Transthyretin cardiac amyloidosis (ATTR-CA) is a form of restrictive cardiomyopathy characterized by the abnormal deposition of transthyretin in the myocardial interstitium, presenting with clinical manifestations such as heart failure, atrial fibrillation, and cardiac conduction system disorders. The significant individual variability in the symptomatology of ATTR-CA patients poses considerable challenges for precise diagnosis. This study provides a review of biomarkers associated with ATTR-CA and highlights the TTR tetramer as a potential novel indicator. The amyloid deposition in ATTR-CA is closely related to the dissociation of TTR tetramers; however, the TTR tetramer is not included among the biomarkers currently used in clinical practice. Investigating the concentration, profile, and dissociation rate of TTR tetramers holds profound significance for the early detection and prognostic assessment of ATTR-CA. This article synthesizes the research on traditional biomarkers of ATTR-CA and emphasizes the potential application value of TTR tetramers in disease diagnosis and prognostic evaluation.
ObjectiveTo investigate the causes of secondary glaucoma after vitrectomy for familial vitreous amyloidosis associated with transthyretin (TTR) gene Gly83Arg mutation.MethodsA retrospective case study. From January 2008 to January 2020, 13 cases (23 eyes) with hereditary vitreous amyloidosis and treated by vitrectomy in the Affiliated Hospital of Zunyi Medical University were collected. Among them, there were 7 males with 12 eyes and 6 females with 11 eyes. The average age was 43.0±4.8 years. All the affected eyes underwent standard three-channel vitrectomy through the flat part of the ciliary body. According to whether complete vitreous detachment (PVD) was formed during the operation, it was divided into complete PVD group and incomplete PVD group; according to the occurrence time of secondary glaucoma and vitreous amyloidosis after surgery, it was divided into 1-12 months group and 13-36 months group, ＞37 months group. The average follow-up time after surgery was 36.7±6.0 months. The incidence of secondary glaucoma and the recurrence rate of vitreous amyloidosis between groups were compared by χ2 test; the correlation between recurrence of vitreous amyloidosis and secondary glaucoma after surgery was analyzed by Spearman rank correlation analysis.ResultsAmong the 23 eyes, there were 8 eyes in the complete PVD group and 15 eyes in the incomplete PVD group, respectively. Vitreous amyloidosis recurred in 15 eyes (65.22%, 15/23) after surgery. There were 14 (93.30%, 14/15) and 1 (6.70%, 1/15) eyes in the incomplete PVD group and the complete PVD group, respectively; the comparison of the recurrence rate of vitreous amyloidosis between the two groups was statistically significant (χ2=11.676, P＜0.01). 1-12 months group, 13-36 months group, ＞37 months group included 1 (4.35%, 1/23), 12 (52.17%, 12/23), 2 (8.70%, 2/23) Only eye. The recurrence rate in the 13-36 months group was significantly higher than that in the 1-12 months group and ＞37 month group. Secondary glaucoma occurred in 11 eyes (47.80%, 11/23) after surgery. 1-12 months group, 13-36 months group, above 37 months group were 1 (4.35%, 1/23), 8 (34.78%, 8/23), 2 (8.70%, 2/23) eyes. The incidence of secondary glaucoma in the 13-36 months group was higher than that in the 1-12 months group and ＞37 months group. Among 11 eyes with secondary glaucoma, 10 eyes had recurrence of vitreous amyloidosis after surgery, and 1 eye had no recurrence. The results of Spearman rank correlation analysis showed that there was a positive correlation between the recurrence of vitreous amyloidosis and the occurrence of secondary glaucoma (rs=0.516, P=0.012).ConclusionThe incidence of secondary glaucoma after vitrectomy in a family with vitreous amyloidosis caused by the Gly83Arg mutation of TTR gene is higher, and its occurrence is significantly positively correlated with the recurrence of vitreous amyloidosis.
