<unk>  Mellitus (NDM) Transient<unk>  Mellitus (TNDM) TNDM occurs within the first several days to weeks of an infant's life. Intrauterine growth restriction (IUGR) is commonly seen in affected individuals and defined as poor growth of an unborn baby while in his or her mother's womb. In comparison, of PNDM, the insulin dose requirement of TNDM is often lower. TNDM resolves on its own at an average age of twelve weeks. Although, individuals will relapse in 50% of cases (usually during childhood or young adulthood). The parts of the body that are mostly affected are the pancreas, central nervous system and various tissues of the body. An average of 70% of TNDM is caused by defects initiating over-expression of the father genes in the imprinted region (genes whose expression is dependent on the parent that contributed them) of chromosome 6q24 (Chromosome meaning a string-like structure made of nucleic acid and protein that carries genetic material). There are three mechanism that can cause 6q24-related TNDM, which includes the father's DNA being defected by uniparental isodisomy (UPD) on chromosome 6 and inherited duplication of 6q24 (inherited duplication is a small chromosomal change in which a very little amount of genetic material is copied in chromosome 6). The last possible cause of TNDM, the mother's genes are affected by DNA methylation (DNA methylation is the process in which methyl groups or CH3- are added to the DNA molecule. When a methyl group is located on a promoter, it stops gene transcription). In previous research, it has been observed the involvement of an imprinted gene within TNDM, is only expressed by the father's genetic material or chromosome, resulting in an increased expression of the imprinted gene by UPD or inherited duplication that leads to the onset of<unk> . Numerous defects within the genome can lead to over-expression of the father's defected genes in the chromosome 6q24 region and result in TNDM. However, there are two genes in this region that can be associated with TNDM: ZAC and HYMAI Genes ZAC is a zinc-finger protein that controls apoptosis (programmed cell death) and cell cycle arrest (cell division and duplication of DNA stops when the cell detects cell damage or defects) in PLAG1 (pleomorphic adenoma gene-like 1). PLAG1 is a transcription regulator of the type 1 receptor for pituitary adenylated cyclase-activating polypeptide (is a polypeptide that activates adenylate cyclase and increases the cyclic adenosine monophosphate or cAMP. cAMP is a second messenger that is used for neighboring cells to perform signal transduction in targeted cells), which is important for insulin secretion regulation. The function of the HYMAI (hydatiform mole-associated and imprinted transcript) is unknown. Second, chromosome 6q24-TNDM is caused by over-expression of imprinted genes at 6q24 (PLAGL1 ZAC and HYMAI). It was discovered that a differentially methylated region (DMR) is present within the shared promoter of these genes. Generally the expression of the mother's alleles of PLAGL1 and HYMAI are blocked or not expressed by DMR methylation and only the father's alleles of PLAG1 and HYMA1 are expressed. The previously listed genetic mechanisms result in twice the normal amount of these two genes and cause chromosome 6q24 TNDM. ZFP57 Gene Third, mother's hypomethylation defects (a genetic defect that stops the allele from getting a methyl group, which would inhibit transcription) can occur from an isolated genomic imprinting or occur as a defect called, "hypomethylation imprinted loci" (HIL). HIL is defined as the loss of a methyl group in the 5-methylcytosine nucleotide at a fixed position on a chromosome. Homozygous ( having two of the same alleles) or heterozygous (defined as having one each of two different alleles) ZFP57 pathogenic variant make up almost half of TNDM-HIL, but the other causes of HIL are unknown. Moreover, half of TNDM patients that contain chromosome 6q24-related TNDM experiencing re-occurrence of<unk>  during their childhood or young adulthood. The onset of insulin resistance and increased insulin requirements are associated with puberty and pregnancy initiating the relapse of<unk> . In the event of remission, individuals do not show symptoms or impairment Beta-cell function in the fasting state. Insulin secretory response to intravenous glucose loading might be abnormal in those destined to have a relapse of<unk> . TNDM caused by 6q24 genomic defects are always associated with IGUR. Other contributing factors are umbilical hernia and enlarged tongue, which are present in 9 and 30% of patients with chromosome 6q24 related TNDM. KCNJ11 and ABCC8 Genes In addition, TNDM initiated by the genes, KCNJ11 or ABCC8 mutations are similar to mutations in chromosome 6q24-related to TNDM. Normally, the birth weight in infants are lower in chromosome 6q24 TNDM patients and<unk>  is initiated at an earlier age (similar to readmission). There may be an overlap between chromosome 6q24 and KCNJ11 and ABCC8-related TNDM, making genetic diagnosis necessary for treatment. INS Gene Recessive mutations in the INS gene encoding insulin were discovered to trigger both PNDM and TNDM.<unk>  occurs because there is a decrease insulin biosynthesis as a result of homozygous mutations. Common phenotype is decreased birth weight and average age of diagnosis is one week. Previous studies show relapse of<unk>  occurred at an average age of 26 weeks. Permanent<unk>  Mellitus (PNDM) PNDM is associated with mutations in the Beta-cell ATP sensitive potassium channel (KATP) initiated by heterozygous leading to mutations in KCNJ11 and ABCC8, which is a result of 31% and 10% of PNDM cases (results based on Exeter experiment series). Twelve percent of mutations in the insulin gene leads to PNDM. KCNJ11 and ABCC8 Genes association with Beta-cell ATP Sensitive Potassium Channel KCNJ11 encodes Kir6.2 (a protein coding gene in the potassium channel) and ABCC8 encodes the gene, SUR1 (the type 1 subunit of the sulfonylurea receptor), a member of the ATP-binding cassette transporter family, the two components of the KATP channel. This channel links glucose metabolism to insulin secretion by closing in response to ATP. Blood glucose storage into Beta-cells lead to glycolysis and cause ATP generation. The elevated ATP/ adenosine diphosphate ratio causes closure of the KATP channel, and inhibit potassium efflux (a lot of potassium flows out of this channel), that leads to depolarization of the Beta-cell membrane. Depolarization is the loss of the difference in charge between the inner and outer parts of the plasma membrane of a muscle. This occurs because of change in permeability and migration of sodium ions inside the cell. The voltage gated channels then open, allowing calcium (Ca+) to flow inside the channel and cause exocytosis (active transport that moves molecules out of a cell by ejecting them in an energy using process) of insulin-containing granules from the Beta-cells. Activation of defects in KCNJ11 or ABCC8 seems to make the KATP channel less sensitive to ATP, leaving more channels in an open state after high levels of glucose occurs. Resulting in the failure of insulin response to high blood glucose and leading to NDM.
Neonatal diabetes
Transient neonatal diabetes
Neonatal hypoglycemia
Permanent neonatal diabetes
Transient hyperammonemia of the newborn
Shaken baby syndrome
Hemolytic disease of the newborn
Hemolytic disease of the newborn 