Clinical and Molecular Characteristics of Neuronal Ceroid Lipofuscinosis in Saudi Arabia.
Consanguinity
Inherited metabolic diseases
Neuronal ceroid lipofuscinoses
Next-generation sequencing
Recessive diseases
Saudi Arabia
Journal
Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183
Informations de publication
Date de publication:
07 Mar 2024
07 Mar 2024
Historique:
received:
04
10
2022
revised:
15
02
2024
accepted:
03
03
2024
medline:
24
4
2024
pubmed:
24
4
2024
entrez:
23
4
2024
Statut:
aheadofprint
Résumé
Neuronal ceroid lipofuscinoses (NCLs) represent a heterogeneous group of inherited metabolic lysosomal disorders characterized by neurodegeneration. This study sought to describe the clinical and molecular characteristics of NCLs in Saudi Arabia and determine the most common types in that population. A retrospective review of electronic medical records was conducted for 63 patients with NCL (55 families) from six tertiary and referral centers in Saudi Arabia between 2008 and 2022. Clinical, radiological, and neurophysiological data as well as genetic diagnoses were reviewed. CLN6 was the predominant type, accounting for 45% of cases in 25 families. The most common initial symptoms were speech delay (53%), cognitive decline (50%) and/or gait abnormalities (48%), and seizure (40%). Behavioral symptomatology was observed in 20%, whereas visual impairment was less frequently (9.3%) encountered. Diffuse cerebral and cerebellar atrophy was the predominant finding on brain magnetic resonance imaging. Electroencephalography generally revealed background slowing in all patients with generalized epileptiform discharges in 60%. The most common genotype detected was the p.Ser265del variant found in 36% (20 of 55 families). The most rapidly progressive subtypes were CLN2 and CLN6. Two patients with each died at age five years. The earliest age at which a patient was nonambulatory was two years in a patient with CLN14. This is the largest molecularly confirmed NCL cohort study from Saudi Arabia. Characterizing the natural history of specific NLC types can increase understanding of the underlying pathophysiology and distinctive genotype-phenotype characteristics, facilitating early diagnosis and treatment initiation as well as genetic counseling for families.
Sections du résumé
BACKGROUND
BACKGROUND
Neuronal ceroid lipofuscinoses (NCLs) represent a heterogeneous group of inherited metabolic lysosomal disorders characterized by neurodegeneration. This study sought to describe the clinical and molecular characteristics of NCLs in Saudi Arabia and determine the most common types in that population.
METHODS
METHODS
A retrospective review of electronic medical records was conducted for 63 patients with NCL (55 families) from six tertiary and referral centers in Saudi Arabia between 2008 and 2022. Clinical, radiological, and neurophysiological data as well as genetic diagnoses were reviewed.
RESULTS
RESULTS
CLN6 was the predominant type, accounting for 45% of cases in 25 families. The most common initial symptoms were speech delay (53%), cognitive decline (50%) and/or gait abnormalities (48%), and seizure (40%). Behavioral symptomatology was observed in 20%, whereas visual impairment was less frequently (9.3%) encountered. Diffuse cerebral and cerebellar atrophy was the predominant finding on brain magnetic resonance imaging. Electroencephalography generally revealed background slowing in all patients with generalized epileptiform discharges in 60%. The most common genotype detected was the p.Ser265del variant found in 36% (20 of 55 families). The most rapidly progressive subtypes were CLN2 and CLN6. Two patients with each died at age five years. The earliest age at which a patient was nonambulatory was two years in a patient with CLN14.
CONCLUSIONS
CONCLUSIONS
This is the largest molecularly confirmed NCL cohort study from Saudi Arabia. Characterizing the natural history of specific NLC types can increase understanding of the underlying pathophysiology and distinctive genotype-phenotype characteristics, facilitating early diagnosis and treatment initiation as well as genetic counseling for families.
Identifiants
pubmed: 38653183
pii: S0887-8994(24)00079-1
doi: 10.1016/j.pediatrneurol.2024.03.004
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
149-155Investigateurs
Amal Kentab
(A)
H H Muddathir
(HH)
M A Salih
(MA)
Aziza M Mushiba
(AM)
A P Zada
(AP)
Mohammed S Bamajboor
(MS)
Sadique Zameer
(S)
Fahad AlBassam
(F)
Adel Mahmoud
(A)
A A Alnawfal
(AA)
Mushari AlAmr
(M)
Maryam Bawazir
(M)
Ahmed Al Rumayyan
(A)
Waleed Al-Twaijri
(W)
Muhammed Talal Alrifai
(MT)
Sumayah Al Hajjaj
(S)
Informations de copyright
Copyright © 2024 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following competing interests: Mohammed M. Saleh, Abdulrahim M. Hamhom, Ali AlOtaibi, Malak AlGhamdi, Yousef Housawi, Yaser I. Aljadhai, Seham Alameer, Mohammed Almannai, Lamyaa Ali Jad, Ali H. AlWadie, Sadia Tabassum, Abdulaziz Alsaman, Ali AlAsmari, Fuad Al Mutairi, Hamad Althiyab, Fahad A. Bashiri, Suzan AlHumaidi, Majid Alfadhel, and Aqeela AlHashim have no conflicts of interest to declare. Jonathan W. Mink is in receipt of research funding from Theranexus, Inc, Neurogene Inc, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; is a consultant for the Beyond Batten Disease Foundation, Amicus, Inc, Polaryx, Inc, and TEVA, Inc; is a member of Data and Safety Monitoring Board for PTC Therapeutics and Passage Bio; and is a Trial Steering Committee for Applied Therapeutics. Eissa A. Faqeih is in receipt of a research grant from the Intramural Research Fund for an extended project to study common genetic diseases in Saudi Arabia (Demography of Recessive Diseases in KSA; Grant #019-052).