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Secondary amyloidosis in a patient carrying mutations in the familial Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS) genes.

Clementi A, Cruz DN, Granata A, Virzì GM, Battaglia G - Clin Kidney J (2013)

Bottom Line: AA amyloidosis may also complicate several hereditary diseases, where genetic factors play a pivotal role in the expression of amyloidosis.We describe a case of a 21-year-old Romanian woman who presented at the 35th week of gestation with acute abdominal pain, nausea and vomiting.The laboratory workup performed after delivery showed proteinuria in the nephrotic range and increased SAA protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Dialysis , San Giovanni Di Dio Hospital , Agrigento , Italy.

ABSTRACT
Secondary amyloidosis (AA) is characterized by the extracellular tissue deposition of fibrils composed of fragments of an acute-phase reactant protein, serum amyloid A (SAA), due to chronic inflammatory diseases, infections and several neoplasms. AA amyloidosis may also complicate several hereditary diseases, where genetic factors play a pivotal role in the expression of amyloidosis. Familial Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS) are the most frequently involved. We describe a case of a 21-year-old Romanian woman who presented at the 35th week of gestation with acute abdominal pain, nausea and vomiting. The laboratory workup performed after delivery showed proteinuria in the nephrotic range and increased SAA protein. Kidney amyloid deposits were detected and genetic testing for secondary amyloidosis was performed identifying two mutations, one involving the gene of FMF (MEFV), and the other involving the tumour necrosis factor receptor-1 gene (TNFRSF1A). To our knowledge, this is the first case in the literature where secondary amyloidosis develops in a patient carrying mutations involving the genes of both FMF and TRAPS.

No MeSH data available.


Related in: MedlinePlus

Kidney biopsy. Diffuse glomerular deposition of amorphous hyaline material, which stained weakly with periodic acid Shiff's (PAS) and bit Congo red (A and B). Interstitial amyloid deposits (C and D). See black arrows.
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SFT112F1: Kidney biopsy. Diffuse glomerular deposition of amorphous hyaline material, which stained weakly with periodic acid Shiff's (PAS) and bit Congo red (A and B). Interstitial amyloid deposits (C and D). See black arrows.

Mentions: Table 1 summarizes the laboratory examination performed after delivery. Proteinuria 3.6 g/24 h was noted, serum creatinine was 53 µmol/L (0.6 mg/dL) and urea 7.1 mmol/L (20 mg/dL). Haemoglobin was 78 g/L (7.8 g/dL), white blood cells 20 × 109/L (19.700/µL) with 94% of neutrophils and platelets 738 × 109/L (738.000/µL). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were 150 mg/L and 90 mm/h, respectively; fibrinogen was normal. Serum protein was 33 g/L (3.3 gr/dL) and albumin 16 g/L (1.6 g/dL). No monoclonal band was present in serum protein electrophoresis. Autoimmune and coagulation parameters were normal, as well as thyroid and liver function tests. Hepatitis B virus infection markers were negative, and apart from a slight increase in hepatitis C virus antibody titre, no signs of active hepatitis were detected. The SAA protein level was high (591.28 ng/mL). Abdominal ultrasonography showed hyperechogenic cortex. Echocardiography revealed only mild mitral regurgitation. Electromyography detected initial signs of lower-limb sensory neuropathy. While abdominal fat pad aspirate was negative for amyloidosis, kidney biopsy revealed a diffuse glomerular deposition of amorphous hyaline material that stained weakly with periodic acid Shiff's and bound Congo red and thioflavine T (Figure 1). Vascular and tubular deposits were also present. Rectal biopsy was performed as well, showing the presence of A protein and the absence of immunoglobulin light chains. Molecular genetic screening tests for secondary (AA) amyloidosis were performed. A blood sample was obtained from the patient after her informed consent and genomic DNA was extracted from peripheral blood lymphocytes. The entire coding regions and intron–exon junctions, which are important in order to identify variants affecting mRNA splicing, were amplified and screened for mutation in Apo A-I, TNFRS1A and MEFV genes by the Sanger sequencing method to identify the causing mutation. Reference sequences were obtained from NCBI RefSeq and all sequences were compared with these sequences. The standard nomenclature recommended by HGVS was used to number nucleotides and name mutations or variants. Two different mutations were identified by sequencing analysis. The first involved a copy of the gene of the FMF (MEFV) and it was c2082G>A, p.M694I on the short arm of chromosome 16. The second involved a copy of the tumour necrosis factor receptor-1 gene (TNFRSF1A), and it was c.362G>A, p.R92Q on the short arm of chromosome 12 (Figure 2). The diagnosis of AA amyloidosis was then confirmed. The Apo A-I gene did not present any mutations.Table 1.


