maturity-onset diabetes of the young type 3

Maturity-onset diabetes of the young (MODY) type 3, also known as HNF1A-MODY, is a form of MODY caused by mutations in the hepatocyte nuclear factor-1-alpha gene (HNF1A; 142410) on chromosome 12q24. This genetic mutation affects the production of insulin in the body, leading to diabetes.

Characteristics of HNF1A-MODY:

• Early age of onset: Diabetes typically develops before the age of 25.
• Familial inheritance: MODY runs in families from one generation to the next.
• Non-insulin dependent: Unlike type 1 diabetes, MODY is not caused by an autoimmune response and does not require insulin therapy initially.

Causes and risk factors:

• Genetic mutation: HNF1A-MODY is caused by a heterozygous mutation in the HNF1A gene.
• Family history: Individuals with a family history of MODY are more likely to develop the condition.

Symptoms and diagnosis:

• Diabetes symptoms: Patients may experience typical diabetes symptoms such as increased thirst, urination, and fatigue.
• Genetic testing: Genetic testing can confirm the presence of the HNF1A mutation and diagnose HNF1A-MODY.

Treatment and management:

• Lifestyle modifications: Patients with MODY should follow a healthy diet and exercise routine to manage their blood sugar levels.
• Medications: In some cases, medications such as metformin may be prescribed to help control blood sugar levels.

References:

[3] Tattersall and Fajans coined the term mature onset diabetes of the young (MODY) in 1974.[1] [5] MODY 3 or HNF1A-MODY is a form of maturity-onset diabetes of the young. It is caused by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome ... [8] The 3 main features of MODY are: Diabetes often develops before the age of 25; Diabetes runs in families from one generation to the next; Diabetes may be ...

Maturity-onset diabetes of the young (MODY) type 3, also known as MODY3, is a rare form of inherited diabetes that affects the way the body uses and stores sugar from food. The signs and symptoms of MODY3 can develop gradually over time, similar to those experienced by people with type 2 diabetes.

Early Signs and Symptoms:

• Frequent urination (polyuria) due to high blood glucose levels
• Excessive thirst (polydipsia)
• Fatigue
• Blurred vision
• Weight loss
• Recurrent skin infections

These symptoms are caused by the body's inability to produce enough insulin, leading to high blood sugar levels. It's essential to note that some people with MODY3 may not experience any noticeable symptoms at all.

Clinical Presentation:

There are two general types of clinical presentation for MODY3:

• Some forms of MODY3 can cause significant hyperglycemia and the typical signs and symptoms of diabetes, such as those listed above.
• Others may present with milder symptoms or no symptoms at all.

It's crucial to consult a healthcare professional for an accurate diagnosis and treatment plan. They will assess your individual situation and provide guidance on managing MODY3.

References:

[8] Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. [10] Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections.

Maturity-onset diabetes of the young (MODY) type 3 is a form of monogenic diabetes caused by mutations in the GCK gene, which encodes the glucokinase enzyme. Diagnostic tests for MODY type 3 are crucial to differentiate it from other forms of diabetes.

• Sanger sequencing: This is considered the most reliable method for diagnosing MODY type 3 (70). It involves analyzing the DNA sequence of the GCK gene to identify any mutations that may be causing the disease.
• Genetic testing: Genetic testing can help identify the specific mutation in the GCK gene that is causing MODY type 3. This can be done through various methods, including Sanger sequencing and next-generation sequencing (NGS).
• Blood sugar tests: Blood sugar tests are used to diagnose diabetes in general. However, for MODY type 3, a diagnosis of diabetes may not always be accompanied by the typical symptoms or characteristics of other forms of diabetes.
• Family history: A family history of MODY type 3 can also be an important factor in diagnosing this condition.

It's worth noting that genetic testing is not always necessary for a diagnosis of MODY type 3, and a clinical diagnosis based on the patient's symptoms and medical history may be sufficient. However, genetic testing can provide valuable information for family members who may be at risk of developing the disease (8).

