Year: 2024
Type: article
Study design: Case Report
Abstract: Congenital generalized lipodystrophy is a rare metabolic disease with autosomal recessive inheritance. It is characterized by a reduction of subcutaneous adipose tissue, ectopic lipid deposition, and the development of a number of metabolic disorders including insulin resistance diabetes mellitus, fatty liver degeneration and hepatitis, and arterial hypertension. One of clinical manifestation of the disease is kidney damage often leading to proteinuria of varying severity. However, the pathophysiological mechanisms underlying kidney damage in this condition are not yet fully understood. The aim of the study was to perform a clinical and morphological analysis of renal complications in a 32-year-old woman with Berardinelli-Seip syndrome and a rare heterozygous mutation in the AGPAT2 gene, a nucleotide substitution C.636C>T (L212L). This case report incorporated data from patient’s the medical history, intravital laboratory and instrumental studies, and both qualitative and quantitative morphological analysis of a nephrobiopsy sample. Clinical signs and morphological finding at light-optical and electron microscopic levels are presented, highlighting the reorganization of glomeruli tissue elements. The main clinical manifestations of kidney damage in this patient included arterial hypertension, progressive facial edema, swelling of the lower extremities and lumbar region, advanced nephrotic syndrome, and impaired nitrogen-excretory kidney function. Morphological examination did not reveal histological or ultrastructural signs of diabetic microangiopathy or nephropathy. Instead, findings included large glomeruli with a lobular configuration of the glomerular tuft, moderate mesangial expansion, segmental thickening of the capillary loop, and duplication of the glomerular basal membrane. There was deposition of immune complexes, primarily of the C3c complement fragment, along the capillary wall and in the paramesangial and mesangial regions, forming hyperdense osmiophilic ribbon-like and garland structures. These findings led to the classification of renal damage as C3 glomerulopathy. The study suggests that various mutations in the AGPAT2 gene may influence renal complications in Berardinelli-Seip syndrome, potentially contributing to a broader clinical spectrum, including the possibility of developing C3 glomerulopathy.
Source: Nephrology and Dialysis
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4406270413