Background: Congenital generalized lipodystrophy (CGL) is characterized by the absence of most adipose tissue at birth due to an adipocyte differentiation block. For several forms of CGL, the underlying mutation and pathophysiological pathway has been identified. However, for many cases the genetic cause is still unknown.
Objective and hypotheses: We report a patient with CGL who showed a complete absence of fat apart from protective fat pads in a postnatal MRI. Adipocyte precursor cells prepared from his subepidermal tissue differentiated into adipocytes in the presence of a peroxisome proliferator-activated receptor (PPAR) y agonist. Further symptoms of the patient included a short stature, mental retardation, progressive contractions of his joints, muscular weakness, pronounced scoliosis, obstructive cardiomyopathy, multiple naevi, eruptive xanthoma, umbilical hernia, singular palmar grease and a triangular face with low sitting ears. Blood analysis showed a mild hypertriglyceridemia and a microcytic anemia. At the age of 8 years, the patient developed a pilocystic astrocytoma grade I° which was surgically removed. Within the next 2 years, two relapses occurred during which the tumor progressed to an anaplastic astrocytoma. Despite the normally severe diagnosis, after a radio-chemotherapy no relapse occurred in the last 3 years. It seems unlikely that the patient developed two rare diseases unconnected to each other.
Method: We screened for mutations known to cause CGL (BSCL 2, AGPAT, Caveolin 1, PTRV Cavin) and performed an array CGH.
Results: No pathological changes could be found.
Conclusion: Though we did not find a mutation, a hypothetical mutual cause might lie in the PPARy pathway, since PPARy is essential for adipocyte differentiation and its expression is increased in human glioma tissue. However so far, a mutation in this pathway has not been described either for anaplastic astrocytoma or for generalized lipodystrophy (in contrast to partial lipodystrophy).
20 - 22 Sep 2014
European Society for Paediatric Endocrinology