Endocrine profiling in black South African fanconi anaemia patients, homozygous for a fancg founder mutation
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Date
2019
Authors
Dillon, Bronwyn
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Abstract
Fanconi anaemia (FA) is an uncommon, phenotypically diverse, hereditary condition
associated most commonly with bone marrow failure, multiple physical congenital
abnormalities, and an increased susceptibility to the development of haematological
and solid tissue malignancies. Less recognised manifestations of FA include
endocrine abnormalities. International discourse has highlighted that these
abnormalities are widespread among individuals with FA. To date there has been no
systematic study that has evaluated the endocrine abnormalities in Black South
African patients with FA, particularly those homozygous for a founder mutation
(c.637_643delTACCGCC) in FANCG. The objectives of this research were to
evaluate endocrine gland function in Black South African patients with FA and a
single FA genotype, and to determine the frequency and nature of endocrine
abnormalities in this group. The study comprised of a cross-sectional, descriptive
study of 24 Black South African patients with FA (homozygous for a founder FANCG
mutation), between the ages of 2 years and 21 years, recruited from South African
tertiary academic hospitals. Measured outcomes included: growth, pubertal status,
endocrine hormone function (including screening of the growth hormone axis, thyroid
gland function, and glucose and insulin metabolism) and bone age. Endocrine
dysfunction was present in 70.8% (17 of 24) of the study cohort, including short
stature in 45.8% (11 of 24), abnormal IGF-1/IGFBP-3 in 25.0% (6 of 24), insulin
resistance in 41.7% (10 of 24), and abnormal thyroid function in 16.7% (4 of 24). No
abnormalities of glucose metabolism were identified. Abnormal pubertal status was
seen in three males (12.5% of the study cohort). Abnormal bone ages were present
in 34.8% (8 of 23) of the cohort, and abnormally fused carpal bones were present in
13.0% (3 of 23). It was concluded that endocrine abnormalities occur at a high
frequency in Black South African patients with FA, similar to other FA cohorts. Our
data are specific to FA patients with a single genotype, and therefore this provides
the first genotype-phenotype information on endocrine abnormalities in Black South
African patients, homozygous for a founder FANCG 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.
Description
A Research Report (in the format of a “submissible” paper) submitted to the Faculty
of Health Sciences, University of the Witwatersrand, Johannesburg, in partial
fulfillment of the requirements for the degree of Master of Medicine, in Medical
Genetics
Johannesburg, 2019