Neonatal diabetes is a group of metabolic pathologies which are shown by a hyperglycemia and a gipoinsulinemiya against the background of pancreas dysfunction. Clinical symptoms include a hyperglycemia, a polyuria, metabolic acidosis, a ketonemiya and a ketonuriya, dehydration, deficiency of body weight. Other manifestations depend on the main genetic pathology. Diagnostics is based on fizikalny survey of the child, laboratory blood tests and urine. Treatment depends on a form of neonatal diabetes. At tranzitorny option symptomatic correction of a hyperglycemia is carried out, at permanent diabetes lifelong insulin therapy is shown.
The Neonatal Diabetes (ND) is a set of heterogeneous pathologies in a neonatology and pediatrics of which the hyperglycemia and tranzitorny or permanent insufficiency of insulin against the background of dysfunction of β-cages of an endocrine part of a pancreas is characteristic. For the first time diabetes at the newborn described Kistel in 1852. Prevalence of this state makes 1:300-400 thousand newborns. The tranzitorny form develops in 55-60% of cases. Permanent NSD meets less often, and, as a rule, is a part of sindromologichesky pathologies. On average boys and girls are ill with an identical frequency, however some syndromes (for example, an IPEX syndrome) are more characteristic of a male. The type of inheritance of certain forms of neonatal diabetes also depends on concrete genetic anomaly and can be both autosomno-prepotent (defect of GK), and autosomno-recessive (KCNJ11).
Reasons of neonatal diabetes
The etiology of neonatal diabetes depends on its clinical form. Passing NSD results from defective development of β-cells of islets of Langerhans of a pancreas. Functionally unripe cages are incapable to provide proper response to increase in a glycemia. At the same time the basic level of insulin in plasma of blood can be normal. In most cases pathology develops sporadic. The hereditary tendency connected with anomalies of a long shoulder of the VI chromosome is also proved. Mutations of genes of ABCC8 and KCNJ11 can be the cause of tranzitorny neonatal diabetes, however defects of the same genes in some cases provoke development of a permanent form.
Persistiruyushchy neonatal diabetes is caused by anomalies of structure of β-cages, all gland or directly insulin because of what its absolute insufficiency develops. As a rule, it is hereditary defects of various genes. The most widespread options are heterozygotic mutations of genes of activation of ABCC8 and KCNJ11. Often the following anomalies causing development of NSD meet: IPF-1 – hypo - or an aplaziya of a pancreas, GK – lack of reaction to glucose level in blood, EIF2FK3 (Walcott-Rallison's syndrome) – insulin synthesis process violation, FOXRZ (IPEX syndrome) – autoimmune defeat of fabrics of gland. The permanent form can also be display of mitochondrial pathologies. In certain cases the enteroviral infection which mother had in the first trimester of pregnancy can provoke development of neonatal diabetes.
Classification and symptoms of neonatal diabetes
Neonatal diabetes has two main clinical forms:
- Passing or tranzitorny NSD. More widespread option. Irrespective of the carried-out treatment symptoms gradually disappear aged up to 3 months. Full remission occurs aged from 6 months till 1 year. A recurrence at adult age is possible.
- Persistiruyushchy or permanent NSD. Often enters into structure of sindromalny malformations. Demands lifelong insulin therapy.
Clinical displays of tranzitorny and permanent neonatal diabetes in the absence of other sindromalny violations are almost identical. At passing NSD the delay of pre-natal development is often observed – children are born with body weight much less norm (lower than 3 percentiles) for the term of a gestation. The general condition of the child at a tranzitorny form is broken slightly – the patient inactive, sluggish, appetite is lowered or kept. Comas are uncharacteristic. Even against the background of good nutrition the child slowly adds to body weight. A specific symptom of neonatal diabetes is the expressed polyuria and dehydration, is frequent – a pungent smell of acetone from a mouth.
