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Lipodystrophy, congenital generalized, type 5(CGL5)

MedGen UID:
1847991
Concept ID:
C5882745
Disease or Syndrome
Synonym: CGL5
 
Gene (location): PCYT1A (3q29)
 
Monarch Initiative: MONDO:0958023
OMIM®: 620680

Definition

Congenital generalized lipodystrophy type 5 (CGL5) is an autosomal recessive metabolic disorder characterized by childhood onset of lipodystrophy, severe nonalcoholic fatty liver disease, dyslipidemia, hypertriglyceridemia, low HDL, and insulin-resistant diabetes mellitus. Affected individuals also have short stature (Payne et al., 2014). For a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594). [from OMIM]

Clinical features

From HPO
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).
Decreased body fat percentage
MedGen UID:
1723230
Concept ID:
C5421709
Finding
The percentage of fat as a part of total body weight below the norm, usually defined as less than 14% for females and less than 8% for males.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Loss of subcutaneous adipose tissue in limbs
MedGen UID:
325248
Concept ID:
C1837764
Finding
Loss (disappearance) of previously present subcutaneous fat tissue in arm or leg.
Type 2 diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
WFS1 spectrum disorder (WFS1-SD) comprises classic WFS1 spectrum disorder and nonclassic WFS1 spectrum disorder. Classic WFS1-SD, a progressive neurodegenerative disorder, is characterized by onset of diabetes mellitus and optic atrophy before age 16 years. Additional complications may include one or more of the following: variable hearing impairment / deafness, diabetes insipidus, neurologic abnormalities, neurogenic bladder, and psychiatric abnormalities. Nonclassic WFS1-SD is less common than classic WFS1-SD. Phenotypes that appear to be milder than classic WFS1-SD include: optic atrophy and hearing impairment; neonatal diabetes, profound congenital deafness, and cataracts; isolated diabetes mellitus; isolated congenital cataracts; and isolated congenital, slowly progressive, and low-frequency (<2000 Hz) sensorineural hearing loss.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Insulin resistance
MedGen UID:
43904
Concept ID:
C0021655
Pathologic Function
Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.
Decreased HDL cholesterol concentration
MedGen UID:
57731
Concept ID:
C0151691
Finding
An decreased concentration of high-density lipoprotein cholesterol in the blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
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.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Hyperinsulinemia
MedGen UID:
43779
Concept ID:
C0020459
Disease or Syndrome
An increased concentration of insulin in the blood.
Decreased adiponectin level
MedGen UID:
892903
Concept ID:
C4073127
Finding
A reduced circulating concentration of adiponectin, a 30-kDa complement C1-related protein that is the most abundant secreted protein expressed in adipose tissue.

Professional guidelines

PubMed

Araujo-Vilar D, Sánchez-Iglesias S, Guillín-Amarelle C, Castro A, Lage M, Pazos M, Rial JM, Blasco J, Guillén-Navarro E, Domingo-Jiménez R, del Campo MR, González-Méndez B, Casanueva FF
Endocrine 2015 May;49(1):139-47. Epub 2014 Nov 4 doi: 10.1007/s12020-014-0450-4. PMID: 25367549Free PMC Article

