Case Of Neuronal Ceroid Lipofuscinosis Research Articles

Clinico- investigative profile of 7 genetically confirmed cases of neuronal ceroid lipofuscinosis: Indian perspective

To describe a cohort of genetically confirmed Neuronal Ceroid Lipofuscinoses (NCL) from a tertiary-care institute from India. A retrospective study on genetically confirmed NCL's (2017–2019). A total of 7 patients were classified into 5 subgroups based on protein and gene defect. CLN7-NCL = 2 patients, mean age of onset 3.5 years, both males, clinically had developmental delay and regression following a febrile illness. One patient had spasmus nutans and bulls eye maculopathy. Homozygous 5′ splice site variation in intron 9, c.863 + 1G > A (5′ splice site) of the MFSD8 gene(chr4:128854139C > T) was detected in one patient and deletion of exon 1 to 3 in MFSD8 gene in the other. CLN6-NCL = 2 patients, mean age of onset 9.5 years, M:F = 1:1, had developmental delay, seizures and progressive extrapyramidal manifestations. Homozygous mutations in CLN6 gene at Exon 4 c.425A > G(p.Tyr142Cys); and Exon 2 c.103G > A(p.Asp35Asn) respectively. CLN1-NCL = 1 patient, age of onset 1.5 years boy, had developmental delay, regression, hypertonia and retinitis pigmentosa. Neuroimaging showed diffuse cortical atrophy. Compound heterozygous mutations in PPT1 gene at Exon 7 c.674 T > C(p.Phe225Ser) and Exon 7 c.651_671 del(p.Asn218_Lys224del) was present. CLN3-NCL = 1, age of onset 8 years, male, had progressive vision loss, cognitive decline with autistic features. Neuroimaging showed cerebellar and cerebral atrophy. Compound heterozygous mutations noted in Intron 9 c.534-2A > G(splice site) and Exon 10 c.565G > T(p.Gly189Trp) of CLN3 gene respectively. CLN8 = 1, age of onset 5 years with regression, cerebellar and visual symptoms, genetically had homozygous mutation in CLN8 gene[c.208C > T(p.Arg70Cys)]. This study describes a cohort of genetically confirmed NCL's from our centre and demonstrates the genetic heterogeneity.

Effectiveness and Adverse Effect of Intravenous Lacosamide in Nonconvulsive Status Epilepticus and Acute Repetitive Seizures in Children.

Nonconvulsive status epilepticus (NCSE) and acute repetitive seizures (ARS) are associated with significant morbidity and mortality. Due to the lack of randomized-controlled trials of intravenous antiepileptic drugs (AEDs) in these conditions, trials of a new generation of AEDs in this aspect are needed. A prospective interventional study was conducted in children under 18 years of age with NCSE or ARS who either had contraindication to or were refractory to first-line AEDs and received intravenous lacosamide. Demographic data, the efficacy of treatment, and adverse effects were recorded. Eleven patients with a median age of 11 years, predominantly female (72.7%), were enrolled. Average loading dose was 227 mg (8.3 mg/kg/dose) and average daily maintenance dose was 249 mg (4.6 mg/kg/dose). All patients (100%) experienced a reduction in seizure frequency within 24 hours. Eight of eleven patients (72.7%) experienced a reduction in seizure frequency of more than 50% by the end of the study, and one patient became seizure-free. In terms of adverse events, one patient had a bradycardia without prolongation of the PR interval. Interestingly, there was a case of neuronal ceroid lipofuscinosis in which a significant improvement in seizure control was achieved. The results indicate that intravenous lacosamide may be an alternative treatment for NCSE or ARS in children. To our knowledge, this is the first study on the use of intravenous lacosamide in Asian children. This study is registered to Thai Clinical Trials Registry (TCTR) and the trial registration number is TCTR20180508004.

Portuguese family with the co-occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation

We and others have reported heterozygous progranulin mutations as an important cause of frontotemporal lobar degeneration (FTLD). It has been identified a complete progranulin deficiency because of a homozygous mutation in a sibling pair with neuronal ceroid lipofuscinosis (NCL). Here, we describe the first case of NCL caused by a homozygous progranulin mutation segregating in a family with neuropathological confirmed FTLD. In this FTLD-NCL family, we detail the clinical phenotype, neuropsychological evaluation and imaging data of our proband harboring a homozygous mutation, c.900_901dupGT, with serum progranulin level (<6 ng/mL). Symptoms included rapidly progressive visual deficit, slightly dysarthria, and cerebellar ataxia. The electroretinogram confirmed a severe attenuation of rod and cone responses compatible with retinal dystrophy diagnosis and magnetic resonance imaging showed severe global cerebellar atrophy. In contrast, heterozygous relatives presented behavioral variant of frontotemporal dementia (FTD) and some also developed extrapyramidal features compatible with corticobasal syndrome. Our findings suggest the importance of assessing serum progranulin levels in suspected recessive adult-onset NCL cases. Overall, a more holistic neurologic intervention is needed to guarantee a proper genetic counseling in cases like the present family where two distinct phenotypes are generated according to the individuals' mutation state.

