Abstract: TH-PO531

Treatment of Nephrotic-Range Proteinuria with Tacrolimus in Mitochondrial Trifunctional Protein Deficiency

Session Information

  • Trainee Case Reports - I
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 1600 Pediatric Nephrology

Authors

  • Beng, Hostensia M., Children's National Health System and The George Washington University, Washington, District of Columbia, United States
  • Moudgil, Asha, Children's National Health System and The George Washington University, Washington, District of Columbia, United States
  • Ahn, Sun-Young, Children's National Health System and The George Washington University, Washington, District of Columbia, United States
Introduction

Mitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder of long-chain fatty acid oxidation that leads to lactic acidosis, recurrent rhabdomyolysis, cardiomyopathy, and hepatic dysfunction.

Case Description

A 7-month old girl, with known MTP deficiency, presented with poor oral intake and lethargy. Laboratory analysis revealed a low corrected serum calcium level of 6.6 mg/dl, elevated CK level of 14,080 U/L, and nephrotic range proteinuria with a urine protein to creatinine ratio (uPCR) of 7.6 mg/mg. Serum albumin was low at 2.8 g/dl and urine beta-2-microglobulin was mildly elevated at 556 mcg/g creatinine (nl <300 mcg/g). The patient was treated for primary hypoparathyroidism and rhabdomyolysis, known complications of MTP deficiency. Despite resolution of her rhabdomyolysis, she continued to have nephrotic range proteinuria and underwent a renal biopsy that demonstrated minimal change disease and foot process fusion. She was started on tacrolimus and her uPCR gradually normalized 8 months after treatment. She has continued to have normal renal function and uPCR values at the time of this report (2 years of age). The patient has an older sister with the same heterozygous deletion in the HADHB gene (c.1059delT), which is predicted to cause truncation and loss of long-chain-3-hydroxyacyl CoA dehydrogenase function, leading to MTP deficiency. This sister was diagnosed with nephrotic syndrome and focal segmental glomerulosclerosis at 18 months of age, and developed end stage renal disease at 20 months of age.

Discussion

Renal involvement has been reported in only 1 patient with MTP deficiency to date, the sister of our patient. The pathogenesis of proteinuria in the 2 siblings remains elusive. Given that other mitochondrial disorders, such as coenzyme Q10 deficiency, have been associated with nephrotic syndrome, the proteinuria may be related to their mitochondrial dysfunction. Calcineurin inhibitors have been reported to reduce proteinuria by stabilizing the podocyte actin cytoskeleton. Tacrolimus was an effective treatment for our patient, who has maintained normal renal function, unlike her sister. Further investigation will be needed to determine the role of calcineurin inhibitors in the treatment of nephrotic syndrome associated with mitochondrial disorders.