Endocrine phenotype of children and adults with Fanconi anemia

Rose, Susan R.; Myers, Kasiani C.; Rutter, Meilan M.; Mueller, Robin; Khoury, Jane; Mehta, Parinda A.; Harris, Richard E.; Davies, Stella M.

doi:10.1002/pbc.24095

Cited by 38 publications

(77 citation statements)

References 31 publications

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“…However, age had no influence on occurrence of hypothyroidism in our FA HCT group. This may reflect a high rate of hypothyroidism at baseline in patients with FA, as incidence has ranged from 36% to 65% in mixed cohorts of patients with FA who had and who had not undergone transplantation [21–23]. Younger FA HCT patients were found to be of short stature much more often than older patients.…”

Section: Discussionmentioning

confidence: 99%

“…The studies had an aggregate of 28 patients who underwent HCT [21–23]. Rose et al [21] reported the endocrine phenotype of 61 children who did not undergo transplantation with FA: hypothyroidism was seen in 60%, hypogonadism in 0%, short stature in 61%, and low BMD (Z score < −2 SD) in 5%. Of the 17 pediatric HCT recipients, 65% had hypothyroidism, 25% had hypogonadism, 56% had short stature, and none had low BMD.…”

Section: Discussionmentioning

confidence: 99%

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Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation

Barnum

Petryk

Zhang

et al. 2016

Biology of Blood and Marrow Transplantation

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A number of endocrinopathies have been described after hematopoietic cell transplantation (HCT), but data are limited in patients with Fanconi anemia (FA). We report several endocrine-based disorders in a cohort of 44 patients with FA after HCT compared with both 74 patients who received HCT for hematologic malignancies and with 275 healthy controls. Endocrinopathies assessed included hypothyroidism, hypogonadism, short stature, dyslipidemia, insulin resistance, abnormalities in body composition, and bone health. Most (86%) patients with FA had at least 1 endocrinopathy, with 11% having 3 or more. Hypothyroidism was seen in 57%, hypogonadism in 27%, short stature in 50%, and reduced total body and lumbar spine bone mineral density (BMD) (height adjusted Z-score < −1) in 57% and 21%, respectively. Vitamin D deficiency was seen in 71%. Short stature was associated with younger age at HCT and gonadal failure was associated with older age at HCT. Insulin resistance was associated with increased percent fat mass and increased android/gynoid ratio by dual energy X-ray absorptiometry. Hypothyroidism, short stature, and reduced total body BMD were more prevalent in patients with FA compared with patients with hematologic malignancies. We recommend an assessment before transplantation and close follow-up afterwards to ensure proper clinical management. Future studies should continue to explore the impact of HCT on endocrinopathies in FA patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation

Barnum

Petryk

Zhang

et al. 2016

Biology of Blood and Marrow Transplantation

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“…Similarly, endocrinopathies are common in FA patients with 80% demonstrating short stature, glucose intolerance, dyslipidemia, hypothyroidism, hypogonadism, pubertal delay and impaired fertility [115, 116]. With improved long-term survival after alloHCT, there are greater efforts to quantify and ameliorate the late effects of these endocrinopathies [117].…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations

Ebens

MacMillan

Wagner

2016

Expert Review of Hematology

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“…Although F ko M ko mice do not show overt pancytopenia, they exhibit an increased incidence of other clinical traits associated with human FA. Short stature due to impaired postnatal growth is a common feature of individuals with FA (50,51). Furthermore, the microcephaly, ocular deformities, frontonasal dysplasia and mandibular micrognathism in F ko M ko mice phenocopy disease traits in some FA individuals (52–54).…”

Section: Discussionmentioning

confidence: 99%

Fanconi anemia signaling and Mus81 cooperate to safeguard development and crosslink repair

Larin

Gallo

Tamblyn

et al. 2014

Nucleic Acids Research

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Individuals with Fanconi anemia (FA) are susceptible to bone marrow failure, congenital abnormalities, cancer predisposition and exhibit defective DNA crosslink repair. The relationship of this repair defect to disease traits remains unclear, given that crosslink sensitivity is recapitulated in FA mouse models without most of the other disease-related features. Mice deficient in Mus81 are also defective in crosslink repair, yet MUS81 mutations have not been linked to FA. Using mice deficient in both Mus81 and the FA pathway protein FancC, we show both proteins cooperate in parallel pathways, as concomitant loss of FancC and Mus81 triggered cell-type-specific proliferation arrest, apoptosis and DNA damage accumulation in utero. Mice deficient in both FancC and Mus81 that survived to birth exhibited growth defects and an increased incidence of congenital abnormalities. This cooperativity of FancC and Mus81 in developmental outcome was also mirrored in response to crosslink damage and chromosomal integrity. Thus, our findings reveal that both pathways safeguard against DNA damage from exceeding a critical threshold that triggers proliferation arrest and apoptosis, leading to compromised in utero development.

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Endocrine phenotype of children and adults with Fanconi anemia

Abstract: We have evaluated in detail children and adults with FA for their growth and endocrine function. Overall, 79% of children and adults with FA had one or more endocrine abnormality.

Cited by 38 publications

References 31 publications

Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation

Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations

Fanconi anemia signaling and Mus81 cooperate to safeguard development and crosslink repair

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