Abstract: SA-PO599
Comprehensive Analysis of the Renal and Systemic Phenotypes Associated with Familial Deficiency of Lecithin-Cholesterol Acyltransferase: a Case Series
Session Information
- Noncystic Mendelian Diseases
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Genetic Diseases of the Kidney
- 802 Non-Cystic Mendelian Diseases
Authors
- Sampaio, Carlos T., University of Sao Paulo, Sao Paulo, Brazil
- Balbo, Bruno E., University of Sao Paulo, Sao Paulo, Brazil
- Saraiva, Leonardo C., University of Sao Paulo, Sao Paulo, Brazil
- Nakano, Henrique R., University of Sao Paulo, Sao Paulo, Brazil
- Amaral, Andressa G., University of Sao Paulo, Sao Paulo, Brazil
- Costa, Eliene, University of Sao Paulo, Sao Paulo, Brazil
- Watanabe, Elieser H., University of Sao Paulo, Sao Paulo, Brazil
- Neves, Precil D, University of Sao Paulo, Sao Paulo, Brazil
- Chacra, Ana P., University of Sao Paulo, Sao Paulo, Brazil
- Maranhao, Raul, University of Sao Paulo, Sao Paulo, Brazil
- Guerra, Antonio A., University of Sao Paulo, Sao Paulo, Brazil
- Braga, Ricardo M., University of Sao Paulo, Sao Paulo, Brazil
- Santo, Ruth M., University of Sao Paulo, Sao Paulo, Brazil
- Testagrossa, Leonardo A., University of Sao Paulo, Sao Paulo, Brazil
- Reis, Marlene A., Federal University of Triangulo Mineiro, Uberaba, Brazil
- Silva, Junior A., Piaui Municipal Service, Sao Francisco, Brazil
- Carrascossi, Henrique, Araraquara Municipal Service, Araraquara, Brazil
- Onuchic, Luiz F., University of Sao Paulo, Sao Paulo, Brazil
Background
Lecithin cholesterol acyltransferase (LCAT) is involved in cholesterol metabolism. Familial LCAT deficiency (FLD) is a recessive disease associated with systemic lipid deposition, often resulting in CKD and fish-eye opacities.
Methods
Retrospective study, comprising clinical, laboratory and molecular genetic analyses of FLD patients.
Results
Twenty males and 18 females were diagnosed with FLD at an age of 38.6±16.4 yrs. Three pathogenic mutations in LCAT were identified: p.R268H, p.T298I and p.I227F, corresponding to distinct disease clusters. All patients had HDL-c <10mg/dL, ApoAI was 0.45±0.10g/L and ApoB 0.41±0.19g/L. Corneal opacities were seen in 36 cases; Scheimpflug densitometry revealed high corneal density in all 3 evaluated individuals. Anemia was present in 25 cases (Hb of 10.7±2.2g/dL) and hemolysis in 27. Increased resistance of red blood cells to osmotic stress was observed in all 5 evaluated patients. Estimated glomerular filtration rate (eGFR) displayed high intra- and interfamilial variability; 7 patients developed ESKD at an age of 38.3±14.2 yrs. Protein/creatinine ratio was 0.54g/g (p25-p75: 0.12-1.77) in nondialytic cases; 9 of 21 had hematuria. C3 was low in 1 patient while C4 was normal in all. Hypertension, present in most cases, was associated with age>30 yrs and eGFR<83mL/min/1.73m2 (OR 15.5). Coronary artery calcium score was zero in the 2 evaluated patients. Kidney biopsy revealed glomerular deposits (8/8 patients), glomerular sclerosis (7/8), endocapillary proliferation (4/8), glomerular basement membrane splitting (4/8), and interstitial fibrosis (<5-60%). Thrombotic microangiopathy (TMA) was detected in 3 cases and dominance/codominance of C3 mesangial deposits in all. Treatment included RAS inhibitors and statins.
Conclusion
The renal phenotypic variability suggests that environmental and/or genetic factors may modify CKD progression in FLD. Our findings suggest that, in addition to cholesterol deposition, TMA and C3 mesangial deposits may also contribute to renal injury, supporting a pathogenic role for activation of the alternative complement pathway.
Funding
- Government Support - Non-U.S.