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)

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total absence of body fat since birth with predisposition to insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis. Three CGL loci, AGPAT2, BSCL2, and CAV1, have been identified previously. Recently, mutations in polymerase I and transcript release factor (PTRF) were reported in five Japanese patients presenting with myopathy and CGL (CGL4). We report novel PTRF mutations and detailed phenotypes of two male and three female patients with CGL4 belonging to two pedigrees of Mexican origin (CGL7100 and CGL178) and one pedigree of Turkish origin (CGL180). All patients had near total loss of body fat and congenital myopathy manifesting as weakness, percussion-induced muscle mounding, and high serum creatine kinase levels. Four of them had hypertriglyceridemia. Three of them had atlantoaxial instability. Two patients belonging to CGL178 pedigree required surgery for pyloric stenosis in the first month of life. None of them had prolonged QT interval on electrocardiography but both siblings belonging to CGL7100 had exercise-induced ventricular arrhythmias. Three of them had mild acanthosis nigricans but had normal glucose tolerance. Two of them had hepatic steatosis. All patients had novel null mutations in PTRF gene. In conclusion, mutations in PTRF result in a novel phenotype that includes generalized lipodystrophy with mild metabolic derangements, myopathy, cardiac arrhythmias, atlantoaxial instability, and pyloric stenosis. It is unclear how mutations in PTRF, which plays an essential role in formation of caveolae, affect a wide variety of tissues resulting in a variable phenotype.
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PMID:Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. 2068 3

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

Congenital generalized lipodystrophy (CGL) is a heterogeneous autosomal recessive disorder characterized by a near complete lack of adipose tissue from birth and, later in life, the development of metabolic complications, such as diabetes mellitus, hypertriglyceridaemia and hepatic steatosis. Four distinct subtypes of CGL exist: type 1 is associated with AGPAT2 mutations; type 2 is associated with BSCL2 mutations; type 3 is associated with CAV1 mutations; and type 4 is associated with PTRF mutations. The products of these genes have crucial roles in phospholipid and triglyceride synthesis, as well as in the formation of lipid droplets and caveolae within adipocytes. The predominant cause of metabolic complications in CGL is excess triglyceride accumulation in the liver and skeletal muscle owing to the inability to store triglycerides in adipose tissue. Profound hypoleptinaemia further exacerbates metabolic derangements by inducing a voracious appetite. Patients require psychological support, a low-fat diet, increased physical activity and cosmetic surgery. Aside from conventional therapy for hyperlipidaemia and diabetes mellitus, metreleptin replacement therapy can dramatically improve metabolic complications in patients with CGL. In this Review, we discuss the molecular genetic basis of CGL, the pathogenesis of the disease's metabolic complications and therapeutic options for patients with CGL.
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PMID:Congenital generalized lipodystrophies--new insights into metabolic dysfunction. 2623 9