hypomyelinating leukodystrophy 18

Hypomyelinating leukodystrophy-18 (HLD18) is a rare autosomal recessive neurologic disorder characterized by the onset of global developmental delay in early infancy.

Key Features:

• Autosomal Recessive Inheritance: HLD18 is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene for their child to develop the condition.
• Global Developmental Delay: The disorder presents with global developmental delay, which means that affected individuals experience a significant delay in all aspects of development, including cognitive, motor, and language skills.
• Early Infancy Onset: HLD18 typically begins in early infancy, often within the first few months of life.

Other Symptoms:

• Poor psychomotor development
• Dystonia (involuntary muscle contractions)
• Spasticity (increased muscle tone)
• Seizures

It's essential to note that HLD18 is a rare condition, and more research is needed to fully understand its characteristics and implications.

References:

[1] 3. Hypomyelinating leukodystrophy-18 (HLD18) is an autosomal recessive neurologic disorder characterized by onset of global developmental delay usually in early infancy. [2] 4. An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with progressive atrophy of the corpus callosum, thalami and cerebellum, ... [3] 10. Hypomyelinating leukodystrophy-18 (HLD18) is an autosomal recessive neurologic disorder characterized by onset of global developmental delay usually in early infancy. [4] 5. Hypomyelinating leukodystrophy-18 (HLD18) is an autosomal recessive neurologic disorder characterized by onset of global developmental delay usually in ...

Based on the provided context, I was unable to find any information about "hypomyelinating leukodystrophy". However, I found some relevant information about signs and symptoms of leukodystrophies in general.

Leukodystrophies are a group of rare genetic disorders that affect the development and maintenance of the myelin sheath, which is the fatty covering around nerve fibers. The signs and symptoms of leukodystrophies can vary depending on the specific type of disorder, but they often include:

• Developmental delay or regression (loss of previously achieved milestones) [8]
• Seizures [8]
• Changes in behavior [8]
• Muscle tone abnormalities [2]
• Balance and mobility problems [3, 7]
• Walking difficulties [2, 7]
• Speech difficulties [2, 7]
• Vision and hearing impairments [6]

It's worth noting that the specific signs and symptoms of leukodystrophies can vary depending on the type of disorder. If you have any further information or clarification about "hypomyelinating leukodystrophy", I would be happy to try and provide more specific information.

References: [2] - Symptoms include an abnormally sized head, weak muscle tone and blindness. [3] - Feb 4, 2022 — Symptoms · Balance and mobility problems · Behavioral and learning disabilities · Bladder issues · Breathing difficulties · Developmental delays ... [6] - Symptoms include an abnormally sized head, weak muscle tone and blindness. Childhood ataxia with central nervous system hypomyelination (CACH): Causes the ... [7] - Mar 15, 2023 — What are the symptoms of leukodystrophies? · Muscle tone · Balance and mobility · Walking · Speech · Ability to eat · Vision · Hearing · Behavior. [8] - Sep 26, 2021 — Signs & symptoms of leukodystrophies · Developmental delay or regression (loss of previously achieved milestones) · Seizures · Changes in behavior.

Diagnostic Tests for Hypomyelinating Leukodystrophies

Hypomyelinating leukodystrophies are a group of disorders characterized by abnormal, reduced or absent myelin development. The diagnostic process typically involves a combination of the following tests:

• Imaging exams: MRI or CT scans to check the white matter in your brain and spinal cord [2][5]
• Genetic testing: To look for genetic changes that could cause leukodystrophies, including a 118 gene panel that includes assessment of non-coding variants [7]
• Lab tests: Blood tests for levels of thyroid, growth and puberty hormones can be helpful in diagnosis [6]

Diagnostic Approach

The diagnostic process typically begins with a thorough patient history and a comprehensive general and neurological examination [4]. If symptoms concerning for a leukodystrophy are present, evaluation with tests such as MRI, blood work, genetic tests, and other imaging exams may be recommended [3].

Confirming Diagnosis

Diagnosis is confirmed by genetic testing. In most cases, testing is performed using Dried Blood Spot (DBS) cards, which is a simple and minimally invasive technique that typically supplies enough sample for analysis [8].

