with-myopathy

Clinical features

Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in a muscle or group of muscles.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
Diabetes is a disease in which your blood glucose, or blood sugar, levels are too high. Glucose comes from the foods you eat. Insulin is a hormone that helps the glucose get into your cells to give them energy. With type 1 diabetes, your body does not make insulin. With type 2 diabetes, the more common type, your body does not make or use insulin well. Without enough insulin, the glucose stays in your blood. You can also have prediabetes. This means that your blood sugar is higher than normal but not high enough to be called diabetes. Having prediabetes puts you at a higher risk of getting type 2 diabetes. Over time, having too much glucose in your blood can cause serious problems. It can damage your eyes, kidneys, and nerves. Diabetes can also cause heart disease, stroke and even the need to remove a limb. Pregnant women can also get diabetes, called gestational diabetes. A blood test can show if you have diabetes. Exercise, weight control and sticking to your meal plan can help control your diabetes. You should also monitor your glucose level and take medicine if prescribed. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Sign or Symptom
Enlargement of the liver.
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
Your muscles help you move and help your body work. Different types of muscles have different jobs. There are many problems that can affect muscles. Muscle disorders can cause weakness, pain or even paralysis. . Causes of muscle disorders include. -Injury or overuse, such as sprains or strains, cramps or tendinitis . -A genetic disorder, such as muscular dystrophy. -Some cancers. -Inflammation, such as myositis. -Diseases of nerves that affect muscles. -Infections. -Certain medicines. Sometimes the cause is not known.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Increased muscle lipid content
MedGen UID:
373292
Concept ID:
C1837262
Finding
An abnormal accumulation of lipids in skeletal muscle.
Proximal muscle weakness
MedGen UID:
325534
Concept ID:
C1838869
Sign or Symptom
A lack of strength of the proximal muscles.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
Diabetes is a disease in which your blood glucose, or blood sugar, levels are too high. Glucose comes from the foods you eat. Insulin is a hormone that helps the glucose get into your cells to give them energy. With type 1 diabetes, your body does not make insulin. With type 2 diabetes, the more common type, your body does not make or use insulin well. Without enough insulin, the glucose stays in your blood. You can also have prediabetes. This means that your blood sugar is higher than normal but not high enough to be called diabetes. Having prediabetes puts you at a higher risk of getting type 2 diabetes. Over time, having too much glucose in your blood can cause serious problems. It can damage your eyes, kidneys, and nerves. Diabetes can also cause heart disease, stroke and even the need to remove a limb. Pregnant women can also get diabetes, called gestational diabetes. A blood test can show if you have diabetes. Exercise, weight control and sticking to your meal plan can help control your diabetes. You should also monitor your glucose level and take medicine if prescribed. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Creatine phosphokinase, elevated serum
MedGen UID:
69128
Concept ID:
C0241005
Finding
The caveolinopathies, a group of muscle diseases, can be classified into five phenotypes, which can be seen in different members of the same family: Limb-girdle muscular dystrophy 1C (LGMD1C), characterized by onset usually in the first decade, mild-to-moderate proximal muscle weakness, calf hypertrophy, positive Gower sign, and variable muscle cramps after exercise . Isolated hyperCKemia (i.e., elevated serum concentration of creatine kinase (CK) in the absence of signs of muscle disease) (HCK). Rippling muscle disease (RMD), characterized by signs of increased muscle irritability, such as percussion-induced rapid contraction (PIRC), percussion-induced muscle mounding (PIMM), and/or electrically silent muscle contractions (rippling muscle). Distal myopathy (DM), observed in one individual only Hypertrophic cardiomyopathy (HCM), without skeletal muscle manifestations.
Hypertriglyceridemia
MedGen UID:
279403
Concept ID:
C1522137
Laboratory or Test Result
An abnormal increase in the level of triglycerides in the blood.

Term Hierarchy

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

Recent clinical studies

Etiology

Saunders CJ, Moon SH, Liu X, Thiffault I, Coffman K, LePichon JB, Taboada E, Smith LD, Farrow EG, Miller N, Gibson M, Patterson M, Kingsmore SF, Gross RW
Hum Mutat 2015 Mar;36(3):301-6. doi: 10.1002/humu.22743. PMID: 25512002Free PMC Article
Laforêt P, Stojkovic T, Bassez G, Carlier PG, Clément K, Wahbi K, Petit FM, Eymard B, Carlier RY
Mol Genet Metab 2013 Feb;108(2):125-31. Epub 2012 Dec 28 doi: 10.1016/j.ymgme.2012.12.004. PMID: 23333026
Janssen MC, van Engelen B, Kapusta L, Lammens M, van Dijk M, Fischer J, van der Graaf M, Wevers RA, Fahrleitner M, Zimmermann R, Morava E
Eur J Hum Genet 2013 Aug;21(8):807-15. Epub 2012 Dec 12 doi: 10.1038/ejhg.2012.256. PMID: 23232698Free PMC Article
Lin P, Li W, Wen B, Zhao Y, Fenster DS, Wang Y, Gong Y, Yan C
J Hum Genet 2012 Oct;57(10):679-81. Epub 2012 Jul 26 doi: 10.1038/jhg.2012.84. PMID: 22832386
Fischer J, Lefèvre C, Morava E, Mussini JM, Laforêt P, Negre-Salvayre A, Lathrop M, Salvayre R
Nat Genet 2007 Jan;39(1):28-30. Epub 2006 Dec 24 doi: 10.1038/ng1951. PMID: 17187067