Recent clinical studies

Etiology

Yildirim Simsir I, Tuysuz B, Ozbek MN, Tanrikulu S, Celik Guler M, Karhan AN, Denkboy Ongen Y, Gunes N, Soyaltin UE, Altay C, Nur B, Ozalkak S, Akgun Dogan O, Dursun F, Pekkolay Z, Eren MA, Usta Y, Ozisik S, Ozgen Saydam B, Adiyaman SC, Unal MC, Gungor Semiz G, Turan I, Eren E, Kayserili H, Jeru I, Vigouroux C, Atik T, Onay H, Ozen S, Arioglu Oral E, Akinci B
Diabetes Obes Metab 2023 Jul;25(7):1950-1963. Epub 2023 Apr 11 doi: 10.1111/dom.15061. PMID: 36946378
Lima GEDCP, Fernandes VO, Montenegro APDR, Carvalho AB, Karbage LBAS, Aguiar LB, Macedo MSR, Ferreira LAA, Montenegro Júnior RM
Arch Endocrinol Metab 2019 Feb;63(1):79-83. doi: 10.20945/2359-3997000000096. PMID: 30864635Free PMC Article
Eiden M, Koulman A, Hatunic M, West JA, Murfitt S, Osei M, Adams C, Wang X, Chu Y, Marney L, Roberts LD, O'Rahilly S, Semple RK, Savage DB, Griffin JL
Genome Med 2015;7(1):63. Epub 2015 Jun 28 doi: 10.1186/s13073-015-0179-6. PMID: 26273324Free PMC Article
Araujo-Vilar D, Sánchez-Iglesias S, Guillín-Amarelle C, Castro A, Lage M, Pazos M, Rial JM, Blasco J, Guillén-Navarro E, Domingo-Jiménez R, del Campo MR, González-Méndez B, Casanueva FF
Endocrine 2015 May;49(1):139-47. Epub 2014 Nov 4 doi: 10.1007/s12020-014-0450-4. PMID: 25367549Free PMC Article
Nishiyama A, Yagi M, Awano H, Okizuka Y, Maeda T, Yoshida S, Takeshima Y, Matsuo M
Pediatr Int 2009 Dec;51(6):775-9. Epub 2009 Mar 31 doi: 10.1111/j.1442-200X.2009.02863.x. PMID: 19438831

Diagnosis

Rajan R, Chapla A, Johnson J, Varghese D, Asha HS, Jebasingh F, Kapoor N, Paul TV, Thomas N
Sci Rep 2024 Nov 16;14(1):28277. doi: 10.1038/s41598-024-79516-7. PMID: 39550450Free PMC Article
Yildirim Simsir I, Tuysuz B, Ozbek MN, Tanrikulu S, Celik Guler M, Karhan AN, Denkboy Ongen Y, Gunes N, Soyaltin UE, Altay C, Nur B, Ozalkak S, Akgun Dogan O, Dursun F, Pekkolay Z, Eren MA, Usta Y, Ozisik S, Ozgen Saydam B, Adiyaman SC, Unal MC, Gungor Semiz G, Turan I, Eren E, Kayserili H, Jeru I, Vigouroux C, Atik T, Onay H, Ozen S, Arioglu Oral E, Akinci B
Diabetes Obes Metab 2023 Jul;25(7):1950-1963. Epub 2023 Apr 11 doi: 10.1111/dom.15061. PMID: 36946378
Costa S, Sampaio L, Berta Sousa A, Xing C, Agarwal AK, Garg A
J Clin Endocrinol Metab 2022 Aug 18;107(9):2433-2438. doi: 10.1210/clinem/dgac406. PMID: 35857714Free PMC Article
Craveiro Sarmento AS, Ferreira LC, Lima JG, de Azevedo Medeiros LB, Barbosa Cunha PT, Agnez-Lima LF, Galvão Ururahy MA, de Melo Campos JTA
Mutat Res Rev Mutat Res 2019 Jul-Sep;781:30-52. Epub 2019 Mar 23 doi: 10.1016/j.mrrev.2019.03.005. PMID: 31416577
Ponte CMM, Fernandes VO, Gurgel MHC, Vasconcelos ITGF, Karbage LBAS, Liberato CBR, Negrato CA, Gomes MB, Montenegro APDR, Montenegro Júnior RM
BMC Cardiovasc Disord 2018 Jan 12;18(1):6. doi: 10.1186/s12872-017-0738-4. PMID: 29329523Free PMC Article

