No abstract available.
Electroencephalography* ; Neuronal Ceroid-Lipofuscinoses ; Neurons*

The neuronal ceroid lipofuscinoses correspond to a group of disorders characterized by neurodegeneration and intracellular buildup of auto-flourescent lipopigment (ceroid lipofuscin). They are classified by age of onset into infantile, late infantile, juvenile and adult forms. Among these, the late infantile type is caused by mutations in tripeptidyl peptidase 1 (TPP1) gene and is characterized by age of onset between 2-4 years, seizures, early progressive cognitive impairment and visual loss. Our patient is a 4-year-old girl who presented at 2 years and 10 months old with seizures followed by ataxia, regression of skills and eventual visual decline. TPP1 enzyme activity was below normal for age. This report aims to increase the awareness of physicians on the cluster of symptoms characteristic of this disorder which will help facilitate early diagnosis and prompt institution of appropriate management.
Neuronal Ceroid-Lipofuscinoses ; Cognitive Dysfunction

The neuronal ceroid-lipofuscinosis (NCL) is a group of progressive,. Inherited neurodegenerative diseases characterized by the deposition of large numbers o autofluorescent cytosomes in most tissues. Based on the age at onset, clinical presentation, and morphological findings, NCL is divided into four subgroups: infantile, late inf antile, juvenile and adult types. Late inf antile NCL is characterized by age of onset 2.5-4 years, early seizure, frequent myoclonic jerk, late visual failure, whereas juvenile NCL by age of onset 4-7 years, early visual failure, late seizure, infrequent myoclonic jerks. We experienced unusual form of NCL as diagnosed by tissue biopsy. The patient is a 11 years old with a mixture form of juvenile and late infantile NCL, being called early juvenile NCL.
Adult ; Age of Onset ; Biopsy ; Child ; Humans ; Myoclonus ; Neurodegenerative Diseases ; Neuronal Ceroid-Lipofuscinoses* ; Seizures

Child ; Developmental Disabilities ; diagnosis ; Humans ; Intellectual Disability ; diagnosis ; Male ; Neuronal Ceroid-Lipofuscinoses ; diagnosis

OBJECTIVE: To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7). METHODS: A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed. RESULTS: The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7. CONCLUSION Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.
Male ; Female ; Humans ; Membrane Transport Proteins/genetics* ; Neuronal Ceroid-Lipofuscinoses/diagnosis* ; Retrospective Studies ; Atrophy ; Mutation

OBJECTIVE: To analyze the genetic cause of a family with autosomal recessive neuronal ceroid lipofuscinoses (NCL). METHODS: The proband was screened for mutations within the coding region of the candidate genes through high-throughput targeted sequencing. Potential causative mutations were verified by PCR and Sanger sequencing in the proband and his parents. RT-PCR and TA clone sequencing were performed to investigate whether the mRNAs were abnormally spliced. RESULTS: The sequencing results revealed compound heterozygous mutations of :c.486+2T>C and c.486+4A>T, which were respectively inherited from his parents. RT-PCR and TA cloning sequencing suggested that the mRNAs were abnormally spliced in two forms due to both mutations. CONCLUSIONS The compound heterozygous mutations of :c.486+2T>C and c.486+4A>T are possibly the genetic causes of the NCL family. Detection of the novel mutation has extended mutation spectrum of .
Alternative Splicing ; Female ; Humans ; Male ; Membrane Proteins ; genetics ; Mutation ; Neuronal Ceroid-Lipofuscinoses ; genetics

OBJECTIVE: To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferritinemia cataract syndrome (HHCS). METHODS: A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification. RESULTS: The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2417.70 ng/mL, reference range: 30 ~ 400 ng/ml). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c.280A>C and c.124-124+3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c.-160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS. CONCLUSION The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.
Child, Preschool ; Humans ; Male ; Cataract/genetics* ; Genetic Testing ; Mutation ; Neuronal Ceroid-Lipofuscinoses/pathology* ; Vision Disorders/genetics*

Neuronal ceroid lipofuscinoses (NCL) are the most common childhood neurodegenerative disorders. Clinical features include seizures, blindness, psychomotor deterioration, the age of onset differ for each NCL type. Diagnosis of late infantile NCL relies on the characteristic clinical presentation, electrophysiological and neuroradiological findings, and identification of the ultrastructural abnormalities. The Photoparoxsmal response provide diagnostic clues to an atypical case of Infantile NCL in which results of extraneuronal biopsies were negative and MRI findings resembles leukodystrophy. Photic stimulation with 2 to 5 Hz activity elicited discrete spike and wave discharges in the occipital region on electroencephalogram and no sleep spindles are present. In patients with rapid neurologic deterioration, diagnosis of NCL should be considered and an EEG must be performed using photic stimulation to look for characteristic findings.
Age of Onset ; Biopsy ; Blindness ; Diagnosis ; Electroencephalography* ; Humans ; Magnetic Resonance Imaging ; Neurodegenerative Diseases ; Neuronal Ceroid-Lipofuscinoses* ; Photic Stimulation ; Seizures

Neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative disorders, which are caused by the accumulation of lipopigment in lysosomes. Variant forms of late infantile NCLs (vLINCLs) characterized by a later onset of seizures and visual impairment (3–8 years) than in the classic form (2–4 years) are caused by mutations of the gene encoding ceroid lipofuscinosis neuronal protein 6 (CLN6). In a girl with progressive myoclonus epilepsy, we found heterozygous variants of CLN6 (NM_017882.2; NP_060352.1): c.296A>G (p.Lys99Arg) and c.307C>T (p.Arg103Trp). They were identified with whole-exome sequencing and verified with Sanger sequencing. At 7 years and 9 months, our patient had developed multiple types of seizures, prominent myoclonus with photosensitivity, regression in motor and language skills, pyramidal and extrapyramidal signs, and brain atrophy in brain images, all of which were progressive and were compatible with vLINCLs. However, this first Korean report shows no visual impairment, which resembles the previously reported Japanese case.
Asian Continental Ancestry Group ; Atrophy ; Brain ; Ceroid ; Child ; Female ; Humans ; Lysosomes ; Myoclonic Epilepsies, Progressive* ; Myoclonus ; Neurodegenerative Diseases ; Neuronal Ceroid-Lipofuscinoses ; Neurons ; Seizures ; Vision Disorders

A 20-year-old woman was admitted because of intractable seizures, myoclonus, gait ataxia, and severe intellectual deterioration with age of onset at 16 years. She had no family history of neurological disease. A thorough laboratory investigation was unremarkable. Brain MRI showed generalized cerebral and cerebellar atrophy. Interictal EEG showed intermittent generalized polyspike and waves, maximum on the bilateral parieto-occipital areas, and MNSEP showed giant cortical SEP. Brain biopsy revealed intraneuronal accumulation of granular osmiophilic deposits (GROD), which is characteristic of electromicroscopic findings of neuronal ceroid lipofuscinosis (NCL). We report biopsy-proven adult NCL, which is one of the rare neurodegenerative diseases. (J Korean Neurol Assoc 19(1):45~48, 2001
Adult* ; Age of Onset ; Atrophy ; Biopsy* ; Brain* ; Electroencephalography ; Female ; Gait Ataxia ; Humans ; Magnetic Resonance Imaging ; Myoclonus ; Neurodegenerative Diseases ; Neuronal Ceroid-Lipofuscinoses* ; Neurons* ; Seizures ; Young Adult