Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation
Abstract
:1. Introduction
2. Case Description
3. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Gosmain, Y.; Cheyssac, C.; Masson, M.H.; Guerardel, A.; Poisson, C.; Philippe, J. Pax6 Is a Key Component of Regulated Glucagon Secretion. Endocrinology 2012, 153, 4204–4215. [Google Scholar] [CrossRef] [Green Version]
- Guemes, M.; Rahman, S.A.; Kapoor, R.R.; Flanagan, S.; Houghton, J.A.L.; Misra, S.; Oliver, N.; Dattani, M.T.; Shah, P.T. Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management. Rev. Endocr. Metab. Dis. 2020, 21, 577–597. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cvekl, A.; Callaerts, P. PAX6: 25th anniversary and more to learn. Exp. Eye Res. 2017, 156, 10–21. [Google Scholar] [CrossRef]
- Mirrahimi, M.; Sabbaghi, H.; Ahmadieh, H.; Jahanmard, M.; Hassanpour, K.; Suri, F. A novel PAX6 Mutation Causes Congenital Aniridia with or without Retinal Detachment. Ophthalmic Genet. 2019, 40, 146–149. [Google Scholar] [CrossRef] [PubMed]
- Yasuda, T.; Kajimoto, Y.; Fujitani, Y.; Watada, H.; Yamamoto, S.; Watarai, T.; Umayahara, Y.; Matsuhisa, M.; Gorogawa, S.; Kuwayama, Y.; et al. PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Diabetes 2002, 51, 224–230. [Google Scholar] [CrossRef] [Green Version]
- Gosmain, Y.; Katz, L.S.; Masson, M.H.; Cheyssac, C.; Poisson, C.; Philippe, J. Pax6 is crucial for β-cell function, insulin biosynthesis, and glucose-induced insulin secretion. Mol. Endocrinol. 2012, 26, 696–709. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015, 17, 405–424. [Google Scholar] [CrossRef] [PubMed]
- Qiu, J.-J.; Zhang, Q.; Geng, Z.-x.; Liu, M.; Zhong, Z.-l.; Chen, J.-j.; Liu, F. Identification of a novel PAX6 mutation in a Chinese family with aniridia. BMC Ophthalmol. 2019, 19, 10. [Google Scholar] [CrossRef]
- Grant, M.K.; Bobilev, A.M.; Branch, A.; Lauderdale, J.D. Structural and functional consequences of PAX6 mutations in the brain: Implications for aniridia. Brain Res. 2021, 1756, 147283. [Google Scholar] [CrossRef] [PubMed]
- Tzoulaki, I.; White, I.M.S.; Hanson, I.M. PAX6 mutations: Genotype-phenotype correlations. BMC Genet. 2005, 6, 27. [Google Scholar] [CrossRef] [Green Version]
- Grønskov, K.; Olsen, J.H.; Sand, A.; Pedersen, W.; Carlsen, N.; Jylling, A.; Lyngbye, T.; Brøndum-Nielsen, K.; Rosenberg, T. Population-based risk estimates of Wilms tumor in sporadic aniridia. Human Genet. 2014, 109, 11–18. [Google Scholar] [CrossRef]
- Tian, W.; Zhu, X.R.; Qiao, C.Y.; Ma, Y.N.; Yang, F.Y.; Zhou, Z.; Feng, J.P.; Sun, R.; Xie, R.R.; Lu, J.; et al. Heterozygous PAX6 mutations may lead to hyper-proinsulinemia and glucose intolerance: A case-control study in families with congenital aniridia. Diabet. Med. 2020, 38, e14456. [Google Scholar] [CrossRef] [PubMed]
- Vlachopapadopoulou, E.A.; Dikaiakou, E.; Fotiadou, A.; Sifianou, P.; Tatsi, E.B.; Sertedaki, A.; Kanaka-Gantenbein, C.; Michalacos, S. Detection of hepatocyte nuclear factor 4A(HNF4A) gene variant as the cause for congenital hyperinsulinism leads to revision of the diagnosis of the mother. J. Pediatr. Endocrinol. Metab. 2020. [Google Scholar] [CrossRef]
- Ahlqvist, E.; Turrini, F.; Lang, S.T.; Taneera, J.; Zhou, Y.; Almgren, P.; Hansson, O.; Isomaa, B.; Tuomi, T.; Eriksson, K.; et al. A common variant upstream of the PAX6 gene influences islet function in man. Diabetologia 2012, 55, 94–104. [Google Scholar] [CrossRef] [Green Version]
