Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective loss of body fat is the hallmark of patients with lipodystrophies. Among genetic lipodystrophies, fat loss is observed either from birth, as in congenital generalized lipodystrophy, or later in life, as in familial partial lipodystrophy. The extent of fat loss also varies among subtypes of lipodystrophies. Patients develop hyperinsulinemia, acanthosis nigricans, hypertriglyceridemia, diabetes mellitus, and hepatic steatosis. Defects in several genes, such as those encoding an enzyme (AGPAT2), a nuclear receptor (PPARgamma), a nuclear lamina protein (LMNA) and its processing endoprotease (ZMPSTE24), a kinase (AKT2), and a protein of unknown function (BSCL2), have been found in patients with genetic lipodystrophies. Additional loci remain to be discovered. We discuss features of autosomal recessive and dominant types of lipodystrophies and therapeutic interventions available for these patients.
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PMID:Genetic basis of lipodystrophies and management of metabolic complications. 1640 51

Lack of adipose tissue, either complete or partial, is the hallmark of disorders known as lipodystrophies. Patients with lipodystrophies suffer from metabolic complications similar to those associated with obesity, including insulin resistance, type 2 diabetes, hypertriglyceridemia, and hepatic steatosis. The loss of body fat in inherited lipodystrophies can be caused by defects in the development and/or differentiation of adipose tissue as a consequence of mutations in a number of genes, including PPARG (encoding a nuclear hormone receptor), AGPAT2 (encoding an enzyme involved in the biosynthesis of triglyceride and phospholipids), AKT2 (encoding a protein involved in insulin signal transduction), and BSCL2 (encoding seipin, whose role in the adipocyte biology remains unclear). The loss of body fat can also be caused by the premature death of adipocytes due to mutations in lamin A/C, nuclear lamina proteins, and ZMPSTE24, which modifies the prelamin A post-translationally. In this review, we focus on the molecular basis of inherited lipodystrophies as they relate to adipocyte biology and their associated phenotypic manifestations.
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PMID:Genetic disorders of adipose tissue development, differentiation, and death. 1672 6

We report on a 25-year-old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome (MFS; fulfilling the Ghent criteria) with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia in addition to the severe generalized lipodystrophy. She lacked insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. Mutation analysis in the gene encoding fibrillin 1 (FBN1) revealed a novel de novo heterozygous deletion, c.8155_8156del2 in exon 64. The severe generalized lipodystrophy in this patient with progeroid features has not previously been described in other patients with MFS and FBN1 mutations. We did not find a mutation in genes known to be associated with congenital lipodystrophy (APGAT2, BSCL2, CAV1, PTRF-CAVIN, PPARG, LMNB2) or with Hutchinson-Gilford progeria (ZMPSTE24, LMNA/C). Other progeria syndromes were considered unlikely because premature greying, hypogonadism, and scleroderma-like skin disease were not present. Our patient shows striking similarity to two patients who have been published in this journal by O'Neill et al. [O'Neill et al. (2007); Am J Med Genet Part A 143A:1421-1430] with the diagnosis of neonatal progeroid syndrome (NPS). This condition also known as Wiedemann-Rautenstrauch syndrome is a rare disorder characterized by accelerated aging and lipodystrophy from birth, poor postnatal weight gain, and characteristic facial features. The course is usually progressive with early lethality. However this entity seems heterogeneous. We suggest that our patient and the two similar cases described before represent a new entity, a subgroup of MFS with overlapping features to NPS syndrome.
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PMID:Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3' terminus of the FBN1-gene. 2097 88