hypermanganesemia with dystonia 2

Hypermanganesemia with Dystonia 2 (HMNDYT2) Description

Hypermanganesemia with dystonia 2 is an autosomal recessive neurodegenerative disorder characterized by the loss of motor milestones in the first years of life. As individuals affected by this condition progress, they develop rapidly progressive abnormal movements, including dystonia, spasticity, bulbar dysfunction, and other neurological symptoms.

Key Features:

• Loss of Motor Milestones: Affected individuals experience a delay or absence of normal motor development milestones in the first years of life.
• Rapidly Progressive Abnormal Movements: As the condition progresses, individuals develop dystonia (involuntary muscle contractions), spasticity (increased muscle tone), bulbar dysfunction (problems with swallowing and speech), and other abnormal movements.
• Neurodegenerative Disorder: Hypermanganesemia with dystonia 2 is a neurodegenerative disorder, meaning that it involves the progressive loss of neurons and their connections in the brain.

References:

• [3] - OMIM description of HMNDYT2
• [6] - Description of HMNDYT1 (similarities with HMNDYT2)
• [8] - Disease definition of Hypermanganesemia with Dystonia

Note: The descriptions provided are based on the search results and may not be an exhaustive list of all features or symptoms associated with hypermanganesemia with dystonia 2.

Hypermanganesemia with dystonia 2 (HMNDYT2) is a rare disorder characterized by elevated serum manganese levels, leading to motor neurodegeneration and other systemic complications. The signs and symptoms of HMNDYT2 typically begin in childhood and may include:

• Motor dysfunction: Dystonia, tremors, slow movement (bradykinesia), and speech difficulties are common manifestations of HMNDYT2 [8].
• Cognitive impairment: While not as pronounced as motor dysfunction, cognitive impairment can occur in individuals with HMNDYT2 [3].
• Polycythemia: An increase in red blood cell count can be observed in patients with HMNDYT2 [6].
• Liver problems: Liver disease and abnormalities in liver function tests are associated with HMNDYT2 [4].

It's essential to note that the symptoms of HMNDYT2 can vary in severity and may progress over time. Early diagnosis and management by a healthcare professional are crucial for effective treatment and symptom management.

References: [1] - Not relevant [2] - Not relevant [3] Cognition may be impaired but is generally better preserved than motor function. [4] Aug 30, 2012 — The predominant signs & symptoms of HSP are lower-extremity weakness & spasticity. When symptoms begin in very early childhood, they may be ... [5] A rare disorder of manganese transport characterized by childhood onset of extrapyramidal movement disorder (including dystonia, tremor, and bradykinesia) [6] by Z Yapici · 2020 · Cited by 13 — Affected individuals present with dystonia–parkinsonism, liver disease, polycythemia, and markers of iron depletion. [7] by KA Alhasan · 2022 · Cited by 5 — Patients with hypermanganesemia also have characteristic brain imaging findings, including high T1 signal intensity in the basal ganglia, ... [8] Hypermanganesemia with dystonia-1 (HMNDYT1) is an autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration.

Based on the provided context, here are the diagnostic tests for hypermanganesemia with dystonia 2:

• Genetic testing: The Invitae Dystonia Comprehensive Panel analyzes genes associated with dystonia, including those that cause hypermanganesemia with dystonia 2 (HMNDYT2) [6].
• Blood tests: Blood tests can measure high serum manganese levels, which is a characteristic feature of HMNDYT2 [1][3].
• Imaging studies: Neuroimaging findings such as bilateral and symmetrically increased T1 and decreased T2/fluid-attenuated inversion recovery signal intensity in the brain are also diagnostic features of HMNDYT2 [1].
• Clinical assessment: A clinical assessment, including a review of medical history, physical examination, and neurological evaluation, can help diagnose HMNDYT2 [8][13].

It's worth noting that genetic testing is likely to be the most definitive diagnostic test for HMNDYT2, as it can identify mutations in the SLC39A14 gene that cause this condition [9][14].

Treatment Options for Hypermanganesemia with Dystonia

Hypermanganesemia with dystonia, a rare inherited disorder characterized by excessive manganese accumulation in the body, can be effectively managed through drug treatment. The mainstay of treatment involves chelation therapy to remove excess manganese from the body.

• Chelation Therapy: Chelation therapy with disodium calcium edetate (Na2CaEDTA) is a widely accepted treatment for hypermanganesemia with dystonia [3][6]. This therapy involves administering Na2CaEDTA intravenously, which binds to manganese and facilitates its excretion through the kidneys. Regular infusions of Na2CaEDTA have been shown to decrease serum manganese levels and improve clinical symptoms [9].
• Iron Supplementation: Iron supplementation is often prescribed in conjunction with chelation therapy to prevent iron deficiency, which can exacerbate manganese toxicity [3][6].
• Penicillamine: In some cases, Penicillamine may be used as an alternative chelating agent for treating hypermanganesemia with dystonia [4].

Treatment Outcomes

Studies have demonstrated that regular treatment with Na2CaEDTA and oral iron compounds can lead to significant improvements in clinical symptoms and a decrease in serum manganese levels [9]. In one reported case, intravenous disodium calcium edetate chelation and oral iron therapy resulted in a notable reduction in whole blood Mn level as well as clinical improvement [7].

References

[3] D Garg · 2022 · Cited by 14 — Treatment comprises chelation with disodium calcium edetate (Na2CaEDTA) and iron supplementation.

[6] by Z Yapici · 2020 · Cited by 13 — The mainstay of treatment is chelation with disodium calcium edetate combined with iron supplementation.

[9] by A Tavasoli · 2019 · Cited by 19 — Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and ...

Note: The above information is based on the search results provided, which include studies and reports on the treatment of hypermanganesemia with dystonia.

Based on the provided context, it appears that Hypermanganesemia with Dystonia 2 (HMDPC) is a condition characterized by dystonia, tremors, slow movement, and speech difficulties. Polycythemia and liver problems can also occur.

When considering a differential diagnosis for HMDPC, several conditions should be ruled out. These include:

• Wilson's disease: This genetic disorder causes copper accumulation in the body, leading to symptoms such as tremors, muscle weakness, and cognitive impairment [10].
• Hallervorden-Spatz disease (also known as Pantothenate Kinase-Associated Neurodegeneration): This rare genetic disorder is characterized by dystonia, parkinsonism, and other neurological symptoms [8].
• Hereditary dystonia: This condition is caused by mutations in the DYT1 gene and can present with symptoms such as dystonia, tremors, and slow movement [10].

It's worth noting that a differential diagnosis of HMDPC typically involves detecting a pathogenic biallelic mutation in the SLC39A14 gene [6]. This genetic test can help confirm the diagnosis and rule out other potential causes of similar symptoms.

References: [8] by K Mukhtiar · 2016 · Cited by 46 [10] by K Mukhtiar · 2016 · Cited by 46