Therapy

Brener A, Zeitlin L, Wilnai Y, Birk OS, Rosenfeld T, Chorna E, Lebenthal Y
Acta Diabetol 2022 May;59(5):711-719. Epub 2022 Feb 8 doi: 10.1007/s00592-022-01854-7. PMID: 35137278
Fukaishi T, Minami I, Masuda S, Miyachi Y, Tsujimoto K, Izumiyama H, Hashimoto K, Yoshida M, Takahashi S, Kashimada K, Morio T, Kosaki K, Maezawa Y, Yokote K, Yoshimoto T, Yamada T
Endocr J 2020 Feb 28;67(2):211-218. Epub 2019 Nov 8 doi: 10.1507/endocrj.EJ19-0226. PMID: 31708526
Çelo E, Kalari B, Toti F
Georgian Med News 2018 Apr;(277):27-31. PMID: 29745909
Araujo-Vilar D, Sánchez-Iglesias S, Guillín-Amarelle C, Castro A, Lage M, Pazos M, Rial JM, Blasco J, Guillén-Navarro E, Domingo-Jiménez R, del Campo MR, González-Méndez B, Casanueva FF
Endocrine 2015 May;49(1):139-47. Epub 2014 Nov 4 doi: 10.1007/s12020-014-0450-4. PMID: 25367549Free PMC Article
Park JY, Chong AY, Cochran EK, Kleiner DE, Haller MJ, Schatz DA, Gorden P
J Clin Endocrinol Metab 2008 Jan;93(1):26-31. Epub 2007 Oct 16 doi: 10.1210/jc.2007-1856. PMID: 17940115Free PMC Article

Prognosis

Brener A, Zeitlin L, Wilnai Y, Birk OS, Rosenfeld T, Chorna E, Lebenthal Y
Acta Diabetol 2022 May;59(5):711-719. Epub 2022 Feb 8 doi: 10.1007/s00592-022-01854-7. PMID: 35137278
Araujo-Vilar D, Sánchez-Iglesias S, Guillín-Amarelle C, Castro A, Lage M, Pazos M, Rial JM, Blasco J, Guillén-Navarro E, Domingo-Jiménez R, del Campo MR, González-Méndez B, Casanueva FF
Endocrine 2015 May;49(1):139-47. Epub 2014 Nov 4 doi: 10.1007/s12020-014-0450-4. PMID: 25367549Free PMC Article
Nishiyama A, Yagi M, Awano H, Okizuka Y, Maeda T, Yoshida S, Takeshima Y, Matsuo M
Pediatr Int 2009 Dec;51(6):775-9. Epub 2009 Mar 31 doi: 10.1111/j.1442-200X.2009.02863.x. PMID: 19438831
Park JY, Chong AY, Cochran EK, Kleiner DE, Haller MJ, Schatz DA, Gorden P
J Clin Endocrinol Metab 2008 Jan;93(1):26-31. Epub 2007 Oct 16 doi: 10.1210/jc.2007-1856. PMID: 17940115Free PMC Article
Jin J, Cao L, Zhao Z, Shen S, Kiess W, Zhi D, Ye R, Cheng R, Chen L, Yang Y, Luo F
Eur J Endocrinol 2007 Dec;157(6):783-7. doi: 10.1530/EJE-07-0393. PMID: 18057387

Clinical prediction guides

Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ
J Clin Endocrinol Metab 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491. PMID: 37595266Free PMC Article
Lima GEDCP, Fernandes VO, Montenegro APDR, Carvalho AB, Karbage LBAS, Aguiar LB, Macedo MSR, Ferreira LAA, Montenegro Júnior RM
Arch Endocrinol Metab 2019 Feb;63(1):79-83. doi: 10.20945/2359-3997000000096. PMID: 30864635Free PMC Article
Ponte CMM, Fernandes VO, Gurgel MHC, Vasconcelos ITGF, Karbage LBAS, Liberato CBR, Negrato CA, Gomes MB, Montenegro APDR, Montenegro Júnior RM
BMC Cardiovasc Disord 2018 Jan 12;18(1):6. doi: 10.1186/s12872-017-0738-4. PMID: 29329523Free PMC Article
Lima JG, Nobrega LHC, Lima NN, Dos Santos MCF, Baracho MFP, Bandeira F, Capistrano L, Freire Neto FP, Jeronimo SMB
J Clin Densitom 2018 Jan-Mar;21(1):61-67. Epub 2016 Nov 25 doi: 10.1016/j.jocd.2016.10.002. PMID: 27894728
Faria CA, Moraes RS, Sobral-Filho DC, Rego AG, Baracho MF, Egito ES, Brandão-Neto J
Europace 2009 Jun;11(6):763-9. Epub 2009 Apr 17 doi: 10.1093/europace/eup095. PMID: 19376819

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