What are the other Names for this Condition? (Also known as/Synonyms)

• 6q24-Related TNDB
• Chromosome 6-Associated Transient Diabetes Mellitus 
• Diabetes Mellitus, 6q24-Related Transient Neonatal

What is Transient Neonatal Diabetes Mellitus? (Definition/Background Information)

• Transient NeonatalDiabetes Mellitus(TNDB) is a type ofdiabetesthat appears within the first few weeks of life but is transient. The affected infants go intoremissionwithin a few months, with possible relapse to permanent diabetes in adolescence or adulthood
• Affected individuals have slow growth before birth followed byhyperglycemia, dehydration andfailure to thrivein infancy
• Approximately 70% of cases are caused by the over activity of certaingenesin a region of the long (q) arm ofchromosome 6called 6q24. These cases are referred to as6q24-related TNDB; most (but not all) of these cases are notinherited
• Other genetic causes includemutationsin theKCNJ11andABCC8genes, which usually causepermanent neonatal diabetes
• Treatment may include rehydration and intravenous insulin at the time of diagnosis, followed by subcutaneous insulin

(Source: Transient NeonatalDiabetes Mellitus; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Transient Neonatal Diabetes Mellitus? (Age and Sex Distribution)

• Transient NeonatalDiabetes Mellitus is a rare congenital disorder. The presentation of symptoms occurs at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Transient Neonatal Diabetes Mellitus? (Predisposing Factors)

• A positive family history may be an important risk factor, since Transient NeonatalDiabetes Mellitus can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Transient Neonatal Diabetes Mellitus? (Etiology)

• Approximately 70% of cases of Transient NeonatalDiabetes Mellitus are caused by the over activity of certaingenesin a region of the long (q) arm ofchromosome 6called 6q24 These cases are referred to as6q24-related TNDB; most (but not all) of these cases are notinherited
• Other genetic causes includemutationsin theKCNJ11andABCC8genes, which usually causepermanent neonatal diabetes

(Source: Transient NeonatalDiabetes Mellitus; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Heterozygous mutations in the KCNJ11 (11p15.1) and ABCC8 (11p15.1) genes account for 26% of cases. Homozygous or compound heterozygous ZFP57 (6p22.1) mutations have also been reported to cause TNDB
• Thus, TNDB can be inherited in an autosomal dominant or autosomal recessive manner, depending on the gene causing the disorder

(Source: Transient NeonatalDiabetes Mellitus; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Transient Neonatal Diabetes Mellitus?

The signs and symptoms of Transient NeonatalDiabetes Mellitus may differ in type and severity among affected babies, and include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of the pancreatic islet cells
• Dehydration
• Failure to thrive
• Glycosuria
• Hypovolemia
• Intrauterine growth retardation
• Weight loss

Frequently present symptoms in 30-79% of the cases:

• Bilateral ptosis
• Contractures of the joints of the lower limbs
• Downturned corners of mouth
• Intellectual disability
• Ketonuria
• Motor delay
• Prominent metopic ridge

Occasionally present symptoms in 5-29% of the cases:

• Abnormal heart morphology
• Apraxia
• Coma
• Generalized myoclonic seizures
• Generalized tonic-clonic seizures
• Hearing impairment
• Muscular hypotonia
• Neonatal onset
• Renal tubular dysfunction
• Steatorrhea

(Source: Transient NeonatalDiabetes Mellitus; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Transient Neonatal Diabetes Mellitus Diagnosed?

Transient NeonatalDiabetes Mellitus is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Transient Neonatal Diabetes Mellitus?

The complications of Transient Neonatal Diabetes Mellitus may include:

• Failure to gain age-appropriate weight 
• Relapse of diabetes mellitus
• Intellectual deficit, which can affect one’s quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Transient Neonatal Diabetes Mellitus Treated?

Early diagnosis and appropriate treatment are crucial for Transient Neonatal Diabetes Mellitus.

• Initial treatment mainly involves rehydration and intravenous insulin. Some infants however do not require insulin therapy 
• Insulin can rapidly be switched to the subcutaneous route or to continuous insulin pump therapy and discontinued once blood glucose levels have stabilized 
• During relapse of DM, which is poorly characterized, some patients can be treated with diet alone, but others require oral sulfonylurea or insulin

(Source: Transient NeonatalDiabetes Mellitus; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Transient Neonatal Diabetes Mellitus be Prevented?

Transient NeonatalDiabetes Mellitus may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Transient Neonatal Diabetes Mellitus? (Outcomes/Resolutions)

• Rapid catch-up growth is normally achieved through insulin treatment and normal height and weight is often reached by two years of age 
• Diabetes may recur in childhood, during puberty, or later in adulthood in about 85% of patients 
• The prognosis of Transient Neonatal Diabetes Mellitus is generally good, but is dependent on timely rehydration and adequate control of potential complications

(Source: Transient NeonatalDiabetes Mellitus; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Transient Neonatal Diabetes Mellitus:

Transient NeonatalDiabetes Mellitus is also known by the following acronyms: 

• TNDM1
• TNDM 
• DMTN

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/