Neonatal diabetes caused by disrupted pancreatic and β‐cell development

Franco, Elisa De

doi:10.1111/dme.14728

Cited by 11 publications

(6 citation statements)

References 49 publications

(61 reference statements)

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“…La DN (MIM: 600937) hace parte del grupo de diabetes monogénicas, caracterizadas por la mutación en un único gen, responsable de la enfermedad (6), se han descrito más de 30 mutaciones genéticas relacionadas con DN, responsables de más del 85 % de los casos (7). La variante patogénica altera la función de las células beta del páncreas, afecta la secreción de insulina y provoca hiperglicemia (8).…”

Section: Discussionunclassified

“…La variante patogénica altera la función de las células beta del páncreas, afecta la secreción de insulina y provoca hiperglicemia (8). La DN se clasifica en transitoria, permanente o sindrómica (7). La DN transitoria ocurre en el 45 a 50 % de los casos (1,7,9), se caracteriza por hiperglicemia, ausencia de cetoacidosis diabética y restricción del cre-cimiento en los primeros días o semanas de vida (9).…”

Section: Discussionunclassified

“…La DN se clasifica en transitoria, permanente o sindrómica (7). La DN transitoria ocurre en el 45 a 50 % de los casos (1,7,9), se caracteriza por hiperglicemia, ausencia de cetoacidosis diabética y restricción del cre-cimiento en los primeros días o semanas de vida (9). En la DN transitoria se presenta disminución progresiva en los requerimientos de insulina y se observa la remisión de la enfermedad de forma general antes de los 18 meses de vida (1,7), con un 50 % de riesgo de reaparición en la adolescencia o en el inicio de la vida adulta (2,6,7).…”

Section: Discussionunclassified

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Diabetes neonatal: reporte de caso y revisión de tema

Sánchez Pinzón,

Atencia Herrera,

Sánchez Tordecilla

et al. 2023

Pediatria.

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Antecedentes: La diabetes neonatal se define como hiperglicemia persistente que ocurre con mayor frecuencia antes de los seis meses de edad y su incidencia es de 1 caso por cada 90 000 a 160 000 nacimientos. La diabetes neonatal se asocia a variantes patogénicas en un único gen, causando hiperglicemia, restricción del crecimiento intrauterino, bajo peso al nacer, alteraciones en el neurodesarrollo y se clasifica en transitoria, permanente o sindrómica. Las insulinas son el tratamiento inicial; sin embargo, las sulfonilureas han demostrado ser eficaces para el control de la hiperglicemia ante etiología originada en los genes KCNJ11 y ABCC8. Las sulfonilureas mejoran la capacidad motora y el neurodesarrollo, principalmente si la enfermedad se relaciona con KCNJ11. Reporte de caso: Neonato de sexo masculino con diagnóstico de DN por hiperglicemia persistente a las tres semanas del nacimiento, en el que se confirmó la mutación del gen ABCC8. Se encuentra en seguimiento por un grupo multidisciplinar. El tratamiento se caracterizó por el uso de insulina glulisina, insulina glargina y la transición al manejo con sulfonilurea. Se ha logrado el control de la glicemia, sin compromiso en el neurodesarrollo y con un crecimiento satisfactorio en el seguimiento. Conclusiones: El presente reporte de caso describe el diagnóstico clínico y genético de la DN por mutación del gen ABCC8, donde se puede observar características clínicas propias de la enfermedad como restricción del crecimiento intrauterino, bajo peso al nacer, hiperglicemia que requiere tratamiento con insulinas, la confirmación diagnostica por medio de genética médica y el tratamiento acorde con la transición del uso de insulinas al manejo con sulfonilurea.

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Section: Discussionunclassified

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Diabetes neonatal: reporte de caso y revisión de tema

Sánchez Pinzón,

Atencia Herrera,

Sánchez Tordecilla

et al. 2023

Pediatria.