- Hart, A.W.; Mella, S.; Mendrychowski, J.; van Heyningen, V.; Kleinjan, D.A. The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas. PLoS ONE 2013, 8, e54173. [Google Scholar] [CrossRef] [Green Version]
- Zheng, X.R.; Pan, X.; Zhang, J.; Cao, X. Hyperinsulinemia-induced PAX6 expression promotes endometrial epithelial cell proliferation via negatively modulating p27 signaling. Biomed. Pharmacother. 2018, 97, 802–808. [Google Scholar] [CrossRef] [PubMed]
- Nishi, M.; Sasahara, M.; Shono, T.; Saika, S.; Yamamoto, Y.; Ohkawa, K.; Furuta, H.; Nakao, T.; Sasaki, H.; Nanjo, K. A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia. Diabet. Med. 2005, 22, 641–644. [Google Scholar] [CrossRef] [PubMed]
- Motoda, S.; Fujita, S.; Kozawa, J.; Kimura, T.; Fukui, K.; Ikuno, Y.; Imagawa, A.; Iwahashi, H.; Shimomura, I. Case of a novel PAX6 mutation with aniridia and insulin-dependent diabetes mellitus. J. Diabetes Investig. 2019, 10, 552–553. [Google Scholar] [CrossRef]
- Shimo, N.; Yasuda, T.; Kitamura, T.; Matsushita, K.; Osawa, S.; Yamamoto, Y.; Kozawa, J.; Otsuki, M.; Funahashi, T.; Imagawa, A.; et al. Aniridia with a Heterozygous PAX6 Mutation in which the Pituitary Function was Partially Impaired. Intern. Med. 2014, 53, 39–42. [Google Scholar] [CrossRef] [Green Version]
- Brar, P.C.; Heksch, R.; Cossen, K.; De Leon, D.D.; Kamboj, M.K.; Marks, S.D.; Marshall, B.A.; Miller, R.; Page, L.; Stanley, T.; et al. Management and Appropriate Use of Diazoxide in Infants and Children with Hyperinsulinism. J. Clin. Endocrinol. Metab. 2020, 105. [Google Scholar] [CrossRef]
- Kizu, R.; Nishimura, K.; Sato, R.; Kosaki, K.; Tanaka, T.; Tanigawara, Y.; Hasegawa, T. Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia. Horm. Res. Paediatr. 2017, 88, 316–323. [Google Scholar] [CrossRef] [PubMed]
- Demirbilek, H.; Hussain, K. Congenital Hyperinsulinism: Diagnosis and Treatment Update. J. Clin. Res. Pediatr. Endocrinol. 2017, 9, 69–87. [Google Scholar] [CrossRef] [PubMed]
Parameters (Units) (Reference Range) | Age | ||
---|---|---|---|
5 Months | 39 Months | 60 Months | |
Glucose (mg/dL) (50.0–100.0) | 25.0 | 38.0 | 156.0 |
Insulin (μU/mL) (hypoglycemic: <2.5; fasting: 1.0–30.0) | 14.1 | 17.3 | 3.1 |
C-peptide (ng/mL) (1.1–3.3) | 2.4 | 2.1 | 0.7 |
βOHB (μmol/L) (28.0–128.0) | 24.1 | 27.2 | 30.8 |
HbA1c (%)(4.4–6.0) | 4.0 | 4.6 | 6.1 |
FFA (μEq/L) (130.0–770.0) | 193.0 | 181.6 | 161.0 |
Ammonia (μg/dL) (20.0–80.0) | 72.0 | 80.6 | 51.0 |
Cortisol (μg/dL) (9.4–26.1) | 8.6 | 12.1 | 8.8 |
pH (7.3–7.4) | 7.4 | 7.4 | 7.3 |
HCO3− (mmol/L) (23.0–30.0) | 25.4 | 18.4 | 25.3 |
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Kim, J.-M.; Kim, S.-K.; Kim, S.-H.; Cho, W.-K.; Cho, K.-S.; Jung, M.-H.; Suh, B.-K.; Ahn, M.-B. Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation. Medicina 2021, 57, 582. https://doi.org/10.3390/medicina57060582
Kim J-M, Kim S-K, Kim S-H, Cho W-K, Cho K-S, Jung M-H, Suh B-K, Ahn M-B. Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation. Medicina. 2021; 57(6):582. https://doi.org/10.3390/medicina57060582
Chicago/Turabian StyleKim, Jee-Min, Seul-Ki Kim, Shin-Hee Kim, Won-Kyoung Cho, Kyoung-Soon Cho, Min-Ho Jung, Byung-Kyu Suh, and Moon-Bae Ahn. 2021. "Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation" Medicina 57, no. 6: 582. https://doi.org/10.3390/medicina57060582