Abstract: Two Familial Cases with Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Caused by a Non-Cysteine Mutation (T50M) in the TNFRSF1A Gene Associated with Severe Multiorganic Amyloidosis

Two Familial Cases with Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Caused by a Non-Cysteine Mutation (T50M) in the TNFRSF1A Gene Associated with Severe Multiorganic Amyloidosis

TILMANN KALLINICH, SONIA BRIESE, JOACHIM ROESLER, BIRGIT RUDOLPH, NANETTE SARIOGLU, OLIVER BLANKENSTEIN, ROLF KEITZER, UWE QUERFELD, and DIETER HAFFNER

ABSTRACT.

An adolescent boy had had recurrent episodes of fever, abdominal pain, and arthralgias since the age of 7 years. Progressive renal failure due to renal amyloidosis developed, leading to renal transplant at the age of 14.5 years. Five years later, he developed AA amyloidosis in the transplant as well as the thyroid gland. His father had had similar symptoms including systemic amyloidosis since the age of 6 years. DNA sequence analysis revealed a heterozygous mutation in the TNFRSF1A (TNFa-receptor 1) gene (T50M) in both father and son causing tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Previous phenotype/genotype analyses have proposed that this mutation is usually not associated with the occurrence of amyloidosis. This difference in the clinical course in different families may indicate a strong influence of modifier genes. Treatment with a TNFRSF1B fusion protein TNF antagonist (etanercept) favorably influenced the disease course. (J Rheumatol 2004;31:2519-22)

Key Indexing Terms:

HEREDITARY PERIODIC FEVER SYNDROMES
AMYLOIDOSIS
ETANERCEPT
NONSTEROIDAL
RENAL TRANSPLANT

From the Department of Pediatric Nephrology, Pulmonology and Immunology; Department of Pathology; Department of Paidopathology; and Department of Pediatric Endocrinology, Charité Children's Hospital, Humboldt University, Berlin; and the Department of Pediatrics, University Hospital Dresden, Dresden, Germany.

T. Kallinich, MD; R. Keitzer, MD, Department of Pediatrics, Pulmonology and Immunology; S. Briese, MD; U. Querfeld, MD; D. Haffner, MD, Department of Pediatric Nephrology; B. Rudolph, MD, Department of Pathology; N. Sarioglu, MD, Department of Paidopathology; O. Blankenstein, MD, Department of Pediatric Endocrinology, Charité Children's Hospital; J. Roesler, MD, Department of Pediatrics, University Hospital Dresden.

Address reprint requests to Dr. D. Haffner, Department of Pediatric Nephrology, Charité Children's Hospital, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail:dieter.haffner@charite.de

Submitted July 28, 2003; revision accepted July 5, 2004.