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hypomyelinating leukodystrophy 17

Description

Hypomyelinating leukodystrophy-17 (HLD17) is a rare and severe neurodevelopmental disorder characterized by poor or no development apparent from infancy [2][3][4]. Affected individuals never learn to walk or speak, and have early-onset multifocal seizures, spasticity, poor overall growth, and microcephaly (up to -10 SD) [3].

Brain imaging shows multiple abnormalities, including cerebral and cerebellar atrophy [3]. The disorder is inherited in an autosomal recessive manner, meaning that both parents must carry a mutated gene for their child to be affected.

The symptoms of HLD17 typically become apparent from infancy, with affected individuals failing to develop normally. They may experience developmental delays, hypotonia (low muscle tone), ataxia (loss of coordination), and other neurological problems [10][11].

It's worth noting that the clinical presentation can vary, and some cases may have a milder onset in adolescence or adulthood [12]. However, severe forms of HLD17 typically present in infancy or early childhood.

References: [2] - Hypomyelinating leukodystrophy-17 is an autosomal recessive neurodevelopmental disorder characterized by poor, if any, development apparent from infancy. ... (summary by Shukla et al., 2018). [3] - Affected individuals never learn to walk or speak, and have early-onset multifocal seizures, spasticity, poor overall growth, and microcephaly (up to -10 SD). Brain imaging shows multiple abnormalities, including cerebral and cerebellar ... [4] - Hypomyelinating leukodystrophy-17 (HLD17) is an autosomal recessive neurodevelopmental disorder characterized by poor, if any, development apparent from infancy. ... For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. [10] - Hypomyelinating leukodystrophies constitute a subset of genetic white matter disorders characterized by a primary lack of myelin deposition. Most patients with severe hypomyelination present in ... [11] - Hypomyelinating leukodystrophies constitute a subset of genetic white matter disorders characterized by a primary lack of myelin deposition. Most patients with severe hypomyelination present in infancy or early childhood and develop severe neurological deficits, but the clinical presentation can also be mild with onset of symptoms in adolescence or adulthood. [12] - Hypomyelinating leukodystrophies constitute a subset of genetic white matter disorders characterized by a primary lack of myelin deposition. Most patients with severe hypomyelination present in infancy or early childhood and develop severe neurological deficits, but the clinical presentation can also be mild with onset of symptoms in adolescence or adulthood.

Additional Characteristics

  • spasticity
  • developmental delays
  • ataxia (loss of coordination)
  • hypotonia (low muscle tone)
  • severe neurological deficits
  • poor or no development apparent from infancy
  • never learn to walk or speak
  • early-onset multifocal seizures
  • poor overall growth
  • microcephaly (up to -10 SD)

Signs and Symptoms

Common Signs and Symptoms of Hypomyelinating Leukodystrophy-17 (HLD17)

Hypomyelinating leukodystrophy-17 (HLD17) is a rare neurodevelopmental disorder characterized by poor or absent development of the myelin sheath, which surrounds and protects nerve fibers. The signs and symptoms of HLD17 can vary in severity and may include:

  • Early-onset seizures: Seizures are a common feature of HLD17, often appearing early in life [2].
  • Spasticity (muscle tightness): Affected individuals may experience muscle stiffness or rigidity, which can lead to difficulties with movement and coordination [4].
  • Poor growth: Children with HLD17 may exhibit poor growth patterns, including microcephaly (small head size) [6].
  • Microcephaly: A small head size is a characteristic feature of HLD17 [6].
  • Early-onset developmental delays: Affected individuals may experience significant delays in reaching developmental milestones, such as sitting, standing, or walking [7].
  • Cerebral and cerebellar atrophy: Brain imaging studies have shown abnormalities in the cerebral and cerebellar regions, including thinning of the corpus callosum [3].

