AA amyloidosis revealing mevalonate kinase deficiency: A report of 20 cases including two new French cases and a comprehensive review of literature.

Abstract

INTRODUCTION:

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease that can lead to an inflammatory A amyloidosis (AA).

METHODS:

To study the occurrence of AA in MKD patients we performed a systemic review of the literature and described two novel patients.

RESULTS:

Amyloidosis occurred in 20 MKD patients, renal impairment being always the revealing symptom of AA. Although an accurate prevalence estimation is not possible since exact MKD prevalence is unknown, AA seems rare in MKD (about 6% if we estimate MKD prevalence at 300 patients worldwide). MVK gene study, available in 18 out of the 20 patients, confirmed two pathogenic mutations in all tested individuals. The most frequent genotype was V377I/I268T (n = 9/18). Retrospective search of clinical signs of MKD established, in all patients carrying MVK pathogenic mutations, a disease onset within the first four years of life. Nephrotic syndrome (n = 15), end-stage renal failure (n = 5) or both (n = 8) pointed out kidney amyloidosis. The youngest patient with renal amyloidosis was a European four-year-old girl previously misdiagnosed with PFAPA syndrome. Five patients died of AA amyloidosis despite the use of a biotherapy for two of them; kidney transplant was performed in nine individuals. Colchicine was not effective in any patient. Anti-interleukin-1 anakinra (n = 8), anti TNF etanercept (n = 7) and anti-interleukin 6 tocilizumab (n = 5) treatments were partially effective.

CONCLUSION:

Inflammatory A amyloidosis, a rare complication of MKD, can cause death or necessitate kidney transplantation. Early diagnosis and cytokine blocking biotherapy using anti-IL1, anti-TNF or anti-IL6 agents are required to prevent terminal renal failure.

• Authors: François Rodrigues, Jean-Baptiste Philit, Irina Giurgea, Dany Anglicheau, Jean-Jacques Roux, Nadia Hoyeau, Gilles Grateau, Laurence Cuisset, Sophie Georgin-Lavialle
• Journal: Seminars in arthritis and rheumatism (Semin Arthritis Rheum) Vol. 50 Issue 6 Pg. 1370-1373 (12 2020) ISSN: 1532-866X [Electronic] United States
• PMID: 32252977 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Tumor Necrosis Factor Inhibitors

Topics

• Amyloidosis (complications, diagnosis)
• Child, Preschool
• Female
• Genotype
• Humans
• Mevalonate Kinase Deficiency (complications, diagnosis, drug therapy)
• Retrospective Studies
• Tumor Necrosis Factor Inhibitors