A Case of Neuronal Ceroid Lipofuscinosis Masquerading as Panayiotopoulos Syndrome

Neuronal ceroid lipofuscinosis (NCL) is probably the most common group of childhood progressive neurodegenerative disorders that typically present in childhood, and are uniformly fatal. We present here an unusual case of NCL based on clinical and electroencephalographic features as well as review the current literature on the early features of NCL. The purpose is to alert physicians about the atypical presentations of NCL encountered in clinical practice and to broaden their differential considerations so that earlier diagnoses can be made. In particular, patients presenting with epilepsy and behavioral problems who show developmental regression warrant further investigation.

PP03.7 – 2754: KCTD7 mutation causing infantile neuronal ceroid lipofucinosis

Objective Neuronal ceroid lipofuscinosis (NCL) is one of the progressive myoclonic epilepsies (PME) of childhood with 14 types currently described. We present a case of NCL with a novel potassium channel tetramerization containing 7 (KCTD7) gene mutations. Case A 10 year old previously well boy presented at 23 months old with rapid onset global regression. Within 6 months he was non-ambulant and had developed generalised dystonia, non-epileptic myoclonus and epilepsy (tonic clonic seizures). Family history was unremarkable. The EEG at 29 months demonstrated a diffuse slow background and frequent independent spike and sharp waves bilaterally. MRI brain (with spectroscopy) was initially normal but at 5 and 7 years showed signal changes in both cerebellar hemispheres with mild global atrophy. Extensive neurometabolic investigations were normal including ultrastructural examination of lymphocytes, white cells and cultured fibroblasts lysosomal enzyme activity, muscle histology and respiratory chain enzymes, electroretinogram and visual evoked potentials were normal. Brain biopsy at 8 years demonstrated membrane-bound lysosomal accumulation of electron dense material in numerous neurons but did not contain curvilinear inclusion material characteristic of NCL. Repeat ultrastructural examination of lymphocytes and white cell enzyme activity was again normal. Results Genetic testing by next-generation sequencing, through DDD study, revealed autosomal recessive compound heterozygote mutations in KCTD7 gene exon 2 (c.190A>G, p. Thr64Ala) and 4 (c.631C>T, p.Arg211X). This was confirmed by DNA sequence analysis. The KCTD7 gene has recently been associated with infantile-onset NCL subtype CLN14 and PME type 3 (EPM3). Conclusion KCTD7 mutation testing should be considered in children with suspected infantile NCL when first line diagnostic tests are normal.

Juvenile neuronal ceroid-lipofuscinosis with hypertrophic cardiomyopathy and left ventricular noncompaction: a case report.

We report a 17-year-old female with juvenile neuronal ceroid-lipofuscinosis (NCL) accompanied by hypertrophic cardiomyopathy (HCM) and left ventricular noncompaction (LVNC). Within our knowledge, this is the first reported case of juvenile NCL with LVNC, and the youngest case of HCM diagnosed by ultrasound. Juvenile NCL is a progressive hereditary disease involving multi-organ accumulation of ceroid-lipofuscin; its resulting complications require prompt attention. Due to its relative rarity, its cardiac involvement is not well known. Based on findings from this patient and related juvenile NCL cases, the risk of cardiac involvement tends to increase with age; a high frequency of ventricular hypertrophy has been reported in patients aged older than 20 years of age. Medical progress and comprehensive care have led to longer survival in patients with juvenile NCL, which likely increases the incidence of cardiac involvement. In relation to HCM in other metabolic disorders, attention should be paid to arrhythmias, including repolarization disturbances, sinus node dysfunction and ventricular tachycardia. LVNC is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intratrabecular recesses, which are associated with diastolic or systolic dysfunction, thromboembolic complications and arrhythmias. From ours and other case reports, we recommend regular follow-up of NCL patients as follows: echocardiography to estimate cardiomyopathy, Holter monitoring to identify arrhythmias, and computed tomography to detect thrombosis from both ventricles. The mechanism of the HCM and LVNC associated with juvenile NCL remains unclear. Our case requires careful follow-up. Prospective studies of the cardiac involvement in juvenile NCL are necessary to further elucidate its pathomechanism.