Additional Symptoms

Other symptoms associated with HLD17 may include:

  • Hypsarrhythmia: A specific type of brain wave pattern that is often seen in individuals with HLD17 [1].
  • Paresthesias (abnormal sensations): Affected individuals may experience abnormal sensations, such as burning or electric shock-like pain, which can be localized to one or both hands or legs [9].

References

[1] Clinical features · Absent speech · Cerebellar atrophy · Cerebral atrophy · Hyperreflexia · Hypoplasia of the corpus callosum · Hypsarrhythmia · Inability to walk ...

[2] Mar 22, 2022 — Symptoms of metachromatic leukodystrophy may include seizures, personality changes, spasticity, progressive dementia, painful paresthesias ...

[3] Brain imaging shows multiple abnormalities, including cerebral and cerebellar atrophy, thin corpus callosum, abnormal signals in the basal ganglia, and features ...

[4] SIGNS AND SYMPTOMS · Seizures · Spasticity (muscle tightness) · Growth difficulties · Bowel and bladder problems · Pain · Drooling · Teeth grinding · Sleep difficulties ...

[5] Hypomyelinating leukodystrophy-17 (HLD17) is an autosomal recessive neurodevelopmental disorder characterized by poor, if any, development apparent from ...

[6] Affected individuals never learn to walk or speak, have early-onset seizures, spasticity, poor growth, and microcephaly. Brain imaging shows abnormalities such ...

[7] by MRZ Ruzhnikov · 2021 · Cited by 2 — Early presenting features can be nonspecific and masquerade as common pediatric complaints, including inattention, irritability, or motor delays.

[8] Leukodystrophy is characterized by specific symptoms, including decreased motor function, muscle rigidity, and eventual degeneration of sight and hearing.

[9] For top-notch custom large format printing, graphics, vinyl signs, architectural signage, retail signs, institutional signs, and a wide range of indoor and outdoor business identification solutions, trust Casco Signs.

Additional Symptoms

  • Microcephaly
  • Hypsarrhythmia
  • Early-onset seizures
  • Poor growth
  • Spasticity (muscle tightness)
  • Early-onset developmental delays
  • Cerebral and cerebellar atrophy
  • Paresthesias (abnormal sensations)

Diagnostic Tests

Based on the available information, it appears that diagnostic tests for hypomyelinating leukodystrophy (HLD) are crucial for confirming a diagnosis.

  • MRI and genetic testing are considered essential for diagnosing HLD. Molecular testing is pursued when a diagnosis is suspected, particularly in cases where clinical suspicion is high [5].
  • A comprehensive genetic investigation, including MLPA targeted analysis, can be useful for the molecular diagnosis of HLDs [7]. This may involve assessing non-coding variants and the maternally inherited mitochondrial genome.
  • In some cases, a 118 gene panel that includes assessment of non-coding variants may be used to aid in diagnosis.

It's worth noting that diagnosing adult leukodystrophies remains complex and challenging, and clinicians and radiologists should recognize MRI white matter involvement as an important diagnostic clue [9].

In terms of specific tests, deletion/duplication analysis is one of the molecular genetics tests available for this condition [1]. However, it's essential to consult with a healthcare professional or a genetic counselor to determine the most appropriate diagnostic approach for an individual case.

References: [1] Available tests. 7 tests are in the database for this condition. [5] by G Ceravolo · 2024 · Cited by 3 — MRI and genetic testing are crucial for confirming the diagnosis of leukodystrophy. [7] by H Yan · 2021 · Cited by 34 — The comprehensive genetic investigation is useful for the molecular diagnosis of HLDs. [9] by LL Resende · 2019 · Cited by 77 — Diagnosing adult leukodystrophies remains complex and challenging.

Additional Diagnostic Tests

  • Genetic testing
  • MRI
  • Molecular testing
  • duplication analysis
  • Comprehensive genetic investigation
  • MLPA targeted analysis
  • 118 gene panel

Treatment

Current Treatments for Hypomyelinating Leukodystrophy 17

Hypomyelinating leukodystrophy 17 (HLD17) is a rare genetic disorder that affects the development of myelin, the fatty substance that surrounds and protects nerve fibers. While there are no specific treatments available to cure HLD17, several options can help manage symptoms and slow disease progression.

