Novel Missense LCAT Gene Mutation Associated with an Atypical Phenotype of Familial LCAT Deficiency in Two Portuguese Brothers.

Familial lecithin-cholesterol acyltransferase deficiency (FLD) is a rare recessive disorder of cholesterol metabolism, caused by loss-of-function mutations in the human LCAT gene, leading to alterations in the lipid/lipoprotein profile, with extremely low HDL levels.The classical FLD phenotype is characterized by diffuse corneal opacification, haemolytic anaemia and proteinuric chronic kidney disease (CKD); an incomplete form, only affecting the corneas, has been reported in a few families worldwide.We describe an intermediate phenotype of LCAT deficiency, with CKD preceding the development of corneal clouding, in two Portuguese brothers apparently homozygous for a novel missense LCAT gene mutation. The atypical phenotype, the diagnosis of membranous nephropathy in the proband's native kidney biopsy, the late-onset and delayed recognition of the corneal opacification, the co-segregation with Gilbert syndrome and the late recurrence of the primary disease in kidney allograft all contributed to obscure the diagnosis of an LCAT deficiency syndrome for many years.A major teaching point is that on standard light microscopy examination the kidney biopsies of patients with LCAT deficiency with residual enzyme activity may not show significant vacuolization and may be misdiagnosed as membranous nephropathy. The cases of these two patients also illustrate the importance of performing detailed physical examination in young adults presenting with proteinuric CKD, as the most important clue to the diagnosis of FLD is in the eyes.

Early-onset of disseminated cryptococcal infection in two renal transplant recipients.

Cryptococcosis is the third most common invasive fungal infection in organ transplant recipients after candidiasis and aspergillosis. Newly acquired and reactivation of latent infection are the major causes of infection, with typical later-onset and mainly as disseminated infection. The type and intensity of immunosuppression, diabetes mellitus and other co-morbidities as well as uremia seem to be important determinants on clinical presentation and outcome. Moreover, the diagnosis is not always apparent since it usually presents subacutely, as well as mimicking bacterial infections, which may be responsible for a delay in the diagnosis. Thus, a high degree of suspicion and need of invasive procedures for microbiological and histological evaluation are critical for definitive diagnosis and prompt institution of adequate treatment. We report two cases of disseminated cryptococcosis with different presentations and with an early-onset after renal transplantation.

Rituximab for steroid-dependent nephrotic syndrome.

Minimal change disease (MCD) is characterized by marked sensitivity to glucocorticoid therapy. However, in 40 - 50% of all cases the disease presents with frequent relapses and needs repeated courses of steroids as well as additional immunosuppressive therapy including azathioprine, cyclophosphamide or cyclosporine. Because such regimens are associated with significant toxicity, the therapeutic challenge of this disease is to identify the treatment with the highest probability of producing a sustained remission with the lowest risk of toxicity. There is increasing evidence that rituximab may play an important role in the treatment of idiopathic nephrotic syndrome. Here, we present an adult patient with steroid-sensitive but high-dose steroid-dependent MCD beginning in childhood with a heavy history of multiple immunosuppressive therapy that was brought into 1 year sustained remission of proteinuria with two infusions of rituximab (375 mg/m2).