初期の臨床症状として視覚障害を呈した神経セロイドリポフスチン症のチワワの1例

初期の臨床症状として視覚障害を呈した神経セロイドリポフスチン症のチワワの1例

肥大型心筋症と左室緻密化障害が判明した若年型neuronal ceroid-lipofuscinosisの1例

We report a 17-year-old female with juvenile neuronal ceroid-lipofuscinosis (NCL) accompanied by hypertrophic cardiomyopathy (HCM) and left ventricular noncompaction (LVNC). Within our knowledge, this is the first reported case of juvenile NCL with LVNC, and the youngest case of HCM diagnosed by ultrasound. Juvenile NCL is a progressive hereditary disease involving multi-organ accumulation of ceroid-lipofuscin; its resulting complications require prompt attention. Due to its relative rarity, its cardiac involvement is not well known. Based on findings from this patient and related juvenile NCL cases, the risk of cardiac involvement tends to increase with age; a high frequency of ventricular hypertrophy has been reported in patients aged older than 20 years of age. Medical progress and comprehensive care have led to longer survival in patients with juvenile NCL, which likely increases the incidence of cardiac involvement. In relation to HCM in other metabolic disorders, attention should be paid to arrhythmias, including repolarization disturbances, sinus node dysfunction and ventricular tachycardia. LVNC is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intratrabecular recesses, which are associated with diastolic or systolic dysfunction, thromboembolic complications and arrhythmias. From ours and other case reports, we recommend regular follow-up of NCL patients as follows: echocardiography to estimate cardiomyopathy, Holter monitoring to identify arrhythmias, and computed tomography to detect thrombosis from both ventricles. The mechanism of the HCM and LVNC associated with juvenile NCL remains unclear. Our case requires careful follow-up. Prospective studies of the cardiac involvement in juvenile NCL are necessary to further elucidate its pathomechanism.

An atypical case of neuronal ceroid lipofuscinosis with co-inheritance of a variably penetrant POLG1mutation

BackgroundThe neuronal ceroid lipofuscinoses (NCLs, or Batten disease) comprise the most common Mendelian form of childhood-onset neurodegeneration, but the functions of the known underlying gene products remain poorly understood. The clinical heterogeneity of these disorders may shed light on genetic interactors that modify disease onset and progression.Case presentationWe describe a proband with congenital hypotonia and an atypical form of infantile-onset, biopsy-proven NCL. Pathologic and molecular work-up of this patient identified CLN5 mutations as well as a mutation―previously described as incompletely penetrant or a variant of unknown significance―in POLG1, a nuclear gene essential for maintenance of mitochondrial DNA (mtDNA) copy number. The congenital presentation of this patient is far earlier than that described for either CLN5 patients or affected carriers of the POLG1 variant (c.1550 G > T, p.Gly517Val). Assessment of relative mtDNA copy number and mitochondrial membrane potential in the proband and control subjects suggested a pathogenic effect of the POLG1 change as well as a possible functional interaction with CLN5 mutations.ConclusionsThese findings suggest that an incompletely penetrant variant in POLG1 may modify the clinical phenotype in a case of CLN5 and are consistent with emerging evidence of interactions between NCL-related genes and mitochondrial physiology.

Mutational analysis of the feline CLN3 gene and an ultrastructural evaluation of lysosomal storage materials in a cat with neuronal ceroid lipofuscinosis: An investigation into the molecular basis of the disease

Neuronal ceroid lipofuscinosis (NCL) is a neurodegenerative disease caused by a number of different genes. A mutational analysis of the feline CLN3 gene was performed in a cat with NCL that had vacuolated lymphocytes, which is a feature of human NCL caused by defects of the CLN3 gene. To determine the candidate gene(s) responsible for this case, NCL-specific ultrastructures of storage materials were analysed. A sequence analysis indicated that the CLN3 gene was not likely to be responsible for this case of feline NCL because no deleterious mutation was detected. An ultrastructural analysis did not reveal any candidate gene because of inconsistency with any pattern found in human NCL. These findings suggest that the diagnostic criteria for human NCL are not directly applicable to feline NCL.

