Neonatal diabetes exemplifies the interrelation of genetics and epigenetics
Childhood diabetes is grouped into several subtypes, depending on genetic patterns and their own etiological and pathophysiological mechanisms.Each form has a different management, as revealed in the XXII National Congress of the Spanish Diabetes Society, which has been held in Malaga.
In some cases, transient neonatal diabetes has shown that it is a disorder that exemplifies the interrelation between genetics and epigenetics in diabetes, according to specialists participating in the XXII National Congress of the Spanish Society of Diabetes, which has beenheld in Malaga.
"This will continue to study and cause a broader spectrum of clinical studies, since through neonatal hyperglycemia we can reach the much broader study of other subsequent problems," Juan P. López-Siguero, of the pediatric endocrinology service of the pediatric endocrinology of theMaternal-Infantil Hospital of Malaga.
Neonatal diabetes, where the child's weight is very important at birth for the prognosis, which takes place in the first 15 days of life, is not a unique entity but a heterogeneous group of alterations with different genetic pattern and different etiological and pathophysiological mechanisms.Therefore, childhood diabetes can be grouped into several main subtypes such as transient or permanent neonatal diabetes (DMNT and DMNP), type 1 diabetes (DM1), type 2 diabetes (DM2), MODY DIABETES, Mitochondrial Diabetes (DMMT), diabetes related to cystic fibrosis (DRFQ) or diabetes associated with syndromes such as Down and Turner.
The cause of the DMNP is not totally clarified.The DMNP association with cerebellar hypoplasia and Wolcott-rallison syndrome has been described, which suggests a autosomal recessive inheritance pattern.
"Children who suffer from this disease are very difficult to handle and need insulin therapy in small dose, since it has hyperglycemia after having hypoglycemia," said the Malaga doctor and added that "when the child has less than six months hyperglycemiaIt is treated with insulin and then we can focus on whether neonatal diabetes is transient or permanent
Frequency
Likewise, the frequency of neonatal diabetes at this time is one for every 400,000 or 500,000, but with epidemiological studies it has been lowered by half, one in 250,000 or 200,000, and continues to be a rare disease, characterized by genetic alterationsmonogenic.
In this way, "the most frequent genetic alteration, within which we know, is that of chromosome 6, located in particular in the 6Q24 position, which in all cases usually causes transient neonatal diabetes and that obeys a pattern of genetic imprint"López-Siguero explained.He has emphasized that "an alteration in duplication may occur or, although it is less frequent, during translation and methylation."
This refers to the loss of genetic imprint in the maternal allele, which causes an unbalanced duplication of the 6Q region of paternal origin, paternal isodisomy.
In addition, you have to focus on alterations in potassium subunits, Kir 6.2 and South1, which can occur both in the DMNT and DMNP;"Perhaps the permanent Kir 6.2 and the transient of Sur1 is more frequent."
As for genetic investigations, "they will change the possibility of the treatment of DMNP with sulfonylureas so as not to make that patient in insulin dependent," said the specialist."Glucocinase was subsequently introduced for patients who have a very early genetic presentation of diabetes; it should also be considered the insulin gene that is related right nowwith 10 or 12 percent of neonatal diabetes. "
Common features
The alteration in 6q24 is a three -phase disease;It corresponds to young children in gestational age who have a DMNT, who debut soon, in the first week of life, who do not have ketoacidosis, also refer soon and usually recurrence after puberty."The times are difficult, because the long-term monitoring has been irregularly, and will be in charge of the endocrinologists to monitor if there will be a subsequent diabetes," said López-Siguero and has insisted that "the most frequent cause is theAlterations of the South1, the potassium channels ".
Sometimes, diabetes related to Kir 6.2, which has neurological alterations."The alteration of the subunit of potassium Kir 6.2 with diabetes is fundamental and permanentThe endocrinologist.
On the other hand, DMNP dysplasia as a cause and associated with liver disease is the most frequent within neonatal diabetes with consanguinity."It is treatable with permanent sulfonylureas and the doses can cover from 0.1 milligrams per kilo every 12 hours to 0.2 milligrams per kilo a day; some cases in dend syndrome can reach a larger dose, although you have to monitor thelong -term effects ".
Children's control and management
The therapeutic attitude to be faced with a patient with a diagnosis of neonatal diabetes is, first, to treat him with insulin or insulin analogues such as subcutaneous insulin or the continuous pressure pump."They are complex treatment children, with two or three weeks of life, poorly nourished, dehydrated and who need to live doses difficult to administer, many times through a bomb," said Juan P. López-Siguero.
"There are few cases where a gene produces alteration of methylation, such as ZFP 57, which has been described more frequently in children who were born through in vitro fertilization with other genetic alterations; there are also other patients with methylation alterationsand that they do not have hyperglycemia which is not strange if it does not affect much at 6q24 ".
