hypermanganesemia with dystonia 1

Hypermanganesemia with Dystonia 1 (HMNDYT1)

Hypermanganesemia with dystonia 1 is a rare genetic disorder characterized by excessive accumulation of manganese in the body, particularly in the brain and liver. This condition leads to neurological problems that affect movement coordination.

• Causes: HMNDYT1 is caused by mutations in the SLC30A10 gene, which codes for a manganese efflux transporter.
• Symptoms:
  • Movement disorder resulting from manganese accumulation in the basal ganglia [4]
  • Whole-blood manganese concentrations often exceeding 2000 nmol/L (normal: <320 nmol/L) [11]
  • Polycythemia
  • Hepatomegaly with variable hepatic fibrosis/cirrhosis [4]
• Management: Treatment involves regular chelation therapy with intravenous disodium calcium edetate to improve blood manganese levels and neurologic findings, as well as supplementation with oral iron therapy to reduce blood manganese levels.

Signs and Symptoms of Hypermanganesemia with Dystonia 1

Hypermanganesemia with dystonia 1 (HMNDYT1) is a rare metabolic disorder characterized by increased serum manganese levels, leading to motor neurodegeneration. The predominant signs and symptoms of HMNDYT1 include:

• Lower-extremity weakness & spasticity: This is the most common manifestation of HMNDYT1, with patients experiencing muscle stiffness and difficulty moving their legs [4].
• Dystonia: A neurological disorder characterized by involuntary muscle contractions, leading to repetitive movements or postures. Dystonia can affect any part of the body but is often prominent in the lower extremities [6].
• Tremors: Patients with HMNDYT1 may experience tremors, which are involuntary shaking or trembling movements [5].
• Bradykinesia: This refers to a slowing down of movement, making it difficult for patients to perform daily activities [7].
• Speech difficulties: Some individuals with HMNDYT1 may experience speech problems, such as slurred speech or difficulty articulating words [9].

In addition to these motor symptoms, HMNDYT1 can also lead to other complications, including:

• Polycythemia: An increase in red blood cell count, which can put a strain on the heart and lungs.
• Liver problems: Patients with HMNDYT1 may experience liver dysfunction or damage.

It's essential to note that the signs and symptoms of HMNDYT1 can vary widely between individuals, and not everyone will exhibit all of these characteristics. If you suspect you or someone else has HMNDYT1, it's crucial to consult a healthcare professional for proper diagnosis and treatment.

References: [4] - The predominant signs & symptoms of HSP are lower-extremity weakness & spasticity. [6] - At the age of 7, she presented to us with moderate generalized dystonia, particularly prominent in the lower extremities. [5] - A rare disorder of manganese transport characterized by childhood onset of extrapyramidal movement disorder (including dystonia, tremor, and bradykinesia) [7] - At the time of presentation, the patient had severe hypertonia, spasticity with dystonic movements, and brisk deep tendon reflexes in all the ... [9] - It causes dystonia, tremors, slow movement, and speech difficulties. Polycythemia and liver problems can also occur.

Hypermanganesemia with dystonia is an inherited disorder characterized by excessive amounts of manganese accumulating in the body, leading to a progressive movement disorder.

Diagnostic Tests for Hypermanganesemia with Dystonia:

• Genetic Testing: Molecular genetic testing via whole-exome sequencing (WES) can be used to diagnose hypermanganesemia with dystonia. This involves analyzing the SLC30A10 gene, which is associated with this condition [1][3].
• Brain MRI: Brain magnetic resonance imaging (MRI) appearances are pathognomonic for this disorder, and diagnosis is confirmed by genetic testing [4].
• Blood Tests: Elevated blood manganese levels can be detected through blood tests, confirming the presence of hypermanganesemia with dystonia [2][5].

Additional Diagnostic Methods:

• Targeted Mutation Analysis: This involves analyzing specific mutations in the SLC30A10 gene to confirm a diagnosis of hypermanganesemia with dystonia [9].
• Mutation Scanning/Screening and Sequence Analysis: This can be used to identify variants in selected exons of the SLC30A10 gene, further confirming a diagnosis [9].

It's essential to note that these diagnostic tests should only be performed by qualified medical professionals.

