The proband is a 39-year-old South Asian female of Indian origin who was diagnosed with systemic amyloidosis of unknown type when she was 16 years of age. At the time of diagnosis, she was pregnant and was experiencing gastrointestinal symptoms of abdominal bloating, dyspepsia, heartburn, and nausea. These symptoms persisted postpartum, and the patient underwent an upper endoscopy with biopsy, which was consistent with the presence of amyloid material; however, the type could not be determined. Thereafter, the patient continued to live a fairly normal life and did not seek any further medical attention until her daughter who when turned 16 started experiencing similar symptoms and underwent an upper endoscopy with biopsy results consistent with the presence of amyloid. At that time, the family sought medical attention at our institute. The proband reported that, in spite of an overall normal life, she had continued to experience dyspeptic symptoms that worsened with stress. She also reported around 12-15 episodes of hematemesis since her initial diagnosis. Additional symptoms on close questioning included easy bruisability, periorbital purpura, and ecchymosis associated with activities such as retching and vomiting. An upper endoscopy was performed at the Mayo Clinic. No morphological abnormality was seen on the endoscopy; however, Congo red stain demonstrated the presence of amyloid material in the gastroesophageal junction, stomach, and duodenum. Serum and urine protein electrophoresis were normal. Proteomic assessment with laser capture mass spectrometry (LCMS) evaluation of the congophilic material detected an amino acid sequence abnormality in the lysozyme protein (I56T). Peripheral blood genotyping confirmed I56T mutation (DNA change c.221T > C) in exon 2 of the lysozyme gene, which replacing isoleucine with threonine at position 56. I56T mutation per human genome variation society (HGVS) nomenclature is now known as I74T. Patient's renal and hepatic functions were normal, and she did not have any adenopathy. Besides iron deficiency and mildly delayed gastric emptying, no other abnormality was noted. The patient continues with yearly follow-up in our amyloidosis clinic with periodic exacerbations of dyspeptic symptoms and a few episodes of small-volume hematemesis, which have responded to high-dose acid suppressive treatment.
Proband's daughter at 16 year of age started experiencing anxiety and upper abdominal pain along with dyspeptic symptoms, which lead to an upper GI tract endoscopy and biopsy confirming I56T mutant Alys via LCMS. Her most significant symptoms were indigestion, anorexia, altered bowel habits, and easy bruisability. She was also noted to have moderate iron deficiency anemia secondary to heavy menstruation. Her symptoms subsequently improved with change in dietary habits. At the time of most recent evaluation, which was a year ago, the patient has been doing relatively well with the exception of intermittent nausea and abdominal bloating.