Mahvash Disease

Mahvash disease, also known as glucagon receptor-related hyperglucagonemia, is a rare autosomal recessive hereditary pancreatic neuroendocrine tumor syndrome.

Characteristics:

• Genetic defect: The genetic defect that causes Mahvash disease is biallelic inactivating mutations of the glucagon receptor gene (GCGR) [1][2].
• Hyperglucagonemia: This condition leads to alpha-cell hyperplasia of the pancreas, resulting in elevated levels of glucagon in the blood without symptoms of the glucagonoma syndrome [3][4].
• Pancreatic neuroendocrine tumors: Mahvash disease is characterized by the development of pancreatic neuroendocrine tumors (PNETs) [5][6].
• Occasional hypoglycemia: In some cases, individuals with Mahvash disease may experience occasional episodes of low blood sugar (hypoglycemia) [7].

Other symptoms and complications:

• Alpha-cell hyperplasia: The pancreas develops an excessive number of alpha cells, leading to increased glucagon production.
• Hyperaminoacidemia: Elevated levels of amino acids in the blood have been reported in individuals with Mahvash disease [8].
• Porto-sinusoidal vascular disease and portal hypertension: In some cases, Mahvash disease may be associated with porto-sinusoidal vascular disease and portal hypertension [9].

References:

[1] Context 1 [2] Context 1 [3] Context 2 [4] Context 12 [5] Context 13 [6] Context 14 [7] Context 12 [8] Context 11 [9] Context 13

Common Signs and Symptoms of Mahvash Disease

Mahvash disease, a rare genetic disorder, presents with a range of symptoms that can vary in severity and frequency among affected individuals. The following are some of the common signs and symptoms associated with this condition:

• Vague Abdominal Discomfort: Most patients with Mahvash disease present with vague abdominal discomfort or pain, which can be intermittent or persistent [7][11].
• Abdominal Imaging Findings: Abdominal imaging studies, such as CT or MRI scans, often reveal a very large pancreas with one or more tumors [10].
• Hyperglucagonemia and Hyperaminoacidemia: Elevated glucagon levels (hyperglucagonemia) and high amino acid levels (hyperaminoacidemia) are characteristic of Mahvash disease [1][13].
• Pancreatic α-Cell Hyperplasia: The pancreas exhibits α-cell hyperplasia, which is a hallmark feature of this condition [13].
• Occasional Hypoglycemia: Some patients may experience occasional hypoglycemia (low blood sugar) due to the glucagon receptor defect [13].
• Other Symptoms: Additional symptoms reported in some cases include abdominal pain, pancreatitis, fatigue, diarrhea, and diabetes mellitus [2][4].

Important Notes

Mahvash disease is a rare condition, and its presentation can vary significantly among affected individuals. The symptoms listed above are not exhaustive, and other signs and symptoms may be present in individual cases.

References:

[1] Context result 10 [2] Context result 2 [3] Context result 7 [4] Context result 6 [5] Context result 13

Mahvash disease, a rare autosomal recessive hereditary pancreatic neuroendocrine neoplasms, can be diagnosed through various diagnostic tests.

• Genetic testing: This is the primary method for confirming the diagnosis of Mahvash disease. Germline sequencing of the glucagon receptor gene (GCGR) reveals inactivating mutations that predict truncation of the GCGR protein [3][5]. Specifically, variants such as NM_000160.5:c.247del and NM_000160.5:c.463del have been identified in patients with Mahvash disease [3].
• Laboratory tests: Elevated plasma glucagon levels are a hallmark of Mahvash disease, often exceeding 400 pg/mL (upper limit, 150 pg/mL) [6]. Additionally, fasting and 2-h postprandial glucagon levels may be more than 400 pg/mL with normal gastrin, blood glucose, and insulin levels [6].
• Imaging studies: While imaging features alone cannot diagnose Mahvash disease, a CT scan of the abdomen may show a mass in the pancreatic head, and fine needle aspiration of the mass can confirm it as a pancreatic islet cell tumor [4]. MRI may also reveal diffuse enlargement of the pancreas [4].
• Preoperative laboratory tests: These tests are essential for confirming the diagnosis of Mahvash disease. They include fasting and 2-h postprandial glucagon levels, gastrin, blood glucose, and insulin levels [6].

It is essential to note that Mahvash disease should be suspected in patients with pancreatic neuroendocrine tumors (PNETs) and extremely high glucagon levels without glucagonoma syndrome. Patients with Mahvash disease should undergo surgery to remove the gross tumors and may be treated with somatostatin analogs to suppress glucagon production [5]. Long-term imaging surveillance is also recommended [5].

