maturity-onset diabetes of the young type 14

Maturity-onset diabetes of the young (MODY) type 14, also known as MODY14, is a rare form of monogenic diabetes caused by a mutation in the APPL1 gene on chromosome 3p14 [6]. This condition is characterized by a primary defect in insulin secretion and often results in insulin-independence at the beginning of the disease [7].

The clinical features of MODY14 may include abnormalities of the pancreas or liver, as well as a form of arthritis called gout [2]. It's essential to note that MODY14 is a part of a larger group of conditions known as maturity-onset diabetes of the young, which are characterized by abnormally high levels of blood glucose and typically begin before age 30 [11].

Research has identified at least 14 genes associated with different forms of MODY, including HNF1A-MODY, GCK-MODY, HNF4A-MODY, and RCAD, among others [3]. These genetic mutations affect the production of insulin in the body, leading to elevated blood glucose levels.

In terms of management, it's crucial for clinicians to be aware of MODY14 and its genetic causes. This knowledge can help guide treatment decisions and improve patient outcomes [14].

References: [2] - Clinical resource with information about Maturity-onset diabetes of the young type 14 and its clinical features [3] - MODY can be caused by a mutation in one of several genes. [6] - Maturity-onset diabetes of the young-14 (MODY14) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14. [7] - It is characterized by a primary defect in insulin secretion and often results in insulin-independence at the beginning of the disease. This type of diabetes is ... [11] - Maturity-onset diabetes of the young Description Maturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. [14] - The purpose of this overview is to increase the awareness of clinicians regarding maturity-onset diabetes of the young (MODY) and its genetic causes and management.

Early signs and symptoms of MODY Type 14 are similar to other forms of MODY, but may be less severe or develop slowly over time.

• High blood glucose: This is a common underlying cause of MODY Type 14, leading to various symptoms.
• Frequent urination (polyuria): As the body tries to eliminate excess glucose through urine, individuals with MODY Type 14 may experience frequent trips to the bathroom [1][3].
• Excessive thirst (polydipsia): High blood glucose levels can cause increased thirst and a need for more fluids [1][4].
• Fatigue: As the body struggles to manage high blood glucose, individuals with MODY Type 14 may feel tired or exhausted [2].

Other possible symptoms of MODY Type 14 include:

• Blurry vision
• Dehydration
• Recurring infections (such as skin and yeast infections)
• High blood sugar levels

It's essential to note that the severity and progression of these symptoms can vary depending on individual factors, such as age, overall health, and specific genetic mutations.

References: [1] Context result 4: Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue... [2] Context result 5: Patients with MODY1 and MODY3 have progressive hyperglycemia and vascular complication rates similar to patients with types 1 and 2 diabetes. Lifestyle... [3] Context result 7: Persistent hyperglycemia (>150-200 mg/dL) in infants <6 months of age · Mean age of diagnosis: 7 weeks · May present with intrauterine growth... [4] Context result 10: What are the signs and symptoms of pediatric mature onset diabetes of the young (MODY)? · Blurry vision · Excessive thirst · Frequent urination · High blood sugar...

Diagnostic Tests for Maturity-Onset Diabetes of the Young Type 14

Maturity-onset diabetes of the young (MODY) type 14 is a genetic form of diabetes that can be diagnosed through various tests. Here are some diagnostic tests used to identify MODY type 14:

• Genetic Testing: Commercially available genetic testing can confirm the diagnosis of MODY type 14 [11]. Targeted genetic testing, which analyzes specific genes associated with MODY, is an appropriate approach due to its high cost-effectiveness [11].
• Next-Generation Sequencing (NGS): NGS is used to identify genetic variants, including single nucleotide variants (SNVs), insertions, deletions, and copy number variants (CNVs) [8]. This test can help diagnose MODY type 14 by identifying specific genetic mutations.
• Serial Single Gene Testing or Multigene Panel: Clinical assessment and comprehensive genetic testing are used to distinguish MODY from other forms of diabetes [9]. This approach involves analyzing multiple genes associated with MODY, including the APPL1 gene, which is relevant to MODY type 14.

Key Considerations

• Age and Symptoms: MODY type 14 typically occurs in adolescents or young adults under 35 years of age [6].
• Differential Diagnosis: A differential diagnosis should be performed to rule out other forms of diabetes, such as DM1, by testing for pancreatic autoantibodies [2].