ObjectiveTo observe the clinical characteristics of patients with familial vitreous amyloidosis (FVA) and the efficacy of vitrectomy (PPV) and the occurrence of complications. MethodsA retrospective clinical study. From June 2009 to March 2020, 32 eyes of 18 patients from 3 FVA families who were diagnosed and treated by PPV at Department of Ophthalmology of Jiaxing TCM Hospital were included in the study. Among them, there were 12 males with 22 eyes and 6 females with 10 eyes. The average age of onset was 42.28±3.25 years; the average duration of disease was 3.75±3.93 years. All the affected eyes underwent best corrected visual acuity (BCVA) and B-mode ultrasound examination. A logarithmic visual acuity chart was used in the BCVA examination, which was converted to the logarithmic minimum angle of resolution (logMAR) visual acuity when recorded. The average logMAR BCVA of the affected eye was 1.72±0.53; the intraocular pressure was less than 21 mm Hg (1 mm Hg=0.133 kPa). The vitreous body of the affected eye was obviously cloudy. All the affected eyes underwent standard three-channel PPV through the flat part of the ciliary body, and vitreous specimens were collected for pathological examination during the operation. Peripheral venous blood of probands from 3 families was collected, and the whole exome gene sequencing was performed. The follow-up time after surgery was ≥6 months. The patient's clinical characteristics, fundus lesions in PPV, changes in BCVA after surgery, and complications was observed. One-way analysis of variance or t test was performed for measurement data comparison; χ2 test was performed for count data comparison. ResultsThe vitreous body of the affected eye showed gray-white dense and thick flocculent changes, and the posterior capsule attached to the lens showed "foot disc-like" turbidity; later the lens was mainly cystic opacity. Pathological examination of the vitreous body showed positive staining of Congo red; under a polarized light microscope, it showed apple green dots and sheet-like birefringence. The genetic test results showed that there was a c.307G>C (p.Gly103Arg) missense mutation in the TTR gene of the proband in Family 2. Peripheral retinal hemorrhages in 4 eyes (12.5%, 4/32), retinal tears in 5 eyes (15.6%, 5/32), retinal degeneration in 4 eyes (12.5%, 4/32), retinal detachment were found in PPV 3 eyes (9.4%, 3/32). The vitreous body was filled with C3F8 and silicone oil respectively for 2, 1 eye. Six months after the operation, the logMAR BCVA of the affected eye was 0.39±0.32, which was significantly higher than that before the operation, and the difference was statistically significant (t=15.131, P=0.000). After the operation, high intraocular pressure occurred in 2 eyes (6.3%, 2/32), secondary glaucoma in 1 eye (3.1%, 1/32), retinal detachment in 2 eyes (6.3%, 2/32), neovascular glaucoma (NVG) in 2 eyes (6.3%, 2/32), cataract in 10 eyes (31.3%, 10/32). ConclusionThe vitreous body of FVA eyes are gray-white dense, thick and flocculent, attached to the posterior lens capsule, showing "foot disc-like" turbidity; PPV treatment can effectively improve the BCVA of the FVA eyes; secondary glaucoma, secondary retinal detachment, NVG can occur after surgery.
ObjectiveTo observe the transthyretin (TTR) gene mutation, protein and mRNA expression in patients with familial vitreous amyloidosis. MethodsSubjects were divided into three groups: (1) illness group: seven patients with familial vitreous amyloidosis. (2) No-illness group: 9 unaffected family members. (3) Control group: 9 healthy individuals in same area. Subjects' peripheral venous blood were collected and DNA were extracted, 4 exons of TTR gene were amplified by reverse transcription polymerase chain reaction(RT-PCR), the gene fragments were sequencing by the fluorescence labelling method. Serum TTR protein expression was detected by Western blot, and TTR mRNA in leukocyte was assayed by RT-PCR. Results4 exons of TTR gene of all samples were amplified, and DNA sequencing data showed that 7 patients and 3 subjects DNA from unaffected family members had mutated in the 3rd exon of 107th base, changing from G to C. Heterozygous mutation occurred in codon of the 83th amino acid in exon 3, namely, Gly83Arg, resulted in the change of GGC to CGC. The protein and mRNA expression of TTR was lower in illness group than no-illness group and control groups(P < 0.05). Compared with control group, TTR mRNA expression in unaffected family members groups was significant decreased(P < 0.05). ConclusionHeterozygous mutation occurred in codon of the 83th amino acid in exon 3, namely Gly83Arg, and suggested that Gly83Arg is connected with the change of TTR mRNA and protein expression.