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. 2020 Aug;8(8):e1351.
doi: 10.1002/mgg3.1351. Epub 2020 Jun 11.

Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation

Bronwyn Dillon  1 , Candice Feben  1 , David Segal  2 , Johannes du Plessis  3 , David Reynders  4 , Rosalind Wainwright  5 , Janet Poole  6 , Amanda Krause  1
Affiliations

Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation

Bronwyn Dillon et al. Mol Genet Genomic Med. 2020 Aug.

Abstract

Background: Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highlighted that these abnormalities are widespread among children and adults with FA. To date there has been no systematic study that has evaluated the endocrine abnormalities in a cohort of patients with FA, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG. The objectives of the study were to evaluate endocrine gland function in patients with FA of a single FA genotype, and to determine the frequency and nature of endocrine abnormalities in this group.

Methods: Cross-sectional, descriptive study of 24 South African patients of African ancestry with FA (homozygous for a FANCG founder mutation). Outcomes measured included growth, pubertal status, growth hormone axis screening, thyroid gland function, glucose and insulin metabolism and bone age (BA).

Results: Endocrine dysfunction was present in 70.8% (17 of 24), including abnormal insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 3 (IGFBP-3) in 25.0% (6 of 24), insulin resistance in 41.7% (10 of 24), abnormal thyroid function in 16.7% (4 of 24) and short stature in 45.8% (11 of 24). No abnormalities of glucose metabolism were identified. Abnormal pubertal status was seen in three males (12.5%). Abnormal BAs were present in 34.8% (8 of 23).

Conclusion: Endocrine abnormalities occur at a high frequency in patients with FA, homozygous for a FANCG founder mutation, similar to other FA cohorts. Our data are specific to FA patients with a single genotype, and therefore provide the first genotype-phenotype information on endocrine abnormalities in South African patients, homozygous for a FANCG founder mutation. Recommendations regarding endocrine screening in this patient subgroup are made, including, but not limited to, baseline testing of thyroid function, fasted insulin and glucose, and IGF-1 and IGFBP-3.

Keywords: FANCG; endocrine abnormalities; founder mutation; short stature; thyroid function.

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Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

FIGURE 1
FIGURE 1
Growth measurement distribution of patients with Fanconi anemia, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG (N = 24)
FIGURE 2
FIGURE 2
Endocrine abnormalities in patients with Fanconi anemia, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG (N = 24). Overt hypothyroidism refers to increased TSH and decreased FT4 (Garber et al., 2012); subclinical hypothyroidism refers to Increased TSH and normal FT4 (Garber et al., 2012); impaired fasting glucose refers to a laboratory fasting blood glucose reference greater than 6.0 mmol/L; insulin resistance was determined by a HOMA index greater than two. FT4, free thyroxine; GH, growth hormone; HOMA, homeostasis model assessment; TSH, thyroid stimulating hormone
FIGURE 3
FIGURE 3
Left hand and wrist anteroposterior X‐rays of three male patients with Fanconi anemia, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG, demonstrating fusion of the triquetral and lunate carpal bones. Fusion of the carpal bones is indicated by the arrows
See this image and copyright information in PMC

References

    1. Allen, D. B. (1996). Growth suppression by glucocorticoid therapy. Endocrinology and Metabolism Clinics of North America, 25(3), 699–717. 10.1016/S0889-8529(05)70348-0 - DOI - PubMed
    1. American Diabetes Association . (2019). Standards of medical care in diabetes – 2019 position statement. Diabetes Care, 37(1), 11–34. - PMC - PubMed
    1. Carel, J. C. , & Léger, J. (2008). Precocious puberty. NEJM., 358(22), 2366–2377. 10.1056/NEJMcp0800459 - DOI - PubMed
    1. Elder, D. A. , D’Alessio, D. A. , Eyal, O. , Mueller, R. , Smith, F. O. , Kansra, A. R. , & Rose, S. R. (2008). Abnormalities in glucose tolerance are more common in children with Fanconi anemia and associated with impaired insulin secretion. Pediatric Blood & Cancer, 51(2), 256–260. 10.1002/pbc.21589 - DOI - PubMed
    1. Emmaneul, M. , & Bokor, B. (2019).Tanner stages. NCBI StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK470280/ - PubMed

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