References:

• [3] Sanger sequencing is the most reliable method for MODY diagnosis (70).
• [6] Candidates for this test are patients with MODY.
• [8] A blood sugar test is the first step toward diagnosing MODY. If your results indicate you have diabetes, your doctor may order additional tests.
• [11] The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time.
• [13] It is estimated to be the underlying cause of diabetes in 1-2% of patients diagnosed with diabetes, but prevalence estimates will not be accurate until large population screening studies are performed.

Treatment Guidelines for MODY3

Maturity-onset diabetes of the young type 3 (MODY3) is a form of monogenic diabetes that can be effectively managed with drug treatment. The primary goal of treatment is to lower plasma glucose levels and prevent complications.

• Sulfonylureas: Long-acting sulphonylureas are considered the first-line treatment for MODY3 patients [13]. These medications stimulate insulin release from the pancreas, thereby lowering blood sugar levels. Examples include gliclazide and glimepiride.
• Additional Treatment Options: In some cases, additional treatment with other oral hypoglycemic agents may be necessary to achieve optimal glucose control [4]. This can include metformin or other sulfonylureas.
• SGLT2 Inhibitors: The addition of a SGLT2 inhibitor to a pre-existing regimen of supramaximal doses of gliclazide and metformin has been shown to be effective in achieving excellent glycaemic control [5].
• Insulin Therapy: In some cases, insulin therapy may be necessary for MODY3 patients who are unable to achieve adequate glucose control with oral medications alone.

Key Considerations

• Treatment guidelines differ from both Type 1 diabetes and Type 2 diabetes.
• Sulfonylureas are generally the first-line treatment for MODY3 patients.
• Additional treatment options, such as metformin or SGLT2 inhibitors, may be necessary to achieve optimal glucose control.

References

[4] Delvecchio M. (2020). Sulphonylureas in the management of HNF1A- and HNF4A–MODY. [Cited by 148]

[5] Sriravindrarajah A. (2021). Addition of a SGLT2 inhibitor to a pre-existing regimen of supramaximal doses of gliclazide and metformin in MODY3 patients. [Cited by 1]

[13] Tattersall R, Fajans S. (1974). Mature onset diabetes of the young (MODY). [Cited by 2]

Maturity-onset diabetes of the young (MODY) type 3, also known as HNF1A-MODY, is a rare form of monogenic diabetes caused by heterozygous mutations in the hepatocyte nuclear factor 1-α (HNF1A) gene. Differential diagnosis of MODY type 3 involves distinguishing it from other forms of diabetes, particularly type 1 and type 2 diabetes mellitus.

Key Features to Consider:

• Early Onset: MODY type 3 typically manifests before the age of 25.
• Non-Obese Status: Patients with MODY type 3 are often non-obese, which can help differentiate it from type 2 diabetes.
• Sustained Insulin Secretion: Individuals with MODY type 3 exhibit sustained insulin secretion, unlike those with type 1 diabetes who may have impaired insulin secretion.
• Absence of Autoantibodies: The absence of beta-cell autoantibodies can also help rule out type 1 diabetes.

Diagnostic Criteria:

The diagnostic criteria for MODY type 3 include:

• Onset age before 25 years
• Absence of beta pancreatic cells antibodies
• Sustained insulin secretion with or without the use of oral hypoglycemic agents
• Presence of HNF1A gene mutations

Differential Diagnosis:

To accurately diagnose MODY type 3, it is essential to rule out other forms of diabetes. This includes:

• Type 1 diabetes mellitus (DM1)
• Type 2 diabetes mellitus (DM2)
• Other rare forms of monogenic diabetes, such as GCK-MODY and HNF4A-MODY

Genetic Testing:

Diagnostic molecular genetic testing is available for the HNF1A gene mutations associated with MODY type 3. This can help confirm the diagnosis and provide a clear understanding of the underlying cause of the disease.

References:

• [3] by M Mendonça · 2024
• [6] by K Zečević · 2024
• [13] Diagnosis and management of maturity onset diabetes of the young (MODY) Gaya Thanabalasingham, 1 2 Katharine R Owen
• [15] Cystic renal disease is a prominent feature of HNF-1beta mutations. Further maturity-onset diabetes of the young genes remain to be identified. MODY is part of the differential diagnosis of diabetes presenting in the first to third decades of life. Diagnostic molecular genetic testing is available for the more common genes involved.