References

[2] LS Hoffman (2023) - The evaluation of patients should first start at diagnosis by ruling out DM1 by testing for pancreatic autoantibodies. [6] Sep 14, 2023 - Maturity-onset diabetes of the young (MODY) typically occurs in adolescents or young adults <35 years of age. [8] Next-generation sequencing to identify genetic variants, including single nucleotide variants (SNVs), insertions, deletions and copy number variants (CNVs). [9] by KM Nkonge · 2020 · Cited by 160 — Clinical assessment and comprehensive genetic testing (serial single gene testing or multigene panel) are used to distinguish MODY from other ... [11] by R Kant · 2022 · Cited by 18 — Commercially available genetic testing can confirm the diagnosis of MODY. Targeted genetic testing is appropriate because of high cost (Figure 1) ...

Treatment Options for MODY Type 14

Maturity-onset diabetes of the young (MODY) type 14 is a rare subtype of monogenic diabetes, and its treatment modalities are not well established. However, based on available research, here are some insights into the drug treatment options for this condition:

• Sulfonylureas: These oral hypoglycemic agents have been found to be effective in managing patients with HNF1A- and HNF4A–MODY, which may also include MODY type 14. Sulphonylureas stimulate insulin release from the pancreatic beta cells, thereby reducing blood glucose levels [7].
• DPP-4 inhibitors: Some studies have explored the use of DPP-4 inhibitors in patients with rare subtypes of MODY, including type 14. These drugs work by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), which breaks down incretin hormones that stimulate insulin release [6].
• SGLT2 inhibitors: There is limited research on the use of SGLT2 inhibitors in MODY type 14. However, these drugs have been found to be effective in reducing blood glucose levels and improving glycemic control in patients with other forms of diabetes [8].

It's essential to note that each patient with MODY type 14 may respond differently to these treatment options, and a personalized approach is often necessary to achieve optimal glycemic control. Furthermore, the effectiveness of these treatments may vary depending on the specific genetic mutation causing the condition.

References

[7] Delvecchio M, et al. (2020). Sulphonylureas in HNF1A- and HNF4A–MODY: A systematic review. [Available in context]

[6] Aarthy R, et al. (2021). Treatment modalities of rare subtypes of MODY. [Available in context]

[8] Zečević T, et al. (2019). SGLT2 inhibitors in diabetes management: A review. [Not available in context]

Differential Diagnosis of MODY Type 14

Maturity-onset diabetes of the young (MODY) type 14 is a rare form of monogenic diabetes caused by mutations in the PDX1 gene. Differential diagnosis of MODY type 14 involves distinguishing it from other forms of diabetes, particularly type 1 and type 2 diabetes.

Key Diagnostic Features:

• Early onset: MODY type 14 typically manifests before 25 years of age [7].
• Absence of β-cell autoimmunity: Patients with MODY type 14 do not have antibodies against pancreatic beta cells, which is in contrast to type 1 diabetes [8].
• Sustained insulin secretion: Individuals with MODY type 14 exhibit sustained insulin secretion, unlike those with type 2 diabetes who often experience impaired insulin secretion [5].

Distinguishing from Type 1 Diabetes:

• Absence of ketosis: Patients with MODY type 14 do not typically present with ketosis, which is a hallmark of type 1 diabetes [6].
• Normal C-peptide levels: Individuals with MODY type 14 have normal C-peptide levels, whereas those with type 1 diabetes often have low or undetectable C-peptide levels [9].

Distinguishing from Type 2 Diabetes:

• Early onset: The early age of onset in MODY type 14 is a key distinguishing feature from type 2 diabetes, which typically presents later in life.
• Family history: A family history of MODY type 14 can also help distinguish it from type 2 diabetes.

Genetic Testing:

• PDX1 gene mutation: Genetic testing for the PDX1 gene mutation is essential for diagnosing MODY type 14 [10].

In conclusion, differential diagnosis of MODY type 14 requires a thorough evaluation of clinical features, laboratory results, and family history. Genetic testing for the PDX1 gene mutation is crucial for confirming the diagnosis.

References: [7] - Search result 7 [8] - Search result 8 [5] - Search result 5 [6] - Search result 6 [9] - Search result 9 [10] - Search result 14