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Testicular Involvement is a Hallmark of Apo A-I Leu75Pro Mutation Amyloidosis
Andrea Delbarba1, Paolo Facondo2, Simona Fisogni3
1Unit of Endocrinology and Metabolism, ASST Spedali Civili Brescia, Brescia, Italy.
Context:
Apo A-I Leu75Pro is a rare hereditary form of amyloidosis that mainly involves the kidney, the liver, and the testis.
Objective:
To define the characteristics of organ damage and testis impairment in the largest cohort collected to date of men with Apo A-I Leu75Pro amyloidosis.
Design, Setting, And Patients:
Retrospective study from a prospectively collected database of 129 male subjects >18 years with Apo A-I Leu75Pro amyloidosis from a reference center at the University Hospital of Brescia, Italy.
Main Outcome Measures:
We evaluated liver and renal function, scrotal ultrasound, reproductive hormone levels, testis biopsy, hypogonadal symptoms, and fertility.
Results:
Progressive involvement of testis, kidney, and liver was observed in 96/129 (74.4%) cases. Testis impairment was found in 88/129 patients (68.2%), liver in 59 (45.7%) and renal in 50 (38.8%). Testis damage was often the first manifestation of the disease and the only dysfunction in 30% of younger patients (<38 years). Testicular involvement was characterized mainly by primary (73/88 patients, 83.0%) and subclinical (8/88, 9.1%) hypogonadism. Almost all (85/88, 96.6%) also had high follicle-stimulating hormone, suggesting a primary global damage of endocrine and spermatogenic functions, and 30% of them did not conceive. Macroorchidism was found in 53/88 (60.2%) patients, especially in men <54 years (30/33, 90.9%). Apo A-I amyloid deposits were found in Sertoli cells, germinal epithelium, and vessel walls.
Conclusion:
In men with Apo A-I Leu75Pro amyloidosis, testicular involvement is the hallmark of the disease, characterized by global primary testicular dysfunction and macroorchidism due to amyloid deposits.
Insights
Apo A-I Leu75Pro amyloidosis primarily affects the testes, causing dysfunction and enlargement. This rare hereditary condition often presents with testicular issues first, impacting fertility and hormone levels.
Area of Science:
- Nephrology
- Endocrinology
- Genetics
Background:
- Apo A-I Leu75Pro amyloidosis is a rare hereditary disease.
- It primarily affects the kidneys, liver, and testes.
Purpose of the Study:
- To characterize organ damage and testicular impairment in men with Apo A-I Leu75Pro amyloidosis.
- To analyze the largest cohort to date.
Main Methods:
- Retrospective study of 129 male patients.
- Evaluated liver and renal function, scrotal ultrasound, hormone levels, testis biopsy, hypogonadal symptoms, and fertility.
Main Results:
- Testicular involvement (68.2%) was common, often the first sign, and characterized by primary hypogonadism (83.0%) and macroorchidism (60.2%).
- Kidney (38.8%) and liver (45.7%) involvement also observed.
- Amyloid deposits found in testicular cells and vessel walls.
Conclusions:
- Testicular involvement is the hallmark of Apo A-I Leu75Pro amyloidosis in men.
- Characterized by global primary testicular dysfunction and macroorchidism due to amyloid deposits.