A One Base Pair Deletion in the Canine ATP13A2 Gene Causes Exon Skipping and Late-Onset Neuronal Ceroid Lipofuscinosis in the Tibetan Terrier

Neuronal ceroid lipofuscinosis (NCL) is a progressive neurodegenerative disease characterized by brain and retinal atrophy and the intracellular accumulation of autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and other cells. Tibetan terriers show a late-onset lethal form of NCL manifesting first visible signs at 5–7 years of age. Genome-wide association analyses for 12 Tibetan-terrier-NCL-cases and 7 Tibetan-terrier controls using the 127K canine Affymetrix SNP chip and mixed model analysis mapped NCL to dog chromosome (CFA) 2 at 83.71–84.72 Mb. Multipoint linkage and association analyses in 376 Tibetan terriers confirmed this genomic region on CFA2. A mutation analysis for 14 positional candidate genes in two NCL-cases and one control revealed a strongly associated single nucleotide polymorphism (SNP) in the MAPK PM20/PM21 gene and a perfectly with NCL associated single base pair deletion (c.1620delG) within exon 16 of the ATP13A2 gene. The c.1620delG mutation in ATP13A2 causes skipping of exon 16 presumably due to a broken exonic splicing enhancer motif. As a result of this mutation, ATP13A2 lacks 69 amino acids. All known 24 NCL cases were homozygous for this deletion and all obligate 35 NCL-carriers were heterozygous. In a sample of 144 dogs from eleven other breeds, the c.1620delG mutation could not be found. Knowledge of the causative mutation for late-onset NCL in Tibetan terrier allows genetic testing of these dogs to avoid matings of carrier animals. ATP13A2 mutations have been described in familial Parkinson syndrome (PARK9). Tibetan terriers with these mutations provide a valuable model for a PARK9-linked disease and possibly for manganese toxicity in synucleinopathies.

Intraventricular Enzyme Replacement Improves Disease Phenotypes in a Mouse Model of Late Infantile Neuronal Ceroid Lipofuscinosis

Late infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive neurodegenerative disease caused by mutations in CLN2, which encodes the lysosomal protease tripeptidyl peptidase 1 (TPP1). LINCL is characterized clinically by progressive motor and cognitive decline, and premature death. Enzyme-replacement therapy (ERT) is currently available for lysosomal storage diseases affecting peripheral tissues, but has not been used in patients with central nervous system (CNS) involvement. Enzyme delivery through the cerebrospinal fluid is a potential alternative route to the CNS, but has not been studied for LINCL. In this study, we identified relevant neuropathological and behavioral hallmarks of disease in a mouse model of LINCL and correlated those findings with tissues from LINCL patients. Subsequently, we tested if intraventricular delivery of TPP1 to the LINCL mouse was efficacious. We found that infusion of recombinant human TPP1 through an intraventricular cannula led to enzyme distribution in several regions of the brain of treated mice. In vitro activity assays confirm increased TPP1 activity throughout the rostral-caudal extent of the brain. Importantly, treated mice showed attenuated neuropathology, and decreased resting tremor relative to vehicle-treated mice. This data demonstrates that intraventricular enzyme delivery to the CNS is feasible and may be of therapeutic value.

Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis

Congenital neuronal ceroid-lipofuscinosis (NCL) is a devastating inherited neurodegenerative disorder of unknown metabolic basis. Eight patients with this rare disorder, all with similar clinical and neuropathological findings, have been reported, and here we describe two further patients. Previously, we showed that a mutation in the cathepsin D gene causes congenital NCL in sheep. On the basis of the neuropathological and ultrastructural similarities between the sheep and patients affected with congenital NCL, we screened the cathepsin D gene for mutations in a patient of Pakistani origin. We identified a nucleotide duplication, c.764dupA, in the cathepsin D gene in homozygous form in the patient, and in heterozygous form in his father. This duplication is likely to be disease-causing, as it creates a premature stop codon, predicting a truncation of the protein. When transiently expressed in cell cultures, the mutant protein was enzymatically inactive, but stable. In paraffin-embedded brain tissue samples of two affected siblings of the Pakistani patient, cathepsin D was absent, suggesting rapid degradation of the c.764dupA mutant cathepsin D at mRNA or protein level in vivo. Further, we were able to confirm lack of cathepsin D in the brain tissue of yet another, unrelated, patient of English origin with congenital NCL. On the basis of the present data, and the nearly identical clinical and/or pathological phenotype of the other reported cases of congenital NCL, it is reasonable to suggest that cathepsin D deficiency caused by mutations in the corresponding gene may underlie all cases of congenital NCL. The present observations also suggest that cathepsin D deficiency should be considered as a possible diagnosis in microcephalic neonates, who present with seizures at or before birth.

