Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To <i>PTF1A</i> Enhancer Mutations
<h3>Context</h3><p dir="ltr">Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with loss-of-function PTF1A mutations. Their clinical phenotype and disease p...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , , , , , , , , |
| منشور في: |
2020
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| الملخص: | <h3>Context</h3><p dir="ltr">Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with loss-of-function PTF1A mutations. Their clinical phenotype and disease progression have not been well characterized.</p><h3>Objective</h3><p dir="ltr">To evaluate phenotype and genotype characteristics and long-term follow-up of patients with PTF1A enhancer mutations.</p><h3>Setting</h3><p dir="ltr">Twelve tertiary pediatric endocrine referral centers.</p><h3>Patients</h3><p dir="ltr">Thirty patients with diabetes caused by PTF1A enhancer mutations. Median follow-up duration was 4 years.</p><h3>Main Outcome Measures</h3><p dir="ltr">Presenting and follow-up clinical (birthweight, gestational age, symptoms, auxology) and biochemical (pancreatic endocrine and exocrine functions, liver function, glycated hemoglobin) characteristics, pancreas imaging, and genetic analysis.</p><h3>Results</h3><p dir="ltr">Five different homozygous mutations affecting conserved nucleotides in the PTF1A distal enhancer were identified. The commonest was the Chr10:g.23508437A>G mutation (n = 18). Two patients were homozygous for the novel Chr10:g.23508336A>G mutation. Birthweight was often low (median SDS = –3.4). The majority of patients presented with diabetes soon after birth (median age of diagnosis: 5 days). Only 2/30 presented after 6 months of age. All patients had exocrine pancreatic insufficiency. Five had developmental delay (4 mild) on long-term follow-up. Previously undescribed common features in our cohort were transiently elevated ferritin level (n = 12/12 tested), anemia (19/25), and cholestasis (14/24). Postnatal growth was impaired (median height SDS: –2.35, median BMI SDS: –0.52 SDS) with 20/29 (69%) cases having growth retardation.</p><h3>Conclusion</h3><p dir="ltr">We report the largest series of patients with diabetes caused by PTF1A enhancer mutations. Our results expand the disease phenotype, identifying recurrent extrapancreatic features which likely reflect long-term intestinal malabsorption.</p><h2>Other Information</h2><p dir="ltr">Published in: The Journal of Clinical Endocrinology & Metabolism<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1210/clinem/dgaa613" target="_blank">https://dx.doi.org/10.1210/clinem/dgaa613</a></p> |
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