Monogenic Diabetes

Why is Monogenic Diabetes Diagnosis Critical?

Patients with monogenic diabetes are often misdiagnosed as Type 1 or Type 2 for years. According to the TCGS study and ISPAD 2022 guidelines, genetic identification leads to:

Targeted Treatment: Switching from insulin to sulfonylureas in HNF1A-MODY or KCNJ11-NDM patients.
Avoiding Unnecessary Treatment: GCK-MODY patients typically require no medication.
Cascade Screening: Identifying carriers in the family for early prevention.
Pharmacogenetics: Determining precise drug dosing based on the patient's hepatic metabolism profile.

Referral Criteria for Genetic Testing

Based on international guidelines, referral is strongly recommended if the patient meets the following criteria:

👶 Neonatal Diabetes (NDM)

Hyperglycemia diagnosed before 6 months of age.
Insulin requirement during infancy.
Suspected potassium channel mutations (KCNJ11, ABCC8) or INS gene.

🧬 Suspected MODY (Young Adults)

Diabetes diagnosis before age 35.
Normal BMI (< 25 kg/m²).
Negative Type 1 diabetes autoantibodies (GAD, IA-2, ZnT8).
Measurable C-Peptide >3 years after diagnosis.
Strong family history of diabetes (autosomal dominant pattern).

💊 Unexpected Treatment Response

Excellent glycemic control with very low-dose sulfonylureas.
Successful insulin discontinuation and switch to oral medication.
Extra-pancreatic symptoms present (renal cysts, hearing loss, lipodystrophy).

Sample Comprehensive Genetic & Pharmacogenetic Report

Our reports go beyond a simple result; they include clinical interpretation, therapeutic recommendations, and genetic counseling guidance.

Pathogenic Variant Found

Patient: Lilit Asatourian

Age: 3 yrs | Gender: Female

Genetic Finding:
Gene: HNF1A
Variant: NM_000545.8(HNF1A):c.1463_1473del (p.Pro488fs)
Note: Frameshift variant leading to truncated protein. Associated with MODY Type 3.

💡 Clinical Interpretation & Therapeutic Recommendation:

Confirmed Diagnosis: MODY Type 3 (HNF1A-MODY).
Drug Recommendation: Patients with HNF1A-MODY show high sensitivity to sulfonylureas. Switching from insulin to oral sulfonylureas is recommended under medical supervision.
Monitoring: Regular screening for microalbuminuria and retinopathy due to microvascular risk.
Family Counseling: Autosomal dominant inheritance. Cascade testing for parents and siblings is advised.

Physician Test Request Form

Please complete the clinical information below to ensure accurate variant interpretation.

1. Patient Information

Full Name:

National ID / Passport:

Date of Birth:

Gender:

Ethnicity:

2. Clinical Diagnosis & Lab Results

Age at Diabetes Diagnosis (Years):

BMI at Diagnosis:

HbA1c (%):

Fasting C-Peptide (ng/mL):

Fasting Insulin (µU/mL):

3. Type 1 Diabetes Autoantibodies

Antibody	Positive	Negative	Not Tested
GAD65
IA-2
ZnT8

4. Family History & Treatment

Diabetic Relatives (Check all that apply):
Father Mother Sister Brother

Diabetes in two consecutive generations?

Good response to sulfonylureas?

Current Treatment & Specific Symptoms:

This service is designed based on findings from the Tehran Cardiometabolic Genetic Study (TCGS) and ISPAD 2022 Clinical Practice Guidelines.