Neuronal ceroid lipofuscinoses: clinical and EEG findings in a large study of Italian cases.

We reviewed the clinical and EEG features of 30 Italian patients with childhood-onset neuronal ceroid lipofuscinosis (NCL). The outcome and the EEG pattern of the 4 infantile NCL cases were classic, although the age at onset of symptoms varied from 1.0 to 3.5 years. This latter finding is unusual and has not been reported for other Italian patients. Both typical and variant cases of late-infantile NCL (LINCL) were observed. This NCL type represents the most common form in our country, and was the largest group (18 cases) in our study. A particular pseudoperiodic EEG pattern was observed in 15 of the 18 patients with LINCL. This pattern may be useful in early diagnosis, especially if associated with the absence of sleep spindles. In the 8 cases with juvenile NCL, clinical and EEG findings were similar to those reported in the literature.

Clinical and Molecular Analysis of Japanese Patients with Neuronal Ceroid Lipofuscinosis

Neuronal ceroid lipofuscinosis (NCL) is one of the most common inherited neurological diseases in childhood. It occurs every 12,500 births in northern-European populations. Mental retardation, visual impairment, and seizures are common symptoms. The prevalence of NCL is variable depending upon the races or countries. Although a wealth information is available in Caucasian populations, there is little information about NCL in Asian people. Because a nationwide survey in Japanese patients with NCL has never been performed, we pursued an epidemiological survey. We identified 36 NCL patients in Japan. Patients with infantile, late infantile, juvenile, and adult type accounted for 2, 15, 15, and 4 cases, respectively. Seizures were a major initial symptom in the late infantile type. In the juvenile type, visual failure was present in 73% at onset. Recently, the juvenile NCL (Batten disease) gene has been isolated. Studies of the mutations in this gene demonstrated that a 1.02-kb deletion was the most prevalent mutation among Caucasian patients, accounting for 81% of total alleles. To determine the prevalence of this 1.02-kb deletion in Japanese patients, we performed a rapid allele-specific polymerase chain reaction test. No 1.02-kb major deletion was detected in 5 Japanese juvenile NCL cases. These data suggest that the distribution of NCL and clinical findings are similar to those of Caucasian subjects; however, prevalence of mutations in Japanese patients with NCL would be distinct from that observed in Caucasians.

Electron microscopy study in neurodegenerative diseases in childhood

Neurodegenerative diseases are a group of disorders in which there is storage of abnormal material in cells throughout the body due to an enzyme defect. The authors present the experience in the diagnosis of the neurodegenerative diseases in infancy by electron microscopical study of skin, conjunctival and rectum material of 89 patients and 2 necropsy cases. The age of the patients ranged from 49 days to 13 years with speak age of incidence in first year of life (n = 28). Fifty patients were female and 39 were male. The most frequent sites of biopsy were the skin and conjunctival. Of the total 89 patients, 15 had a definitive diagnosis (16.8%) including 4 cases of gangliosidosis, 3 cases of mucopolysaccharidosis, a case of Gaucher's disease, a case of Niemann-Pick disease, 3 cases of neuronal ceroid lipofuscinosis and 3 cases of storage disease which could not be specified. The authors studied all these patients within clinic and ultrastructural aspects and concluded that electron microscopy is an important method in diagnosis of storage diseases but with a low sensitivity as a single "screening" test for patients with progressive encephalopathy.

Variability in the clinical and pathological findings in the neuronal ceroid lipofuscinoses: review of data and observations.

