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Neonatal Diabetes DNA Sequencing Panel

Neonatal diabetes mellitus (NDM) is a defect of insulin production characterized by the onset of hyperglycemia in the first six months of life. Clinical features include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. It is a rare condition occurring in one of 100,000 to 500,000 live births. About half of NDM cases are classified as transient neonatal diabetes mellitus (TNDM), in which the condition disappears during infancy but can reappear later in life. The remaining cases are life-long and are called permanent neonatal diabetes mellitus (PNDM). Management may be tailored depending on the specific mutations. For example, those with KCNJ11 and ABCC8 mutations can be successfully treated with oral sulfonylureas instead of insulin.

The NDM panel includes DNA sequencing of the four most common genes:

KCNJ11 Approximately 30% of PNDM is attributed to activating mutations of KCNJ11, the gene encoding the protein Kir6.2 which is one of the two components of the beta-cell plasma membrane ATP-dependent potassium channel. KCNJ11 mutations are also found to cause TNDM. Most patients with mutations in KCNJ11 have isolated diabetes, but 20% have DEND syndrome, which is associated with neurologic features such as generalized epilepsy and developmental delay.

ABCC8 Approximately 19% of PNDM is attributed to activating mutations of ABCC8, the gene encoding the protein SUR-1, the second of the two components of the beta-cell plasma membrane ATP-dependent potassium channel. ABCC8 mutations are also found to cause TNDM.

INS Approximately 20% of PNDM is attributed to mutations in INS, the gene encoding insulin.

GCK Rarely, PNDM is attributed to inactivating mutations of GCK, the gene encoding glucokinase (hexokinase IV). Carrier parents have mild diabetes mellitus or glucose intolerance (GCK-MODY).

Testing of these 4 genes can be performed simultaneously, sequentially or individually.

Suggested testing algorithm based on age at presentation:
< 6 months of age at diagnosis: KCNJ11, INS, ABCC8, GCK.
6-12 months at diagnosis: KCNJ11, INS.
Infants with hyperinsulinism: GCK, KCNJ11, ABCC8.

Test Name: Neonatal Diabetes Sequencing Panel
Test Code:
NEO DIAB
Test Description:
Polymerase Chain Reaction (PCR) followed by sequence analysis of the entire coding region of each gene
Synonyms:
KCNJ11, INS, ABCC8, GCK, Kir6.2, SUR-1, hyperinsulinism
Indication:
Testing some or all of these genes is appropriate for:
1. infants with persistent hyperglycemia +/- history of intrauterine growth retardation, osmotic polyuria, severe hydration and failure to thrive.
2. older individuals with history of the above symptoms
3. infants with hyperinsulinism
Related Tests:
Clinical Links: Permanent Neonatal Diabetes Mellitus Gene Review
DiabetesGenes.org
Availability:
Mon - Fri
Turnaround Time:
2-4 weeks
Methodology:
PCR followed by sequencing
Reference Range:
Interpretive report will be provided
Requisition:
Consent Form:
Sample Requirements: Type
Whole blood: 6-10 mL in EDTA (purple top) or ACD (yellow top).
DNA: 5 micrograms extracted DNA.

Processing
Do not spin. Refrigerate blood samples which will not be immediately shipped.

Shipping
Room temperature via overnight shipping.
Samples Received:
Monday - Friday 8am - 5pm PST
Special Considerations:
Cost:
Please e-mail Lab Client Services (labclientservices@seattlechildrens.org) or call at 206-987-2617 with any billing questions
CPT Code:
Please e-mail Lab Client Services (labclientservices@seattlechildrens.org) or call at 206-987-2617 with any billing questions