Details of Disease

General Information of Disease (ID: DIS4XF8N)

• Disease Name: Congenital generalized lipodystrophy
• Synonyms: congenital generalised lipodystrophy (disease); lipodystrophy, congenital generalised; hereditary generalized lipodystrophy; lipodystrophy, congenital generalized; congenital generalized lipodystrophy (disease); familial generalised lipodystrophy; congenital generalized lipodystrophy; hereditary generalised lipodystrophy; familial generalized lipodystrophy
• Definition: An extremely rare autosomal recessive condition, characterized by an extreme scarcity of fat in the subcutaneous tissues.
• Disease Hierarchy:
  DISC6HI8: Generalized lipodystrophy
  DIS1BE1A: Hereditary lipodystrophy
  DIS4XF8N: Congenital generalized lipodystrophy
• Disease Identifiers:
  MONDO ID: MONDO_0006536
  MESH ID: D052497
  UMLS CUI: C0221032
  MedGen ID: 67438
  HPO ID: HP:0009059
  SNOMED CT ID: 284449005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Metreleptin	DM1NOEK	Approved	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CAV1	TTXUBN2	Limited	Genetic Variation	[2]
GART	TTEXB9Z	Limited	Genetic Variation	[3]
PDE3B	TTN34SQ	Limited	Genetic Variation	[4]
PLIN1	TTIV27N	Limited	Biomarker	[5]
AGPAT1	TTPL1TK	Strong	Altered Expression	[6]
AGPAT2	TT9AYVR	Strong	Biomarker	[7]
ANGPTL3	TT59GO7	Strong	Biomarker	[8]
FOS	TTOM5AU	Strong	GermlineCausalMutation	[9]
LEP	TTBJEZ5	Strong	Biomarker	[10]
PPARG	TTT2SVW	Strong	Genetic Variation	[11]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC2A2	DTUJPOL	Limited	Genetic Variation	[12]

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GARS1	OT5B6R9Y	Limited	Genetic Variation	[3]
LMNA	OT3SG7ZR	Limited	Genetic Variation	[10]
LPIN1	OTQ75KF2	Limited	Genetic Variation	[13]
LPIN2	OTRRTMXX	Limited	Genetic Variation	[13]
SETX	OTG3JNOQ	Limited	Biomarker	[14]
AGL	OTWBM7WY	moderate	Genetic Variation	[15]
CAVIN1	OTFO915U	Strong	Biomarker	[16]
GZMH	OTG3259L	Strong	Genetic Variation	[17]
SNAP23	OTY2MYBX	Definitive	Biomarker	[18]

References

• [1] Lipodystrophy Syndromes. Endocrinol Metab Clin North Am. 2016 Dec;45(4):783-797.
• [2] Characterization of a caveolin-1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy.Traffic. 2016 Dec;17(12):1297-1312. doi: 10.1111/tra.12452. Epub 2016 Nov 2.
• [3] Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome.J Neurol Sci. 2007 Dec 15;263(1-2):100-6. doi: 10.1016/j.jns.2007.06.047. Epub 2007 Jul 30.
• [4] Analysis of the insulin-sensitive phosphodiesterase 3B gene in type 2 diabetes.Diabetes Res Clin Pract. 2001 Nov;54(2):79-88. doi: 10.1016/s0168-8227(01)00287-x.
• [5] Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy.Front Immunol. 2018 Sep 19;9:2142. doi: 10.3389/fimmu.2018.02142. eCollection 2018.
• [6] Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.Endocrinology. 2017 Nov 1;158(11):3954-3973. doi: 10.1210/en.2017-00511.
• [7] Further delineation of AGPAT2 and BSCL2 related congenital generalized lipodystrophy in young infants.Eur J Med Genet. 2019 Sep;62(9):103542. doi: 10.1016/j.ejmg.2018.09.009. Epub 2018 Sep 25.
• [8] Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with generalized lipodystrophy.J Clin Lipidol. 2017 Mar-Apr;11(2):543-550. doi: 10.1016/j.jacl.2017.02.002. Epub 2017 Feb 24.
• [9] A mutation in the c-fos gene associated with congenital generalized lipodystrophy. Orphanet J Rare Dis. 2013 Aug 7;8:119. doi: 10.1186/1750-1172-8-119.
• [10] A case of generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement with short and long-term monitoring of the metabolic and endocrine profiles.Endocr J. 2020 Feb 28;67(2):211-218. doi: 10.1507/endocrj.EJ19-0226. Epub 2019 Nov 8.
• [11] Biallelic mutations at PPARG cause a congenital, generalized lipodystrophy similar to the Berardinelli-Seip syndrome. Eur J Med Genet. 2014 Sep;57(9):524-6. doi: 10.1016/j.ejmg.2014.06.006. Epub 2014 Jun 28.
• [12] Clinical and molecular characterization of neonatal diabetes and monogenic syndromic diabetes in Asian Indian children.Clin Genet. 2013 May;83(5):439-45. doi: 10.1111/j.1399-0004.2012.01939.x. Epub 2012 Aug 20.
• [13] Inborn errors of cytoplasmic triglyceride metabolism.J Inherit Metab Dis. 2015 Jan;38(1):85-98. doi: 10.1007/s10545-014-9767-7. Epub 2014 Oct 10.
• [14] Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study.Brain. 2008 May;131(Pt 5):1217-27. doi: 10.1093/brain/awn029. Epub 2008 Mar 5.
• [15] Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies.J Hum Genet. 2014 Jan;59(1):16-23. doi: 10.1038/jhg.2013.107. Epub 2013 Oct 24.
• [16] Postmortem Findings in a Young Man With Congenital Generalized Lipodystrophy, Type 4 Due to CAVIN1 Mutations.J Clin Endocrinol Metab. 2019 Mar 1;104(3):957-960. doi: 10.1210/jc.2018-01331.
• [17] Seipin deletion in mice enhances phosphorylation and aggregation of tau protein through reduced neuronal PPAR and insulin resistance.Neurobiol Dis. 2019 Jul;127:350-361. doi: 10.1016/j.nbd.2019.03.023. Epub 2019 Mar 22.
• [18] SNAP23 regulates BAX-dependent adipocyte programmed cell death independently of canonical macroautophagy.J Clin Invest. 2018 Aug 31;128(9):3941-3956. doi: 10.1172/JCI99217. Epub 2018 Aug 13.