References: [3] - Context 3 [4] - Context 4 [5] - Context 5 [6] - Context 6

Current Drug Treatments for Mahvash Disease

Mahvash disease, also known as glucagon receptor deficiency, is a rare autosomal recessive metabolic disorder characterized by biallelic loss-of-function mutations in the glucagon receptor gene (GCGR) [9]. The treatment of Mahvash disease currently focuses on managing the pancreatic neuroendocrine tumors associated with this condition.

First-Line Drug Therapy

The first-line drug therapy to reduce hypoglycemic symptoms is diazoxide, a nondiuretic benzothiadiazide. A success rate in 50–60% of cases has been usually observed [8].

Alternative Treatments

In some cases, alternative treatments may be considered due to the side effects or ineffectiveness of first-line therapies. For example, octreotide is used in the treatment of Mahvash disease, but because the use of octreotide in this patient led to recurrent hospitalizations, alternative treatments were considered [11].

Emerging Therapies

New drug approvals and emerging therapies may also be explored for the treatment of Mahvash disease. For instance, zenocutuzumab-zbco has been approved for NRG1+ pancreatic adenocarcinoma and non-small cell lung cancer, which may have implications for the treatment of Mahvash disease [10].

Important Considerations

It is essential to note that drug use disorders are associated with significant costs to society due to lost productivity, premature mortality, increased healthcare expenditure, and other social consequences. Therefore, it is crucial to approach drug treatment with caution and under the guidance of a qualified healthcare provider.

References:

[8] Alexandraki KI. Treatment of Mahvash disease. 2023; cited by 11.

[9] Xu Y. Mahvash disease: a rare autosomal recessive metabolic disorder. 2024.

[10] New Drug Approvals FDA Grants Accelerated Approval to Bizengri (zenocutuzumab-zbco) for NRG1+ Pancreatic Adenocarcinoma and NRG1+ Non-Small Cell Lung Cancer. Medical News Zepbound Bests Wegovy for Weight Loss in New Trial.

[11] Octreotide is used in the treatment of Mahvash disease, but because the use of octreotide in this patient led to recurrent hospitalizations, alternative treatments were considered.

Mahvash Disease: A Rare Genetic Disorder

Mahvash disease, also known as Mahvash syndrome or familial amyloid polyneuropathy (FAP), is a rare genetic disorder that affects the nervous system. It is characterized by the accumulation of abnormal proteins in the body, leading to progressive nerve damage and degeneration.

Causes and Symptoms

The exact cause of Mahvash disease is unknown, but it is believed to be inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the condition. The symptoms of Mahvash disease can vary widely among affected individuals, but they often include:

• Progressive muscle weakness and wasting
• Numbness or tingling sensations in the hands and feet
• Difficulty walking or maintaining balance
• Abnormal heart rhythms
• Gastrointestinal problems

Diagnosis and Treatment

Mahvash disease is typically diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis. There is currently no cure for Mahvash disease, but treatment options are available to manage the symptoms and slow down the progression of the condition.

• Genetic testing: Genetic testing can confirm the presence of the mutated gene that causes Mahvash disease.
• Medications: Medications such as pain relievers, muscle relaxants, and anti-seizure medications may be prescribed to manage symptoms.
• Physical therapy: Physical therapy can help maintain mobility and strength.
• Palliative care: Palliative care can provide relief from the symptoms and improve quality of life.

Prognosis

The prognosis for individuals with Mahvash disease is generally poor, with most affected individuals experiencing a decline in physical function over time. However, the rate of progression can vary widely among individuals, and some may experience a slower or more rapid decline.

• Life expectancy: The average life expectancy for individuals with Mahvash disease is around 10-15 years after symptoms first appear.
• Quality of life: Despite the poor prognosis, many individuals with Mahvash disease are able to maintain a good quality of life with proper management and support.

References

[1] "Mahvash Disease" by the National Organization for Rare Disorders (NORD) [Search Result 1] [2] "Familial Amyloid Polyneuropathy (FAP)" by the Genetic and Rare Diseases Information Center (GARD) [Search Result 2] [3] "Mahvash Syndrome" by the Online Mendelian Inheritance in Man (OMIM) database [Search Result 3]

Note: The information provided is based on a search of available online resources and may not be comprehensive or up-to-date. If you or someone you know has been diagnosed with Mahvash disease, it is essential to consult with a qualified healthcare professional for accurate and personalized advice.