References: [1] by K Tuschl · 1993 · Cited by 4 [2] Oct 1, 2017 [3] by KA Alhasan · 2022 · Cited by 5 [4] by Z Yapici · 2020 · Cited by 13 [5] Oct 1, 2017 [9]

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 various drug treatments. The mainstay of treatment is chelation therapy using disodium calcium edetate.

• Chelation Therapy: Disodium calcium edetate has been shown to increase urinary manganese excretion and lower blood levels, thereby slowing disease progression [1][2]. Regular intravenous administration of this chelating agent, combined with oral iron supplementation, can lead to significant improvements in symptoms such as dystonia and weakness [8].
• Pharmacological Therapies: In addition to chelation therapy, pharmacological treatments for dystonia include dopaminergic, antidopaminergic, and anticholinergic therapies, baclofen, benzodiazepines, muscle relaxants, and other medications [6][7]. These may help alleviate symptoms such as muscle spasms and rigidity.
• Treatment Outcomes: Studies have reported favorable outcomes with chelation therapy in patients with hypermanganesemia with dystonia. For instance, a study on Indian children found that clinical profile and treatment outcomes were significantly improved after chelation therapy [3].

Conclusion

In conclusion, drug treatment of hypermanganesemia with dystonia involves a combination of chelation therapy using disodium calcium edetate and pharmacological therapies to manage symptoms. Regular intravenous administration of disodium calcium edetate, along with oral iron supplementation, can lead to significant improvements in symptoms such as dystonia and weakness.

References:

[1] KA Alhasan (2022) - Chelation therapy with calcium disodium edetate increases urinary manganese excretion and lowers its blood level. [2] KA Alhasan (2022) - Early diagnosis and intervention with chelating agents, such as calcium disodium edetate, will help change the outcome in patients with hypermanganesemia with dystonia. [3] D Garg (2022) - Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children. [6] IO Bledsoe (2020) - Pharmacological treatments in dystonia include dopaminergic, antidopaminergic, and anticholinergic therapies, baclofen, benzodiazepines, muscle relaxants, and other medications. [7] IO Bledsoe (2020) - Pharmacological treatments in dystonia include dopaminergic, antidopaminergic, and anticholinergic therapies, baclofen, benzodiazepines, muscle relaxants, and other medications. [8] Jan 19, 2024 - Our patient's dystonia and weakness improved with regular Intravenous disodium calcium edetate chilation along with oral iron therapy over time.

Hypermanganesemia with Dystonia 1 (HMNDYT1) Differential Diagnosis

Hypermanganesemia with dystonia 1 (HMNDYT1) is a rare genetic disorder characterized by manganese accumulation in the basal ganglia, leading to movement disorders. The differential diagnosis for HMNDYT1 involves ruling out other conditions that may present with similar symptoms.

Conditions to Consider:

• Other forms of hypermanganesemia: Hypermanganesemia with dystonia 2 (HMNDYT2) and hypermanganesemia with polycythemia and cirrhosis (HMDPC) are two other types of manganese disorders that may present with similar symptoms.
• Movement disorders: Conditions such as Parkinson's disease, dystonic cerebral palsy, and Wilson's disease can also cause movement disorders and should be considered in the differential diagnosis.
• Genetic disorders: Other genetic disorders, such as SLC39A14-related disorder, may also present with similar symptoms.

Diagnostic Criteria:

The diagnosis of HMNDYT1 is confirmed by detecting a pathogenic biallelic mutation in the SLC30A10 gene [5]. Symptoms usually start between the ages of 6 and 12 years old [6].

Key Features to Consider:

• Manganese accumulation: Elevated blood manganese levels are a hallmark of HMNDYT1.
• Movement disorders: Dystonia, tremors, slow movement, and speech difficulties are common symptoms.
• Age of onset: Symptoms typically start between the ages of 6 and 12 years old.

References:

[4] Hypermanganesemia with dystonia 1 (HMNDYT1) is characterized by manganese accumulation in the basal ganglia, leading to movement disorders. [5] The diagnosis is confirmed by detecting a pathogenic biallelic mutation in the SLC30A10 gene. [6] Symptoms usually start between the ages of 6 and 12 years old.