• PMID: 17507040
• Gene Name: TNF
• Condition: Male infertility, hypergonadotropic hypogonadism
• Association: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid dep
• Mutation: leucine-75-proline apolipoprotein A-I
• Population size: 10
• Population details: 10 presenting with infertility, gynecomastia, decreased libido, erectile dysfunction
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Nonobstructive azoospermia, macro-orchidism with or without hypogonadism

Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis

Scalvini T, Martini PR, Obici L, Tardanico R, Biasi L, Gregorini G, Scolari F, Merlini G.

PURPOSE: We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. MATERIALS AND METHODS: Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. RESULTS: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. CONCLUSIONS: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary. FAU - Scalvini, Tiziano AU - Scalvini T AD - Department of Endocrinology and Andrology, Spedali Civili, Brescia, Italy. FAU - Martini, Paola Rossana AU - Martini PR FAU - Obici, Laura AU - Obici L FAU - Tardanico, Regina AU - Tardanico R FAU - Biasi, Luciano AU - Biasi L FAU - Gregorini, Gina AU - Gregorini G FAU - Scolari, Francesco AU - Scolari F