Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy.

BACKGROUND: Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. CASE-DIAGNOSIS/TREATMENT: A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab. CONCLUSIONS: Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD.

[Partial lipodystrophy with C3 complement deficiency in 8 years old girl]. / Zespól lipodystrofii ograniczonej - czesciowej, z niedoborem skladowej c3 dopelniacza u 8-letniej dziewczynki.

Lipodystrophy is a rare, heterogenic disorder, leading to the loss of adipose tissue. Several main types of the disease are distinguished according to age of onset and localization of fat atrophy. The authors present the case of 8 years old girl with partial lipodystrophy, C3 complement deficiency and autoimmunologic disorder.

Partial lipodystrophy and renal disease.

Partial lipodystrophy is a rare disorder with both autosomal recessive and familial forms. The cutaneous findings, which are often subtle, consist of a gradual loss of subcutaneous fat from the face and upper body. Low levels of C3, occasionally low C5 and the presence of the nephritic factor help to identify these patients. Associated systemic abnormalities include the development of mesangiocapillary glomerulonephritis and an increased incidence of autoimmune diseases. Recognition of this unusual disorder is essential for diagnosis and treatment of underlying potentially life- threatening disease.

Screening for complement deficiencies in patients surviving from epidemic meningococcal disease.

Sera from 132 patients surviving from meningococcal disease during the high-endemic period 1 January 1980 to 31 December 1984 on the Faroe Islands were screened for deficiencies of the complement (C) system by measuring hemolytic complement function in serum. Samples from 12 patients with reduced C function were further investigated by immunochemical quantification of individual C proteins. One patients was identified with C3-deficiency (C3-concentration 6% of normal) due to the presence of C3 nephritic factor (C3NeF) in serum. In addition, eight patients had minor aberrations in one or several complement proteins. It is concluded, that C deficiency is not an important risk factor during epidemics of meningococcal disease. The C3NeF activity could not be absorbed with Neisseria meningitidis group B, type 15, indicating absence of crossreactivity between neisserial antigens and C3NeF.

An inherited defect in the C3 convertase, C3b,Bb, associated with glomerulonephritis.

The control of the amplification C3 convertase, C3b,Bb, of the serum complement system has been found to be defective in five members of a family spanning three generations. One of the five has membranoproliferative glomerulonephritis (MPGN) type III and another has mild idiopathic rapidly progressive glomerulonephritis. The defect is manifested by low serum concentrations of C3 and usually factor B with normal levels of the proteins which control the convertase, H and I. C3 nephritic factor (C3NeF) was not demonstrable. Enhanced C3 conversion was produced by the incubation of their serum at 37 degrees C for 30 min. This conversion was further accelerated by incubation after increasing the serum magnesium concentration by increments ranging from 0.25 to 1.9 mM. Incremental additions of H to serum depleted of H indicated that the amplification convertase of affected family members required more H for its inhibition than did that of normal subjects. This requirement was reduced by the addition of purified normal C3 but not by the addition of purified C3 of the propositus. It is postulated that affected family members are heterozygous for a gene producing an abnormal C3 which, as a constituent of the amplification convertase, C3b,Bb, confers resistance to H. Investigation of this apparently nephritogenic defect may provide insight into the pathogenesis of these glomerulonephritides.