MON-037 A RARE CASE: FAMILIAL MULTICENTRIC OSTEOLYSIS WITH NEPHROPATHY TREATED WITH TACROLIMUS

Abstract

Multicentric Carpo-Tarsal Osteolysis is an extremely rare genetic condition with variable inheritance. It is typically associated with progressive osteolysis and bone destruction. Five forms have been described in the literature, with varying nephropathy. We present a case of familial multicentric osteolysis, but with variable inheritance of the nephropathy. The patient (male) originally presented to the hospital aged 16 months with swelling and reduced function of his wrists. Ultrasound showed half of his carpal bones to be missing. His older brother had presented later in childhood with a similar bony phenotype. However, his older brother has none of the nephropathy phenotype. Both parents and his non-identical twin were unaffected. Our patient then presented to the nephrology service aged 3yrs with hypertension; 122/82mmHg (above the 99thcentile for age and height), mild peri-orbital edema, mild hypoalbuminemia (32 g/L) and significant albuminuria (316 mg/mmol). He was initially started on amlodipine to control his hypertension. His blood pressure improved, but his proteinuria persisted, and he was referred for a renal biopsy. His histology showed a complex mixed picture. Light microscopy showed focal segmental glomerulosclerosis (FSGS), with a number of poorly formed/atubular glomeruli. Immunofluorescence showed an immune complex glomerulonephritis. Electron microscopy showed highly abnormal glomerular basement membrane structure. The conclusion was an inherited glomerular basement membrane abnormality with superimposed immune-mediated glomerular disease, resembling membranous nephropathy. All other investigations, including autoimmune screen and renal ultrasound were normal. Following the biopsy, and with ongoing proteinuria, amlodipine was switched to enalapril. During this time, genetic testing demonstrated a pathogenic heterozygous mutation c.176C>Tp. (Pro59Leu) on the MAFB gene. The MAFB gene encodes for a basic leucine zipper transcription factor and is associated with multicentric osteolysis nephropathy and Duane retraction syndrome 3 (with or without deafness). Despite an increasing enalapril dose, his albuminuria persisted, ranging from 74.6 – 170.7 mg/mmol. His creatinine remained normal throughout, ranging from 27 – 38 ummol/L. One previous case described in the literature, used ciclosporin to successfully reduce the proteinuria, so it was decided to add tacrolimus. This reduced albuminuria to 49.3 mg/mmol within a month and increased serum albumin to 39 g/L. Within 6 months his urine dip was negative. Following a successful year of tacrolimus therapy, a trial off treatment was commenced. Within a month his albuminuria had increased to 105.1 mg/mmol, tacrolimus was re-introduced, and subsequent remission quickly achieved. To our knowledge this is only the second case in the literature of a calcineurin inhibitor being used successfully for this indication. We present a rare case of familial multicentric osteolysis which has had variable phenotypic penetrance within the same family. Our patient had a mixed biopsy picture and significant albuminuria which has been successfully treated with tacrolimus.