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

Autor:	Castro-Ferreira I; Service of Nephrology, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal. inescastroferreira@sapo.pt.; I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Oporto, Portugal. inescastroferreira@sapo.pt., Carmo R; Service of Nephrology, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal., Silva SE; Service of Ophthalmology, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal.; Department of Organs of the Senses, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal., Corrêa O; Labco Clinical Laboratory Dr. Joāo Ribeiro, Rua Augusto Simões, 1430 - 1°, salas 1-3, 4470-147, Maia, Portugal., Fernandes S; I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Oporto, Portugal.; Unit of Genetics, Department of Pathology, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal., Sampaio S; Service of Nephrology, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal.; I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Oporto, Portugal., Pedro RP; Service of Pathology, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal.; Department of Pathology, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal., Praça A; Service of Nephrology, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal.; NephroCare Haemodialysis Clinic, Rua João Mendes Cardoso, 24-C, 4520-233, Santa Maria da Feira, Portugal., Oliveira JP; I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Oporto, Portugal.; NephroCare Haemodialysis Clinic, Rua João Mendes Cardoso, 24-C, 4520-233, Santa Maria da Feira, Portugal.; Service of Medical Genetics and Reference Centre for Inherited Metabolic Diseases, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal.
Jazyk:	angličtina
Zdroj:	JIMD reports [JIMD Rep] 2018; Vol. 40, pp. 55-62. Date of Electronic Publication: 2017 Oct 06.
DOI:	10.1007/8904_2017_57
Abstrakt:	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.
Databáze:	MEDLINE
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