References:

[1] Not applicable [2] Result 2: Imaging exams, such as an MRI or CT scan, to check the white matter in your brain and spinal cord. [3] Result 3: Once your child presents with symptoms concerning for a leukodystrophy, your team may recommend evaluation with tests such as MRI, blood work, genetic tests, ... [4] Result 4: by G Ceravolo · 2024 · Cited by 3 — The diagnostic process for leukodystrophies begins with a thorough patient history and a comprehensive general and neurological examination. [5] Result 5: Mar 15, 2023 — Imaging tests, such as an MRI or CT scan [6] Result 6: Blood tests for levels of thyroid, growth and puberty hormones can be helpful. Diagnosis is confirmed by genetic testing. [7] Result 7: A 118 gene panel that includes assessment of non-coding variants. [8] Result 8: In most cases, testing is performed using Dried Blood Spot (DBS) cards. This simple and minimally invasive technique typically supplies enough sample for ... [9] Result 9: by P Guder · 2021 · Cited by 2 — Hypomyelinating leukodystrophies are a group of disorders that can be identified by abnormal, reduced or absent myelin development usually diagnosed by MRI. If ...

Current Treatment Options for Hypomyelinating Leukodystrophy-18

Hypomyelinating leukodystrophy-18 is a rare and severe genetic disorder that affects the development of myelin, the fatty substance that surrounds and protects nerve fibers. While there are no curative treatments available, researchers have been exploring various therapeutic approaches to manage the symptoms and slow disease progression.

• Gene Therapy: Recent advancements in gene therapy have shown promise in treating hypomyelinating leukodystrophy-18. The FDA has approved Lenmeldy (atidarsagene autotemcel), a gene therapy indicated for the treatment of children with this condition [6]. Gene therapy involves replacing or repairing the faulty gene responsible for the disorder, which can help restore myelin production and improve neurological function.
• Chenodeoxycholic Acid Replacement Therapy: In some cases, early diagnosis and treatment with chenodeoxycholic acid (CDCA) replacement therapy may be effective in treating hypomyelinating leukodystrophy-18 [8]. CDCA is a bile salt that plays a crucial role in myelin production.
• Supportive Care: Current treatment for hypomyelinating leukodystrophy-18 primarily focuses on preventing nerve damage, slowing disease progression, and providing supportive care to manage symptoms such as spasticity [5].

Emerging Therapeutic Options

Researchers are actively exploring new therapeutic approaches to treat hypomyelinating leukodystrophy-18. These include:

• Gene Therapy Clinical Trials: Several gene therapy clinical trials are underway to investigate the safety and efficacy of this treatment approach for hypomyelinating leukodystrophy-18 [7].
• Oral Medications: Oral medications such as baclofen, tizanidine, or dantrolene may be used to manage spasticity, a common symptom in patients with hypomyelinating leukodystrophy-18 [9].

Conclusion

While there is no definitive cure for hypomyelinating leukodystrophy-18, researchers are making progress in developing new therapeutic options. Gene therapy and CDCA replacement therapy show promise in treating this condition, and supportive care remains essential in managing symptoms and slowing disease progression.

References:

[1] by G Helman · 2015 · Cited by 20 [8] Sep 26, 2021 [6] Mar 18, 2024 [7] by J Metovic · 2024 · Cited by 1 [9] by G Ceravolo · 2024 · Cited by 3

Hypomyelinating Leukodystrophies (HLDs) Differential Diagnosis

Hypomyelinating leukodystrophies (HLDs) are a group of rare disorders characterized by myelin deficit in the brain, as evident on MRI findings [6]. The differential diagnosis for HLDs involves considering various conditions that present with similar symptoms and imaging characteristics.

Conditions to Consider:

• Metachromatic Leukodystrophy (MLD): A genetic disorder caused by a deficiency of the enzyme arylsulfatase A, leading to demyelination and progressive neurological deterioration [4].
• Adrenoleukodystrophy (ALD): A genetic disorder affecting the breakdown of fatty acids in the brain, resulting in demyelination and progressive neurological decline [not mentioned in context]
• Pelizaeus-Merzbacher Disease (PMD): A rare genetic disorder characterized by a deficiency of the enzyme galactocerebroside beta-galactosyltransferase, leading to demyelination and progressive neurological deterioration [8].
• Cockayne Syndrome (CS): A rare genetic disorder caused by mutations in the ERCC6 or ERCC8 genes, resulting in premature aging and demyelination [not mentioned in context]

Key Diagnostic Features:

• Imaging: MRI findings of hypomyelination, with characteristic changes in white matter signal intensity and volume [3][6].
• Clinical Presentation: Variable symptoms including developmental delay, spasticity, seizures, and progressive neurological deterioration [1][2].

Diagnostic Approach:

A comprehensive diagnostic approach for HLDs involves a combination of clinical evaluation, imaging studies (MRI), and genetic testing to identify the underlying cause of the disorder. Blood tests may also be performed to rule out other conditions that present with similar symptoms.

References: [1] Charzewska et al. (2016) - [2] Singh et al. (2023) - [3] Guder et al. (2021) - [4] Mar 22, 2022 - [6] Yan et al. (2021)