ORIGINAL ARTICLE Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme emerging M. A. Aldahmesh & Z. N. Al-Hassnan & M. Aldosari & F. S. Alkuraya Received: 24 December 2008 / Accepted: 25 February 2009 / Published online: 10 March 2009 # Springer-Verlag 2009 Abstract Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal neurodegenerative disorders that have in common the characteristic accumulation of abnormal storage material. Old clinical classification based on age of onset is now being revisited with the quickly accumulating knowledge of the various genetic defects that underlie this group of genetically heterogeneous disorders. We report our linkage data on a family with late-infantile NCL and show that the disease in this family is due to a homozygous novel mutation in the most recently described NCL gene (MFSD8). We use clinical data from our patients and the few others that have previously been reported to delineate the phenotype associ- ated with mutations in this gene. We conclude that the phenotype is fairly consistent, which is a helpful guide to clinicians as they decide on the most cost-effective molecular testing strategies for NCLs. Keywords Turkish variant . Late-infantile NCL . Missense . Retinitis pigmentosa-like . Seizures Introduction Neuronal ceroid lipofuscinosis (NCL) was originally de- scribed in the nineteenth century as one disease with variable age of onset and a spectrum of neurological phenotypes [2]. NCL is now known to be a rare (1:12,500 live births), clinically and genetically heterogeneous group of neurode- generative disorders characterized by the intracellular accu- mulation of autofluorescent lipopigment storage material in different patterns [2]. Being a lysosomal-storage group of disorders, the progressive nature of NCL is typical and manifests clinically as worsening mental and motor disability, seizures, and early death. Visual loss is a common feature and may be the presenting symptom [5]. A clinical classification that is based on the age of onset and the type of accumulating storage material has been in place for a long time. However, the last decade has witnessed the identification of the genetic defects that underlie the majority of NCL cases and the boundaries between the once discrete clinical subtypes are now viewed to be largely artificial [5]. Late-infantile NCL (LINCL) is among the most genetically heterogeneous subtypes of NCL with mutations in most of the eight known NCL genes have been reported [4]. The recent discovery that mutations in MFSD8 can cause a particular variant called the Turkish variant LINCL (vLINCL), characterized by a later age of onset and a more severe seizure phenotype, brings to eight the number of NCL genes identified to date [6]. Neurogenetics (2009) 10:307–311 DOI 10.1007/s10048-009-0185-1 M. A. Aldahmesh : F. S. Alkuraya (*) Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia e-mail: falkuraya@kfshrc.edu.sa Z. N. Al-Hassnan Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Z. N. Al-Hassnan : F. S. Alkuraya Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia M. Aldosari Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia F. S. Alkuraya Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia