mitochondrial DNA depletion syndrome 7

Mitochondrial DNA depletion syndrome-7 (MDDS-7) is a severe neurodegenerative disorder characterized by various symptoms, including:

• Hypotonia (low muscle tone)
• Ataxia (loss of coordination and balance)
• Ophthalmoplegia (weakness or paralysis of the eye muscles)
• Hearing loss
• Seizures

This condition is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

MDDS-7 is one of several subtypes of mitochondrial DNA depletion syndromes, which are characterized by a severe reduction in mitochondrial DNA content in affected tissues. This reduction leads to impaired energy production and cellular function, resulting in the various symptoms associated with MDDS-7.

It's worth noting that MDDS-7 is a rare condition, and more research is needed to fully understand its causes and effects on individuals who develop it.

References: * [2] Mitochondrial DNA depletion syndrome-7 is an autosomal recessive severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia ... * [3] Mitochondrial DNA depletion syndrome-7 is a severe neurodegenerative disorder characterized by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and ...

Mitochondrial DNA depletion syndrome-7 (MDDS-7) is a severe neurodegenerative disorder characterized by a range of symptoms, including:

• Hypotonia: Affected individuals typically present with low muscle tone, which can lead to weakness and fatigue [1].
• Ataxia: This condition is also associated with problems in coordination and balance, making it difficult for affected individuals to walk or maintain their posture [7].
• Ophthalmoplegia: Some people with MDDS-7 may experience weakness in the muscles that control eye movement, leading to droopy eyelids (ptosis) [8].
• Hearing loss: This condition can also affect hearing, making it difficult for affected individuals to hear or understand speech [4].
• Seizures: Seizures are another symptom associated with MDDS-7, which can range from mild to severe and may require medical attention [4].
• Microcephaly: Some affected individuals may have a smaller-than-average head size (microcephaly) [2].
• Lactic acidosis: This condition is also characterized by an accumulation of lactic acid in the blood, which can lead to fatigue, weakness, and other symptoms [2].

It's worth noting that the severity and progression of these symptoms can vary widely among affected individuals. In some cases, MDDS-7 may be associated with additional symptoms, such as tubulopathy (problems with kidney function) or failure to thrive (poor weight gain or loss of appetite) [2].

Diagnostic Tests for Mitochondrial DNA Depletion Syndrome 7

Mitochondrial DNA depletion syndrome-7 (MDDS-7) is a severe neurodegenerative disorder that requires prompt and accurate diagnosis to initiate effective treatment. The following diagnostic tests are commonly used to diagnose MDDS-7:

• 62 Gene Panel: A genetic test that assesses non-coding variants, including the maternally inherited mitochondrial genome [1]. This test is useful in diagnosing MDDS-7 by identifying mutations in the mitochondrial DNA.
• Mitochondrial DNA (mtDNA) Analysis: A quantitative test that measures mtDNA copy number in post-mitotic tissues [7]. This test helps to assess the severity of mtDNA depletion and can be used to monitor disease progression.
• Real-time Polymerase Chain Reaction (PCR): A molecular test used to analyze mtDNA content (copy number) [8]. This test is recommended for diagnosing mitochondrial diseases, including MDDS-7.
• Next-generation Sequencing (NGS) of the mtDNA Genome: A comprehensive genetic test that analyzes the entire mtDNA genome [3, 9]. This test is particularly useful in cases where targeted sequencing has failed to identify a diagnosis.

Additional Tests

In addition to these diagnostic tests, other investigations may be performed to rule out or confirm MDDS-7. These include:

• Imaging Studies: Such as MRI and CT scans, which can help to assess the extent of neurological involvement.
• Electroencephalography (EEG): A test that measures electrical activity in the brain, which can help to diagnose seizures and other neurological abnormalities.