We reviewed the clinical and pathological data on 319 neuronal ceroid lipofuscinosis (NCL) cases to determine the degree of variability within the different forms and among and within families. Thirty-six cases (11.3%) were the infantile form; 116 cases (36.3%), late infantile; 163 cases (51.1%), juvenile; and four cases (1.3%), the adult form (Kufs disease). Clinical variability was found in all forms studied, but was most striking in the juvenile and late infantile forms of NCL. The expected initial findings of seizures, dementia, blindness, or motor impairment were evident in 255 cases (80%), and rarer, less typical initial neurological symptoms were seen mainly in the 64 cases (20%) of the juvenile form: behavior abnormalities (18/64), psychoses (12/64), neuropathy (2/64), involuntary movements (15/64), ataxia (9/64). Six juvenile and two adult cases had no detectable impairment of vision. All 319 NCL cases had skin or conjunctive biopsies or buffy coats that showed the characteristic ultrastructural abnormalities of NCL. Variability was evident in 16.7% in that a combination of fingerprint, curvilinear, and membranous profile inclusion bodies was observed in storage lysosomes, although one type of inclusion was distinctly predominant for each form. Postmortem examination of brains of 19 NCL cases (three with the infantile form, six with the late infantile form, nine with the juvenile form, and one with the adult form) revealed characteristic changes. Sixteen of the 19 NCL brains (84%) showed pathological variability in that they contained more than one kind of characteristic inclusion body in the neuronal lysosomal storage compartment. In all 19 NCL brains, small amounts of aging lipofuscin were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered amyloid β-protein precursor processing in brains of patients with neuronal ceroid lipofuscinosis

Our previous study disclosed strong immunostaining of brain tissue in neuronal ceroid lipofuscinosis (NCL) with antibodies against amyloid β-protein and the presence of 31-kDa polypeptide in the storage material. In the present study, we investigated the immunoreactivity of the NCL brain tissue with anti-serum (anti-GID) raised against a synthetic peptide, based on the amyloid β-protein precursor, with the 175–186 amino acid sequence. Immunocytochemistry was performed on autopsy brain material collected from 15 NCL cases, and from 8 age-matched normal controls. The results showed strong immunoreactivity of nerve cells in the NCL cases, which according to densitometry was 5 times more intense than in the control group ( P < 0.0001 by Student's t-test). Western blot analysis revealed that in protein fractions of NCL brain homogenates anti-GID recognized the protein band of 35 kDa. Thus, our present and previously performed studies supplied for the first time data pointing to abnormal processing of amyloid β-protein precursor in NCL. Moreover, the accumulation of both 31- and 35-kDa polypeptides that was demonstrated provides further support for postulated defective protein metabolism in this disorder.

Proteinase inhibitor α1-antichymotrypsin has different expression in various forms of neuronal ceroid lipofuscinosis

Defective proteolytic degradation is most widely maintained as the major pathogenetic factor in neuronal ceroid lipofuscinosis (NCL). The goal of the present study was to examine the expression in NCL brain tissue of one of the serine proteinase inhibitors, α 1-antichymotrypsin. Our study was based on previous findings of α 1-antichymotrypsin association with CNS amyloidoses related to amyloid β protein deposits and our previous findings suggesting abnormal processing of amyloid β-protein precursor (ABPP) in NCL brains. Immunocytochemical study was performed on formalin-fixed brain tissues collected from 15 NCL cases representing four different forms of the disorder and from 16 control cases comprising age-matched controls, older nondemented individuals, and Alzheimer disease cases. Our present study has shown that the expression of α 1-antichymotrypsin is generally higher in NCL cases than in control cases; however, it manifests in distinct variations of intensity and proportions of immunostained cells. The strongest immunoreactivity was found in the infantile form of NCL, which is characterized by a rapid clinical course and widespread tissue damage. We found no evidence of direct involvement of α 1-antichymotrypsin in either the ceroid lipopigment accumulation or the abnormal processing of ABPP in NCL. However, our findings may reflect the heterogeneity of the pathomechanism underlying this group of disorders and suggest that, similarly to blood circulation, α 1-antichymotrypsin can also represent an acute-phase protein in brain tissue.

Ceroid-lipofuscinosis: ultrastructural study of 8 cases

The authors studied the clinical and ultrastructural features of 8 cases of Neuronal Ceroid-Lipofuscinosis (NCL). Five cases of the late-infantile type and 3 cases of the juvenile type. The clinical diagnosis of all cases was confirmed by the electron microscopy analysis of the peripheral blood lymphocytes and biopsy material from the skin, palpebral conjunctiva, skeletal muscle and rectal mucosa. Our observations agree with previous reports concerning the predominance of curvilinear bodies in the cells of the late infantile type, and fingerprint-like structures in those of the juvenile type. The finding of parallel tubular arrays and NCL inclusions associated in the same lymphocyte (frequently in the same vacuole) suggests that those structures could be related to the metabolic error of NCL. Ultrastructural examination of microbuffycoats of peripheric blood lymphocytes is a simple, time-saving and reliable method that allows specific confirmation of a clinical diagnosis of Neuronal Ceroid-Lipofuscinosis.