Leber plus disease

Leber Plus Disease: A Rare Inherited Mitochondrial Disorder

Leber plus disease, also known as LHON Plus, is a rare inherited mitochondrial disorder characterized by the clinical features of Leber hereditary optic neuropathy (LHON) in combination with other systemic or neurological abnormalities.

Clinical Features:

• Postural tremor: A type of tremor that occurs when standing or walking.
• Motor disorder: Difficulty with movement, coordination, and balance.
• Multiple sclerosis-like syndrome: Symptoms similar to multiple sclerosis, including demyelinating lesions in the central nervous system (CNS).
• Spinal cord disease: Damage to the spinal cord, which can lead to numbness, weakness, or paralysis of the limbs.
• Skeletal changes: Abnormalities in bone structure and function.
• Parkinsonism with dystonia: A combination of Parkinson's disease symptoms, such as tremors and stiffness, with dystonia (in

Leber "plus" disease, also known as LHON plus, is a rare inherited mitochondrial disorder that presents with additional signs and symptoms beyond the typical vision loss associated with Leber Hereditary Optic Neuropathy (LHON). The following are some of the common signs and symptoms of Leber "plus" disease:

• Vision loss: As in LHON, vision loss is typically the primary symptom of Leber "plus" disease. However, it may be accompanied by other systemic symptoms.
• Muscle weakness: Some individuals with Leber "plus" disease may experience muscle weakness or wasting, particularly in the proximal muscles (those closest to the trunk).
• Seizures: Seizures have been reported in some cases of Leber "plus" disease, although this is relatively rare.
• Cognitive impairment: There have been reports of cognitive impairment or dementia in individuals with Leber "plus" disease, although the exact prevalence and nature of these symptoms are not well understood.
• Cardiac abnormalities: Some studies have suggested that individuals with Leber "plus" disease may be at increased risk for cardiac abnormalities, such as cardiomyopathy or arrhythmias.

It's essential to note that the presentation of Leber "plus" disease can vary widely between individuals and even within families. Not everyone with this condition will experience all of these symptoms, and some may have additional symptoms not listed here.

References:

• [2] Blurring and clouding of vision are usually the first symptoms of LHON, which is also a characteristic of Leber "plus" disease.
• [4] Vision loss is typically the only symptom of LHON, but in cases of Leber "plus" disease, additional signs and symptoms may be present.
• [8] Leber hereditary optic neuropathy (LHON) is a rare inherited mitochondrial disorder that can also manifest as Leber "plus" disease with additional systemic symptoms.

Based on the provided context, here are the diagnostic tests for Leber hereditary optic neuropathy (LHON):

• Genetic testing: Molecular genetic testing for mitochondrial genes associated with LHON can be used to confirm diagnosis [3]. This test can detect mutations in mtDNA, such as m.11778G.A>MTND4, m.3460G.A>MT-ND1, and m.14484T.C>MT-ND6 [11].
• Blood testing for mtDNA assessment: Blood testing is used to assess the presence of mtDNA mutations in individuals without a known family history of LHON [5].
• Ophthalmologic examination: A baseline examination should include an ophthalmologic evaluation, including visual field (VF) testing, which is essential for diagnosis and monitoring visual function in various optic neuropathies [15].
• Optical Coherence Tomography (OCT): OCT imaging can be used to assess the health of the retina and optic nerve [4].
• Clinical Genetic Test: A clinical genetic test offered by Laboratorio de Genetica Clinica SL for conditions, including Leber optic atrophy, is available [7].

These diagnostic tests are used to confirm the presence or absence of LHON in individuals with symptoms and a suspected diagnosis.

Treatment Options for Leber Plus Disease

Leber plus disease, also known as Leber hereditary optic neuropathy (LHON), is a rare and inherited mitochondrial genetic disorder that affects the optic nerve, leading to severe visual disability. While there is no established medical treatment for LHON, recent emerging therapeutic options have shown promise in stabilizing and restoring vision.

Idebenone: A Promising Treatment Option

Idebenone, a short-chain benzoquinone analogue of coenzyme Q10, has been shown to be effective in treating patients with LHON. Studies have demonstrated that idebenone can stabilize and restore vision in patients treated within 1 year of onset of vision loss [2][3]. Idebenone is considered safe and effective for the treatment of patients with LHON [9].

Other Emerging Therapeutic Options

Recent emerging therapeutic options for LHON include genetic vector therapy, which is currently in phase III clinical trials. This innovative approach aims to address the underlying mitochondrial mutations that cause LHON.

Current Treatment Limitations

Currently, treatment options for LHON are limited to supportive measures and therapies with questionable benefits. Idebenone can be considered for patients early in the course of the disease [15].

Important Consideration

It is essential to note that idebenone treatment should be initiated during the acute phase of the disease and continue for at least one year following initiation, as recommended by some studies [1]. However, it is crucial to consult with a qualified specialist before initiating any treatment.

References:

[1] Shamsnajafabadi et al. (2023) - For VA improvement, idebenone treatment should be initiated during the acute phase of the disease and continue for at least one year following initiation. [2] Yu-Wai-Man et al. (2024) - Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. [3] Yu-Wai-Man et al. (2024) - Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. [9] Esmaeil et al. (2023) - An increasing body of published evidence indicates that idebenone is effective and safe for the treatment of patients with LHON. [15] Catarino et al. (2019) - Idebenone can be considered for the patient early in the course of the disease.

The differential diagnosis for Leber hereditary optic neuropathy (LHON) Plus, which refers to the rare cases where individuals with LHON exhibit extraocular manifestations, includes several conditions that can present with similar symptoms.

• Optic neuritis: This is an inflammation of the optic nerve that can cause pain and vision loss. It is often associated with multiple sclerosis or other demyelinating diseases.
• Wolfram syndrome: Also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), this rare genetic disorder affects the pancreas, kidneys, eyes, and ears. It can cause vision loss, hearing loss, and other systemic symptoms.
• Metabolic optic neuropathies: These are conditions that affect the optic nerve due to metabolic disorders, such as vitamin B12 deficiency or other nutritional deficiencies.
• Neuromyelitis Optica Spectrum Disorder (NMOSD): This is a rare autoimmune disease that affects the optic nerves and spinal cord. It can cause vision loss, weakness, and numbness in the limbs.
• MOG antibody-associated disease (MOGAD): This is another autoimmune disorder that affects the optic nerve and can cause vision loss.

These conditions often present with similar symptoms to LHON Plus, such as painless visual loss, optic atrophy, and extraocular manifestations. Therefore, a comprehensive differential diagnosis is essential to accurately diagnose LHON Plus and rule out other potential causes of these symptoms [1][2][3][4].

References: [1] - Search result 5: "Differential diagnosis includes optic neuritis, autosomal dominant optic atrophy (DOA), Wolfram syndrome, metabolic optic neuropathies (toxic, nutritional, and..." [2] - Search result 11: "In this context another important differential for LHON is represented by Neuromyelitis Optica Spectrum Disorder-optic neuritis and MOG antibody-associated disease (MOGAD)-optic neuritis in which the more frequent bilateral involvement, and the usual more severe visual outcome and severity of optic atrophy make the differential diagnosis more..." [3] - Search result 12: "Compressive and demyelinating lesions may cause edematous or atrophic optic nerves. Symptoms of a compressive lesion may include headache and changes in mood, personality, or memory." [4] - Search result 14: "LHON should be considered in the differential di-agnosis of any case of painless, unex-...