Laboratory Studies
Urinalysis may be helpful in progressive lipodystrophy. Approximately one third of patients with this condition have some degree of glomerulonephritis, and, if hypocomplementemia is present, the risk is higher. Manifestations of glomerulonephritis range from asymptomatic proteinuria to a nephrotic syndrome and renal insufficiency.
Baseline creatinine and blood urea nitrogen studies, as well as urine studies, should be performed to detect proteinuria and hematuria.
A CBC count should be obtained. Normochromic normocytic anemia is often present.
Immune studies can be ordered. Immune studies may be needed to identify patients with associated immune disorders, particularly if the diagnosis of partial lipodystrophy is made at a younger age. The presence of serum antinuclear antibodies and anti–double-stranded DNA antibodies has been reported in some patients.
Complement levels may be determined. The most common laboratory abnormality in patients with progressive lipodystrophy is a low complement level. Hypocomplementemia is characterized by a low C3 complement level, a normal C4 level, and the presence of C3 nephritic factor.
Lipid studies may be performed. Hypertriglyceridemia secondary to nephrotic syndrome may be present in some patients.
Genetic testing may identify patients whose phenotypes may be inapparent, but who may still be affected by severe metabolic complications. [22]
Imaging Studies
Head MRIs show evidence of fat loss in progressive lipodystrophy patients.
Other Tests
Immunofluorescence studies in progressive lipodystrophy patients show deposits of C3 in a granular pattern in the basement membranes.
Procedures
Skin biopsy findings confirm the progressive lipodystrophy diagnosis. Kidney biopsy is required if a glomerulonephritis is associated with the progressive lipodystrophy.
Histologic Findings
Cutaneous biopsy in progressive lipodystrophy reveals a reduction or absence of subcutaneous fat in affected areas. Subcutaneous fat cells are decreased in number.
Traces of adipose tissue may be found around hair follicles and sebaceous glands. The dermis and epidermis are normal.
Renal biopsy findings are characterized by a membranoproliferative glomerulonephritis with a proliferation of mesangial cells and matrix, as well as thickening of the basement membranes by amorphous electron-dense deposits.
Immunofluorescence studies show deposits of C3 in a granular pattern in the basement membranes.
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Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B to its active enzymatic form. Factor D is expressed to a higher extent in the fat cells of the upper half of the body compared with the lower half, and it is possibly this regional difference that accounts for the restriction of fat loss to the head, arms, and trunk. C3Nef is also associated with type II, dense-deposit membranoproliferative glomerulonephritis in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway.