Diagnosis

Massa R, Pozzessere S, Rastelli E, Serra L, Terracciano C, Gibellini M, Bozzali M, Arca M
Muscle Nerve 2016 Apr;53(4):644-8. Epub 2016 Feb 22 doi: 10.1002/mus.24983. PMID: 26600210
Kaneko K, Kuroda H, Izumi R, Tateyama M, Kato M, Sugimura K, Sakata Y, Ikeda Y, Hirano K, Aoki M
Neuromuscul Disord 2014 Jul;24(7):634-41. Epub 2014 Apr 21 doi: 10.1016/j.nmd.2014.04.001. PMID: 24836204
Natali A, Gastaldelli A, Camastra S, Baldi S, Quagliarini F, Minicocci I, Bruno C, Pennisi E, Arca M
J Clin Endocrinol Metab 2013 Sep;98(9):E1540-8. Epub 2013 Jul 3 doi: 10.1210/jc.2013-1444. PMID: 23824421
Laforêt P, Stojkovic T, Bassez G, Carlier PG, Clément K, Wahbi K, Petit FM, Eymard B, Carlier RY
Mol Genet Metab 2013 Feb;108(2):125-31. Epub 2012 Dec 28 doi: 10.1016/j.ymgme.2012.12.004. PMID: 23333026
Ash DB, Papadimitriou D, Hays AP, Dimauro S, Hirano M
Arch Neurol 2012 Sep;69(9):1190-2. doi: 10.1001/archneurol.2011.2600. PMID: 22964912Free PMC Article

Therapy

Tavian D, Missaglia S, Redaelli C, Pennisi EM, Invernici G, Wessalowski R, Maiwald R, Arca M, Coleman RA
Hum Mol Genet 2012 Dec 15;21(24):5318-28. Epub 2012 Sep 17 doi: 10.1093/hmg/dds388. PMID: 22990388Free PMC Article
Laforêt P, Ørngreen M, Preisler N, Andersen G, Vissing J
Arch Neurol 2012 Apr;69(4):530-3. doi: 10.1001/archneurol.2011.631. PMID: 22491199
Coassin S, Schweiger M, Kloss-Brandstätter A, Lamina C, Haun M, Erhart G, Paulweber B, Rahman Y, Olpin S, Wolinski H, Cornaciu I, Zechner R, Zimmermann R, Kronenberg F
PLoS Genet 2010 Dec 9;6(12):e1001239. doi: 10.1371/journal.pgen.1001239. PMID: 21170305Free PMC Article

Prognosis

Akman HO, Davidzon G, Tanji K, Macdermott EJ, Larsen L, Davidson MM, Haller RG, Szczepaniak LS, Lehman TJ, Hirano M, DiMauro S
Neuromuscul Disord 2010 Jun;20(6):397-402. Epub 2010 May 14 doi: 10.1016/j.nmd.2010.04.004. PMID: 20471263
Duncan RE, Wang Y, Ahmadian M, Lu J, Sarkadi-Nagy E, Sul HS
J Lipid Res 2010 Feb;51(2):309-17. Epub 2009 Aug 19 doi: 10.1194/jlr.M000729. PMID: 19692632Free PMC Article
Campagna F, Nanni L, Quagliarini F, Pennisi E, Michailidis C, Pierelli F, Bruno C, Casali C, DiMauro S, Arca M
Biochem Biophys Res Commun 2008 Dec 19;377(3):843-6. Epub 2008 Oct 24 doi: 10.1016/j.bbrc.2008.10.081. PMID: 18952067
Fischer J, Lefèvre C, Morava E, Mussini JM, Laforêt P, Negre-Salvayre A, Lathrop M, Salvayre R
Nat Genet 2007 Jan;39(1):28-30. Epub 2006 Dec 24 doi: 10.1038/ng1951. PMID: 17187067

Clinical prediction guides

Xu C, Zhao Y, Liu J, Zhang W, Wang Z, Yuan Y
Muscle Nerve 2015 Jun;51(6):922-7. Epub 2015 Apr 24 doi: 10.1002/mus.24507. PMID: 25363365
Laforêt P, Stojkovic T, Bassez G, Carlier PG, Clément K, Wahbi K, Petit FM, Eymard B, Carlier RY
Mol Genet Metab 2013 Feb;108(2):125-31. Epub 2012 Dec 28 doi: 10.1016/j.ymgme.2012.12.004. PMID: 23333026
Coassin S, Schweiger M, Kloss-Brandstätter A, Lamina C, Haun M, Erhart G, Paulweber B, Rahman Y, Olpin S, Wolinski H, Cornaciu I, Zechner R, Zimmermann R, Kronenberg F
PLoS Genet 2010 Dec 9;6(12):e1001239. doi: 10.1371/journal.pgen.1001239. PMID: 21170305Free PMC Article
Campagna F, Nanni L, Quagliarini F, Pennisi E, Michailidis C, Pierelli F, Bruno C, Casali C, DiMauro S, Arca M
Biochem Biophys Res Commun 2008 Dec 19;377(3):843-6. Epub 2008 Oct 24 doi: 10.1016/j.bbrc.2008.10.081. PMID: 18952067
Fischer J, Lefèvre C, Morava E, Mussini JM, Laforêt P, Negre-Salvayre A, Lathrop M, Salvayre R
Nat Genet 2007 Jan;39(1):28-30. Epub 2006 Dec 24 doi: 10.1038/ng1951. PMID: 17187067

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