Secondary amyloidosis in a patient carrying mutations in the familial Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS) genes.

Clementi A, Cruz DN, Granata A, Virzì GM, Battaglia G - Clin Kidney J (2013)

Kidney biopsy. Diffuse glomerular deposition of amorphous hyaline material, which stained weakly with periodic acid Shiff's (PAS) and bit Congo red (A and B). Interstitial amyloid deposits (C and D). See black arrows.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842151&req=5

SFT112F1: Kidney biopsy. Diffuse glomerular deposition of amorphous hyaline material, which stained weakly with periodic acid Shiff's (PAS) and bit Congo red (A and B). Interstitial amyloid deposits (C and D). See black arrows.
Mentions: Table 1 summarizes the laboratory examination performed after delivery. Proteinuria 3.6 g/24 h was noted, serum creatinine was 53 µmol/L (0.6 mg/dL) and urea 7.1 mmol/L (20 mg/dL). Haemoglobin was 78 g/L (7.8 g/dL), white blood cells 20 × 109/L (19.700/µL) with 94% of neutrophils and platelets 738 × 109/L (738.000/µL). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were 150 mg/L and 90 mm/h, respectively; fibrinogen was normal. Serum protein was 33 g/L (3.3 gr/dL) and albumin 16 g/L (1.6 g/dL). No monoclonal band was present in serum protein electrophoresis. Autoimmune and coagulation parameters were normal, as well as thyroid and liver function tests. Hepatitis B virus infection markers were negative, and apart from a slight increase in hepatitis C virus antibody titre, no signs of active hepatitis were detected. The SAA protein level was high (591.28 ng/mL). Abdominal ultrasonography showed hyperechogenic cortex. Echocardiography revealed only mild mitral regurgitation. Electromyography detected initial signs of lower-limb sensory neuropathy. While abdominal fat pad aspirate was negative for amyloidosis, kidney biopsy revealed a diffuse glomerular deposition of amorphous hyaline material that stained weakly with periodic acid Shiff's and bound Congo red and thioflavine T (Figure 1). Vascular and tubular deposits were also present. Rectal biopsy was performed as well, showing the presence of A protein and the absence of immunoglobulin light chains. Molecular genetic screening tests for secondary (AA) amyloidosis were performed. A blood sample was obtained from the patient after her informed consent and genomic DNA was extracted from peripheral blood lymphocytes. The entire coding regions and intron–exon junctions, which are important in order to identify variants affecting mRNA splicing, were amplified and screened for mutation in Apo A-I, TNFRS1A and MEFV genes by the Sanger sequencing method to identify the causing mutation. Reference sequences were obtained from NCBI RefSeq and all sequences were compared with these sequences. The standard nomenclature recommended by HGVS was used to number nucleotides and name mutations or variants. Two different mutations were identified by sequencing analysis. The first involved a copy of the gene of the FMF (MEFV) and it was c2082G>A, p.M694I on the short arm of chromosome 16. The second involved a copy of the tumour necrosis factor receptor-1 gene (TNFRSF1A), and it was c.362G>A, p.R92Q on the short arm of chromosome 12 (Figure 2). The diagnosis of AA amyloidosis was then confirmed. The Apo A-I gene did not present any mutations.Table 1.

Bottom Line: AA amyloidosis may also complicate several hereditary diseases, where genetic factors play a pivotal role in the expression of amyloidosis.We describe a case of a 21-year-old Romanian woman who presented at the 35th week of gestation with acute abdominal pain, nausea and vomiting.The laboratory workup performed after delivery showed proteinuria in the nephrotic range and increased SAA protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Dialysis , San Giovanni Di Dio Hospital , Agrigento , Italy.

ABSTRACT
Secondary amyloidosis (AA) is characterized by the extracellular tissue deposition of fibrils composed of fragments of an acute-phase reactant protein, serum amyloid A (SAA), due to chronic inflammatory diseases, infections and several neoplasms. AA amyloidosis may also complicate several hereditary diseases, where genetic factors play a pivotal role in the expression of amyloidosis. Familial Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS) are the most frequently involved. We describe a case of a 21-year-old Romanian woman who presented at the 35th week of gestation with acute abdominal pain, nausea and vomiting. The laboratory workup performed after delivery showed proteinuria in the nephrotic range and increased SAA protein. Kidney amyloid deposits were detected and genetic testing for secondary amyloidosis was performed identifying two mutations, one involving the gene of FMF (MEFV), and the other involving the tumour necrosis factor receptor-1 gene (TNFRSF1A). To our knowledge, this is the first case in the literature where secondary amyloidosis develops in a patient carrying mutations involving the genes of both FMF and TRAPS.

No MeSH data available.


Related in: MedlinePlus