Lipodystrophy is a congenital or acquired disorder characterized by either complete or partial lack of adipose tissue. In some of these disorders, there is also the apparent accumulation of fat in other regions of the body. The primary defect is the loss of functional adipocytes, leading to ectopic steatosis, insulin resistance and severe dyslipidemia. The main cause of insulin resistance is the fact that the excess energy cannot be stored in adipose tissue, which is secondary to either the near total lack of adipocyte expandability in patients with generalized lipodystrophy, or a limited capacity to expand in partial lipodystrophy.
Abnormal appearance due to the absence or abnormal distribution of subcutaneous fat is noted within the first two years of life. During childhood, these patients manifest a high appetite, accelerated linear growth and advanced bone age. The onset of protuberant abdomen due to hepatomegaly caused by fatty infiltration of the liver is also common, which leads to severe cirrhosis. The mode of inheritance is autosomal recessive.
The Igenomix Lipodystrophy Precision Panel can be used to make an accurate and directed diagnosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
- The Igenomix Lipodystrophy Precision Panel is indicated for those patients with a clinical diagnosis or suspicion presenting with or without the following manifestations:
- Loss of fat from upper extremities
- Accumulation of fat into lower bodies
- High appetite
- Velvety dark skin
- Disproportionate size of hands and feet
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of multidisciplinary treatment including pharmacological treatment with thiazolidinediones/PPARG modulators to increase adiponectin levels, and metformin in combination with insulin to stabilize glucose levels in blood. A proper low-fat diet may help reduce the symptoms, although it will not reverse lipoatrophy.
- Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
Rinaldo, P., Matern, D., & Bennett, M. (2002). Fatty Acid Oxidation Disorders. Annual Review Of Physiology, 64(1), 477-502. doi: 10.1146/annurev.physiol.64.082201.154705
Knottnerus, S., Bleeker, J. C., Wüst, R., Ferdinandusse, S., IJlst, L., Wijburg, F. A., Wanders, R., Visser, G., & Houtkooper, R. H. (2018). Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Reviews in endocrine & metabolic disorders, 19(1), 93–106. https://doi.org/10.1007/s11154-018-9448-1
Wanders, R., Vaz, F. M., Waterham, H. R., & Ferdinandusse, S. (2020). Fatty Acid Oxidation in Peroxisomes: Enzymology, Metabolic Crosstalk with Other Organelles and Peroxisomal Disorders. Advances in experimental medicine and biology, 1299, 55–70. https://doi.org/10.1007/978-3-030-60204-8_5
Rinaldo, P., Matern, D., & Bennett, M. J. (2002). Fatty acid oxidation disorders. Annual review of physiology, 64, 477–502. https://doi.org/10.1146/annurev.physiol.64.082201.154705
Roe, C., & Mochel, F. (2006). Anaplerotic diet therapy in inherited metabolic disease: Therapeutic potential. Journal Of Inherited Metabolic Disease, 29(2-3), 332-340. doi: 10.1007/s10545-006-0290-3
Olpin S. E. (2013). Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability. Journal of inherited metabolic disease, 36(4), 645–658. https://doi.org/10.1007/s10545-013-9611-5