All above-mentioned symptoms, but bigger intensity are characteristic of a permanent form of neonatal diabetes. Despite it, the delay of pre-natal development is expressed not so strongly. Other possible symptoms depend on whether NSD enters into structure of this or that syndrome. At development of an IPEX syndrome the hyperglycemia is combined by other endocrine and immune violations and a tseliaknegativny enteropatiya. Clinically it is shown by eczema, chronic diarrhea, an autoimmune tireoidit, hemolytic anemia. Walcott-Rallison's syndrome besides neonatal diabetes includes a renal failure, violations of intelligence, a gepatomegaliya and a spondiloepifizarny dysplasia.
Diagnosis of neonatal diabetes
Diagnosis of neonatal diabetes includes fizikalny survey of the newborn, laboratory and tool methods of a research. Collecting anamnestichesky data at mother, as a rule, allows to define expressiveness of already available manifestations – a polyuria, a slow increase to body weight. At objective inspection the general adinamiya of the child, dryness of integuments and other displays of dehydration comes to light. In most cases at children lag in physical development and deficiency of body weight is observed.
Laboratory analyses play the leading role in diagnosis of neonatal diabetes. At blood test the stable hyperglycemia more than 10-11 mmol/l, increase in level of ketone bodies over 3 mmol/l, rnmetabolichesky acidosis is defined. In the analysis of urine it is possible to find a glucosuria and a ketonuriya. When conducting test across Zimnitsky increase in a daily diuresis comes to light (polyuria) and increase in specific weight of urine. Tool diagnostics in the form of BRIDLES, a X-ray analysis of OBP, an ultrasonografiya is used for an exception of organic violations and definition of other displays of sindromalny pathologies. At an opportunity the kariotipirovaniye with identification of defective genes is carried out.
The differential diagnosis of neonatal diabetes is carried out with a hyperglycemia of newborns, a glikozuriya against the background of massive infusional therapy, pre-natal infections, inflammatory diseases of TsNS – meningitis and encephalitis, renal diabetes, infections of an intestinal path, a malabsorption syndrome, sharp surgical abdominal pathologies.
Treatment of neonatal diabetes
Therapeutic tactics at permanent and tranzitorny forms of neonatal diabetes significantly differs. Replaceable insulin therapy which is supplemented with high-calorific food is shown to children with persistiruyushchy NSD. The therapeutic scheme approaches individually for each child on the basis of sensitivity insulin and glucose level in blood. As a rule, apply insulin of both short, and long action. Depending on the present sindromalny pathology of neonatal diabetes the corresponding correction is carried out. For example, at a mutation of a gene of FOXRZ cytostatics are appointed, bone marrow transplantation is carried out, and at defect of KCNJ11 instead of insulin sulfanylurea medicines are used. Replaceable insulin therapy is shown throughout all life.
At patients with a tranzitorny form of neonatal diabetes insulin therapy is used only at high levels of a glycemia, an eksikoza, the expressed violation of the general state, deficiency of body weight and its slow set. For the first 6-12 months the need for antihyperglycemic medicines decreases, and then vanishes – there occurs full remission. Control over the level of glucose of blood and correction of doses of medicines depending on NSD loudspeakers can be carried out each 7 days or once a month at the endocrinologist and the pediatrician or the family doctor.
Forecast and prevention of neonatal diabetes
The forecast at a tranzitorny form of neonatal diabetes favorable. As a rule, aged from 6 months till 1 year there occurs full clinical remission. At a part of children violation of tolerance to glucose can be observed further. Also there is a risk of development of autoimmune diabetes at the age of 20-30 years. The forecast concerning recovery at a permanent form of neonatal diabetes adverse. Regardless of the present pathologies the child will be forced to accept insulin for life. The forecast for life at this NSD form doubtful. The outcome in many respects depends on existence of these or those genetic disorders. At an IPEX syndrome most of children die aged till 1 year of severe forms of sepsis.
Specific prevention of neonatal diabetes it is not developed. Nonspecific preventive measures include medico-genetic consultation of married couples with assessment of probability of the birth of the child with this pathology. At high risk of emergence of NSD at future child performing amniocentesis with the subsequent kariotipirovaniye is possible.