References

[1] A 62 gene panel that includes assessment of non-coding variants. In addition, it also includes the maternally inherited mitochondrial genome. [3] Massively parallel sequencing/NGS of the mtDNA genome is the preferred methodology when testing mtDNA and should be performed in cases of suspected ... [7] Testing for mtDNA depletion​​ MtDNA depletion analysis is a quantitative test to assess mtDNA copy number in a clinically affected post-mitotic ... [8] Common tests for diagnosing mitochondrial disease · Real-time polymerase chain reaction (PCR) test used to analyze mtDNA content (copy number) · Recommended for ... [9] Jan 1, 2024 — mtDNA deletion and duplication testing should be performed in cases of suspected mitochondrial disease via NGS of the mtDNA genome, especially ...

Treatment Options for Mitochondrial DNA Depletion Syndrome

Mitochondrial DNA depletion syndrome (MDDS) is a rare genetic disorder that affects the mitochondria, the energy-producing structures within cells. While there are no specific treatments available for MDDS, various therapeutic approaches have been explored to manage its symptoms and slow disease progression.

Pharmacological Approaches

Several pharmacological interventions have been investigated as potential treatments for MDDS:

• Deoxyribonucleoside and deoxynucleotide treatments: These therapies aim to supplement the depleted mitochondrial DNA with exogenous nucleotides, thereby alleviating the energy crisis in cells. [7]
• Cofactor supplementation: Providing cofactors essential for mitochondrial function may help alleviate symptoms of MDDS. [6]

Other Treatment Options

In addition to pharmacological approaches, other treatment options have been explored:

• Dietary modulation: Modifying dietary intake to reduce oxidative stress and improve energy metabolism may be beneficial in managing MDDS symptoms.
• Liver transplantation: In some cases, liver transplantation has been considered as a treatment option for patients with severe mitochondrial disorders. [6]
• Stem cell transplantation: This approach involves replacing damaged cells with healthy stem cells, which can potentially restore normal mitochondrial function.

Emerging Therapies

Recent studies have highlighted the potential of emerging therapies in treating MDDS:

• Nucleoside therapy: Supplementing patients with exogenous deoxypyrimidines has shown promise as a treatment for TK2 deficiency, a subtype of MDDS. [3]
• Tailored therapies: These involve scavenging toxic compounds, administering deoxyribonucleosides or deoxynucleotides, cell replacement therapies, gene therapy, and other innovative approaches to address the underlying energy crisis in cells. [7]

While these treatment options hold promise, it is essential to note that MDDS is a complex disorder, and each patient's response to treatment may vary. Further research is needed to develop effective therapeutic strategies for this condition.

References:

[3] by E Dombi · 2024 · Cited by 2 [6] by O Hurko · 2013 · Cited by 14 [7] [7]

Mitochondrial DNA depletion syndrome (MDDS) encompasses a group of nuclear gene disorders affecting key enzymes involved in the synthesis of mtDNA and its maintenance [7]. The differential diagnosis for MDDS includes:

• Other mitochondrial diseases, such as Kearns-Sayre syndrome and myoclonic epilepsy with ragged-red fibers
• Metabolic disorders, including pyruvate dehydrogenase deficiency and carnitine palmitoyltransferase II deficiency
• Neurodegenerative disorders, like Leigh disease and infantile-onset spinocerebellar ataxia
• Liver diseases, such as Alagille syndrome and alpha-1 antitrypsin deficiency
• Other genetic disorders, including Fanconi anemia and Shwachman-Diamond syndrome

A multigene panel that includes FBXL4 and other genes related to mtDNA depletion syndromes may also be considered for differential diagnosis [2].

It's worth noting that the clinical presentation of MDDS can vary widely among affected individuals, making differential diagnosis challenging. A comprehensive diagnostic evaluation, including genetic testing and biochemical analysis, is often necessary to confirm a diagnosis of MDDS.

References: [7] N Keshavan · 2020 · Cited by 28 — Mitochondrial DNA depletion syndrome (MDDS) encompasses a group of nuclear gene disorders affecting key enzymes involved in the synthesis of mtDNA and its maintenance. [2] by M Almannai · 2017 · Cited by 17 — A multigene panel that includes FBXL4 and other genes related to mtDNA depletion syndromes (see Differential Diagnosis) may also be considered.