Characterization and Outcome of Children With Leukodystrophy: An Observational Study at Sohag University Hospital

• Conditions: Children With Leukodystrophy

• Registration Number: NCT04781010
• Lead Sponsor: Sohag University

Brief Summary

Leukodystrophies are heterogeneous genetic disorders characterized by the selective involvement of white matter in the central nervous system (CNS) (1, 2). Inherited leukodystrophies are diseases of the myelin, including abnormal myelin development, hypomyelination, or degeneration of myelin (3, 4).

Most of these disorders fall into one of three categories; lysosomal storage diseases, peroxisomal disorders, and diseases caused by mitochondrial dysfunction and each leukodystrophy has distinctive clinical, biochemical, pathologic, and radiologic features (5).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-24
• Status Verified: 2021-03
• Study Start: 2021-03-01
• Study First Submitted QC: 2021-03-02
• Last Update Submitted: 2021-03-02
• Study First Posted: 2021-03-04
• Last Update Posted: 2021-03-04
• Primary Completion: 2023-03-31
• Study Completion: 2023-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• The patients fulfilling all the following criteria will be included:

  1. Age ≤ 18 years.
  2. The presence of typical clinical, biochemical, and neuroimaging features of leukodystrophies.

Exclusion Criteria

• 1- Children who have coexistent genetic disorders. 2- Children who have cerebral malformations. 3- History of perinatal asphyxia. 4- History of head trauma or intracranial hemorrhage. 5- Acquired CNS myelin disorders, such as multiple sclerosis and related acquired demyelinating processes, infectious and post-infectious white matter damage, toxic injuries and non-genetic vascular insults.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Biochemical changes	2 years	1. Arylsulfatase A levels can be measured in the leukocytes if suspected Metachromatic Leukodystrophy.; 2. Galactocerebrosidase (GALC) enzyme level for Krabbe's Disease.; 3. Plasma VLCFAs for Adrenoleukodystrophy.; 4. NAA levels in the urine for Canavan's Disease.; 5. Beta galactosidase in leukocytes deficient in cases of infantile GM1 gangliosidosis \&Hexosaminidase for Tay Sachs disease.; 6. Plasma FSH ,LH markedly reduced in cases of 4 H (Hypomyelination, hypodontia and hypogonadotropic hypogonadism syndrome).; 7. Genetic testing for certain diseases
White matter changes in MRI	2 years	Brain MRI of all patients will be systematically reviewed, particularly Sagittal T1, Axial T1, T2-weighted and fluid-attenuated inversion-recovery (FLAIR) sequences. Other sequences will be also reviewed if available, such as MR spectroscopy (MRS) (for mitochondrial disorders or Canavan disease to investigate abnormalities in lactate or N-acetyl aspartate (NAA) respectively), and diffusion-weighting (useful in disorders such as AARS2-related leukoencephalopathy).

Secondary Outcome Measures

Name	Time	Method
Urinary organic acid analysis	2 years	by GC/MS using agilent 7890 and 5975 systems. Results will be calculated in mol/mmol creatinine using acalipration curve of the organic acid of interest that will be processed under the same conditions.
Electrophysiological changes	2 years	including nerve conduction studies and electromyography will be useful in identifying peripheral nerve involvement (e.g., in AMN, MLD, Krabbe) or myopathy with or without a neuropathy (e.g., in mitochondrial diseases) or metachromatic leukodystrophy. Moreover, electroencephalographic data will be assessed, particularly in patients with seizures.
Tandem mass spectrometry (MS/MS) finding	2 years	We will obtain patients' blood samples on a Glutheric card, Acylcarnitines and amino acids will be analysed using ACQUTIY TQD Tandem quadrupole UPLC/MS/MS with apositive electrospray ionization prope according to the manufacturer's instructions.