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“…A recent expert review on neonatal diabetes, stated that it is still unclear whether recessive MNX1 mutations cause isolated or syndromic PNDM or both, since only two cases have been reported and that it would be essential to look for more cases to define its clinical phenotype 18 . Here we report the third case, it had syndromic PNDM, with a DKA presentation at onset together with urogenital anomaly (hypospadias) and congenital umbilical hernia.…”

Section: Patient and Methodsmentioning

confidence: 99%

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

Aly

Franco

Flanagan

et al. 2022

J of Diabetes Invest

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The MNX1 gene encodes a homeobox transcription factor found to be important for pancreatic beta cell differentiation and development. Mutations of the MNX1 gene that cause permanent neonatal diabetes mellitus (PNDM) are rare and have been reported in only two cases. Both cases presented with hyperglycemia, with one case having isolated PNDM while the other had PNDM and multiple neurologic, skeletal, lung, and urologic congenital anomalies resulting in death in early infancy. We describe the genetic and clinical features of a preterm male infant with a homozygous [c.816C > A p.(Phe272Leu)] MNX1 mutation. Our proband is the first case to present in severe diabetic ketoacidosis (DKA), indicating severe insulin deficiency. Unlike the previously reported female case who had the same mutation and presented with isolated PNDM, our proband had hypospadias and congenital umbilical hernia and showed poor growth on follow up. Our case suggests that MNX1 mutations causing NDM can result in a range of extra‐pancreatic features and a variable phenotype, similar to other transcription factors causing NDM such as GATA6 and GATA4 mutations. We also cannot exclude the possibility of sex‐biased expression of MNX1 gene (which was recently reported for other monogenic/neonatal diabetes genes such as the NEUROD1 and HNF4A in humans) since the two male cases had associated multiple anomalies while the female case had isolated PNDM. Our report further defines the phenotype caused by recessive homozygous MNX1 mutations and explores potential new mechanisms regulating MNX1 gene expression which should be further explored.

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“…More than 30 genes have been associated with NDM so far ( 10 , 11 ). The underlying mechanisms involved in the development of NDM are pancreas malformation or abnormal function of the β cells responsible for insulin synthesis or secretion ( 3 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Case report: Better late than never, but sooner is better: switch from CSII to sulfonylureas in two patients with neonatal diabetes due to KCNJ11 variants

et al. 2023

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Neonatal diabetes mellitus (NDM) is a rare genetic disease characterized by severe hyperglycemia requiring insulin therapy with onset mostly within the first 6 months and rarely between 6-12 months of age. The disease can be classified into transient (TNDM) or permanent neonatal diabetes mellitus (PNDM), or it can be a component of a syndrome. The most frequent genetic causes are abnormalities of the 6q24 chromosomal region and mutations of the ABCC8 or KCNJ11 genes coding for the pancreatic beta cell’s potassium channel (KATP). After the acute phase, patients with ABCC8 or KCNJ11 mutations treated with insulin therapy can switch to hypoglycemic sulfonylureas (SU). These drugs close the KATP channel binding the SUR1 subunit of the potassium channel and restoring insulin secretion after a meal. The timing of this switch can be different and could affect long-term complications. We describe the different management and clinical outcome over the time of two male patients with NDM due to KCNJ11 pathogenetic variants. In both cases, continuous subcutaneous insulin infusion pumps (CSII) were used to switch therapy from insulin to SU, but at different times after the onset. The two patients kept adequate metabolic control after the introduction of glibenclamide; during the treatment, insulin secretion was evaluated with c-peptide, fructosamine, and glycated hemoglobin (HbA1c), which were within the normal range. In neonates or infants with diabetes mellitus, genetic testing is an indispensable diagnostic tool and KCNJ11 variants should be considered. A trial of oral glibenclamide must be considered, switching from insulin, the first line of NDM treatment. This therapy can improve neurological and neuropsychological outcomes, in particular in the case of earlier treatment initiation. A new modified protocol with glibenclamide administered several times daily according to continuous glucose monitoring profile indications, was used. Patients treated with glibenclamide maintain good metabolic control and prevent hypoglycemia, neurological damage, and apoptosis of beta cells during long‐term administration.

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Neonatal diabetes caused by disrupted pancreatic and β‐cell development

Cited by 11 publications

References 49 publications

Diabetes neonatal: reporte de caso y revisión de tema

Diabetes neonatal: reporte de caso y revisión de tema

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

Case report: Better late than never, but sooner is better: switch from CSII to sulfonylureas in two patients with neonatal diabetes due to KCNJ11 variants

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