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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Children With Leukodystrophy
• Intervention / Treatment: Device: MRI

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Nagat Mohamed, Master; Phone Number: 01093952921; Email: ngat_mohamed_post@med.sohag.edu.eg
• Study Contact Backup: Name: Abdelraheem Abdrabu, Professor; Phone Number: 01065067057

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will include children with leukodystrophy diagnosed and followed-up at the pediatric neurology clinic of Sohag University Hospital during the period of the study.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White matter changes in MRI	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).	2 years
Biochemical changes	Arylsulfatase A levels can be measured in the leukocytes if suspected Metachromatic Leukodystrophy.; Galactocerebrosidase (GALC) enzyme level for Krabbe's Disease.; Plasma VLCFAs for Adrenoleukodystrophy.; NAA levels in the urine for Canavan's Disease.; Beta galactosidase in leukocytes deficient in cases of infantile GM1 gangliosidosis &Hexosaminidase for Tay Sachs disease.; Plasma FSH ,LH markedly reduced in cases of 4 H (Hypomyelination, hypodontia and hypogonadotropic hypogonadism syndrome).; Genetic testing for certain diseases	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrophysiological changes	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.	2 years
Tandem mass spectrometry (MS/MS) finding	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.	2 years
Urinary organic acid analysis	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.	2 years

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• Parikh S, Bernard G, Leventer RJ, van der Knaap MS, van Hove J, Pizzino A, McNeill NH, Helman G, Simons C, Schmidt JL, Rizzo WB, Patterson MC, Taft RJ, Vanderver A; GLIA Consortium. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Mol Genet Metab. 2015 Apr;114(4):501-515. doi: 10.1016/j.ymgme.2014.12.434. Epub 2014 Dec 29.
• Berger J, Moser HW, Forss-Petter S. Leukodystrophies: recent developments in genetics, molecular biology, pathogenesis and treatment. Curr Opin Neurol. 2001 Jun;14(3):305-12. doi: 10.1097/00019052-200106000-00007.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: Soh-Med-21-02-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No