Azoospermia as a new feature of Fabry disease

Papaxanthos-Roche, Aline; Déminière, C.; Bauduer, Frédéric; Hocké, C.; Mayer, Guy; Lacombe, Didier

doi:10.1016/j.fertnstert.2006.11.036

Cited by 13 publications

(11 citation statements)

References 13 publications

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“…Testicular biopsies performed in two infertile men suffering from FD with azoospermia revealed characteristic aspects of trihexoside ceramide (Gb 3 ) deposits in Leydig cells by optical and electronic microscopic analysis [168]. …”

Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,010

1,230

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.

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Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,010

1,230

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“…In particular, there have been several pathology-focused case reports of males with azoospermia and FD, males with storage of GL3 in testicular biopsies, and diminished fertility and FD (de Groot 1964;Guin et al 1976;Lacombe et al 2010;Papaxanthos-Roche et al 2007;T€ or€ ok et al 1980). The most informative case report focused on biopsies from a deceased 32-year-old male with FD.…”

Section: Introductionmentioning

confidence: 99%

“…As reported, biopsies revealed multiple areas of significant GL3 storage (Leydig cells, epithelial of ductuli efferentes, ductus of the epididymis, testicular interstitium, and seminiferous tubules) but undisturbed fertility in the patient despite the reduced diameter of the seminiferous tubules (Nistal et al 1983). In a separate report on two testicular biopsies which found storage of GL3 in the Leydig cells by optic and electronic microscopic analysis in two individuals with azoospermia and FD, authors suggest male patients desiring children may need to use assisted reproductive technologies such as testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) (Papaxanthos-Roche et al 2007;Lacombe et al 2010;T€ or€ ok et al 1980).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Fabry Disease on Reproductive Fitness

et al. 2017

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Fabry disease (FD) is a pan-ethnic, X-linked, progressive lysosomal storage disorder caused by pathogenic mutations in the GLA gene. Published case reports and abstracts suggest that decreased reproductive fitness may occur in males with FD. In order to understand the impact of FD on reproductive fitness and increase the accuracy of reproductive genetic counseling, this study examines a large, multi-centered population of individuals with FD to determine if males have reduced reproductive fitness. Study data were collected on 376 patients through two, gender-specific surveys distributed across the United States and Canada. The number of biological live-born children among individuals with FD was compared to statistics from the general population. Information was also collected on reduced sperm count, depression, pain, use of assisted reproductive technology, and reproductive choice. On average, females affected by FD had more biological live-born children (1.8) than males affected by FD (1.1). However, males affected by FD had an increased mean number of biological children (1.1) compared to the mean number of biological children fathered by men in the United States (0.9). Sixteen of the 134 males with FD reported oligospermia, which suggests that an infertility work up may be indicated for males having difficulty impregnating their partners. In our large multicenter sample, males and females with FD do not exhibit reduced reproductive fitness; on average they have more biological children than the general population in the United States. This information should assist clinicians in providing accurate reproductive genetic counseling and treatment for individuals with FD.

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“…Unlike the characteristic features and symptoms of FD, reproductive health issues have only been reported in individual case reports and not examined systematically in a large FD population. In particular, there have been several pathology-focused case reports of males with azoospermia and FD, males with storage of GL3 in testicular biopsies, and diminished fertility and FD (de Groot 1964;Guin et al 1976;Lacombe et al 2010;Papaxanthos-Roche et al 2007;T€ or€ ok et al 1980). The most informative case report focused on biopsies from a deceased 32-year-old male with FD.…”

Section: Introductionmentioning

confidence: 99%