  • Chenodeoxycholic acid replacement therapy: This treatment has been shown to be effective in treating another form of leukodystrophy called CTX (cerebrotendinous xanthomatosis) if diagnosed early [8]. However, its effectiveness for HLD17 is not well established.
  • Gene therapies: Several gene therapies are being developed for various forms of leukodystrophies, including HLD17. These treatments aim to replace or repair the faulty genes responsible for the condition [7], [9].
  • Supportive care and symptom management: This includes managing symptoms such as spasticity through oral medications like baclofen, tizanidine, or dantrolene [10]. Additionally, supportive care measures can help prevent complications and improve quality of life.

Emerging Therapies

Recent developments in gene therapy have shown promise for treating leukodystrophies. For example, the FDA-approved gene therapy Lenmeldy (atidarsagene autotemcel) has been indicated for the treatment of children with a specific form of leukodystrophy [4]. While this treatment is not specifically approved for HLD17, it may provide hope for future therapeutic options.

Current Research and Future Directions

Research into gene therapies and other treatments for leukodystrophies continues to advance. A comprehensive review of gene therapy clinical trials for leukodystrophy patients has been published, highlighting the need for further research in this area [9]. As our understanding of these complex disorders grows, new therapeutic options may become available.

References:

[7] - Medicinal treatments are sometimes possible, as in the case of cerebrotendinous xanthomatosis.Several gene therapies are also being developed for ... [8] - Sep 26, 2021 — If it's diagnosed early, one type of leukodystrophy called CTX can be treated with chenodeoxycholic acid (CDCA) replacement therapy. [9] - by J Metovic · 2024 · Cited by 1 — We present an updated and comprehensive review of all gene therapy clinical trials for leukodystrophy patients in the context of disease-specific ... [10] - by G Ceravolo · 2024 · Cited by 3 — Managing spasticity, a prevalent problem in leukodystrophies, can be accomplished through oral medications, such as baclofen, tizanidine, or ...

Recommended Medications

  • Gene therapies
  • Chenodeoxycholic acid replacement therapy
  • Supportive care and symptom management

💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.

Differential Diagnosis

Hypomyelinating leukodystrophies (HLDs) are a group of rare disorders characterized by myelin deficit in the brain, as per [4]. The differential diagnosis of HLDs involves considering various conditions that present with similar clinical and radiological features.

The following conditions should be considered in the differential diagnosis of HLDs:

  • Pelizaeus-Merzbacher disease (PMD): A genetic disorder caused by mutations in the PMD gene, leading to a deficiency of myelin basic protein [1].
  • Allan-Herndon-Dudley syndrome: A rare X-linked disorder characterized by hypomyelination and atrophy of the basal ganglia and cerebellum [7].
  • POLR3-Related Leukodystrophy: A genetic disorder caused by mutations in the POLR3A or POLR3B genes, leading to a deficiency of myelin basic protein [2].
  • Cockayne syndrome: A rare genetic disorder characterized by premature aging, sun sensitivity, and cognitive decline [7].

The diagnostic pathway for HLDs involves clinical examination, radiological imaging (e.g., MRI), and genetic testing. The following steps are typically taken:

  1. Clinical examination to assess developmental and/or neurological symptoms [3].
  2. Radiological imaging (e.g., MRI) to evaluate the extent of myelin deficit in the brain [4].
  3. Genetic testing to identify mutations in genes associated with HLDs, such as PMD or POLR3-Related Leukodystrophy [1, 2].

Early childhood onset and cerebellar involvement are key features that may suggest a diagnosis of SLC17A5-related leukodystrophy [2].

Additional Information

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A hypomyelinating leukodystrophy characterized by onset in early infancy of microcephaly and lack of overall development that has_material_basis_in homozygous mutation in the AIMP2 gene on chromosome 7p22.
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