Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India
Aim and Objectives: 1. To study the clinical outcome, growth and glycaemic control, 2. To study the frequency and type of genetic mutations. Methods: This is a retrospective study with a review of data of medical records from 2008 till date. Results: Twelve patients (six males) with neonatal diabete...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Indian Journal of Endocrinology and Metabolism |
| Subjects: | |
| Online Access: | http://www.ijem.in/article.asp?issn=2230-8210;year=2022;volume=26;issue=1;spage=79;epage=86;aulast=Korula |
| _version_ | 1818469028376608768 |
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| author | Sophy Korula Lavanya Ravichandran Praveen G Paul Jabasteen Johnson Aaron Chapla Sridhar Santhanam Anna Simon Sarah Mathai |
| author_facet | Sophy Korula Lavanya Ravichandran Praveen G Paul Jabasteen Johnson Aaron Chapla Sridhar Santhanam Anna Simon Sarah Mathai |
| author_sort | Sophy Korula |
| collection | DOAJ |
| description | Aim and Objectives: 1. To study the clinical outcome, growth and glycaemic control, 2. To study the frequency and type of genetic mutations. Methods: This is a retrospective study with a review of data of medical records from 2008 till date. Results: Twelve patients (six males) with neonatal diabetes mellitus (NDM) were identified. Median (interquartile range – (IQR)) age at diagnosis was 72 (31–95) days with a history of consanguinity in 75%. The median birth weight (range) was 2345 (900–3300) g. Follow-up data were available for eight patients with a median age at (IQR) follow-up of 3.3 (3–5.3) years. At follow-up, the mean annual HbA1c was 8.2% at a mean insulin dose of 1.1 U/kg/d. One patient with Wolcott-Rallison syndrome (WRS) and 21α-hydroxylase deficiency had poor growth and intellectual difficulty. The rest demonstrated satisfactory growth with an increase of mean weight centile from 2nd to 13th, height centile from 6.5th to 20th and normal neuro-cognitive development. Eleven patients underwent genetic testing with a molecular diagnosis in 54% (6/11): EIF2AK3 (n = 2) and one each in INS, PDX1, IL2RA and FOXP3. None had variants in ABCC8 or KCNJ11. One with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome underwent haematopoietic stem cell transplant (HSCT) and later succumbed. Conclusion: Our study demonstrates good clinical outcomes among NDM patients without immune dysfunction. Molecular diagnosis was attained only in around half of the patients (54%) with a great genetic heterogeneity. |
| first_indexed | 2024-04-13T21:18:41Z |
| format | Article |
| id | doaj.art-6499b13e5c4b49db806002a1aa7ab9f6 |
| institution | Directory Open Access Journal |
| issn | 2230-8210 |
| language | English |
| last_indexed | 2024-04-13T21:18:41Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Journal of Endocrinology and Metabolism |
| spelling | doaj.art-6499b13e5c4b49db806002a1aa7ab9f62022-12-22T02:29:35ZengWolters Kluwer Medknow PublicationsIndian Journal of Endocrinology and Metabolism2230-82102022-01-01261798610.4103/ijem.ijem_429_21Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South IndiaSophy KorulaLavanya RavichandranPraveen G PaulJabasteen JohnsonAaron ChaplaSridhar SanthanamAnna SimonSarah MathaiAim and Objectives: 1. To study the clinical outcome, growth and glycaemic control, 2. To study the frequency and type of genetic mutations. Methods: This is a retrospective study with a review of data of medical records from 2008 till date. Results: Twelve patients (six males) with neonatal diabetes mellitus (NDM) were identified. Median (interquartile range – (IQR)) age at diagnosis was 72 (31–95) days with a history of consanguinity in 75%. The median birth weight (range) was 2345 (900–3300) g. Follow-up data were available for eight patients with a median age at (IQR) follow-up of 3.3 (3–5.3) years. At follow-up, the mean annual HbA1c was 8.2% at a mean insulin dose of 1.1 U/kg/d. One patient with Wolcott-Rallison syndrome (WRS) and 21α-hydroxylase deficiency had poor growth and intellectual difficulty. The rest demonstrated satisfactory growth with an increase of mean weight centile from 2nd to 13th, height centile from 6.5th to 20th and normal neuro-cognitive development. Eleven patients underwent genetic testing with a molecular diagnosis in 54% (6/11): EIF2AK3 (n = 2) and one each in INS, PDX1, IL2RA and FOXP3. None had variants in ABCC8 or KCNJ11. One with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome underwent haematopoietic stem cell transplant (HSCT) and later succumbed. Conclusion: Our study demonstrates good clinical outcomes among NDM patients without immune dysfunction. Molecular diagnosis was attained only in around half of the patients (54%) with a great genetic heterogeneity.http://www.ijem.in/article.asp?issn=2230-8210;year=2022;volume=26;issue=1;spage=79;epage=86;aulast=Korulamonogenic diabetesneonatal diabetesndmwollcott-rallison syndromeipex syndromeinsulindiabetes management |
| spellingShingle | Sophy Korula Lavanya Ravichandran Praveen G Paul Jabasteen Johnson Aaron Chapla Sridhar Santhanam Anna Simon Sarah Mathai Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India Indian Journal of Endocrinology and Metabolism monogenic diabetes neonatal diabetes ndm wollcott-rallison syndrome ipex syndrome insulin diabetes management |
| title | Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India |
| title_full | Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India |
| title_fullStr | Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India |
| title_full_unstemmed | Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India |
| title_short | Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India |
| title_sort | genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus a single centre study from south india |
| topic | monogenic diabetes neonatal diabetes ndm wollcott-rallison syndrome ipex syndrome insulin diabetes management |
| url | http://www.ijem.in/article.asp?issn=2230-8210;year=2022;volume=26;issue=1;spage=79;epage=86;aulast=Korula |
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