Expert Recommendations for the Laboratory Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2 disease): Diagnostic Algorithm and Best Practice Guidelines for a Timely Diagnosis
Leigh Syndrome is a fatal mitochondrial disease with variable ophthalmologic manifestations. Ptosis can be the initial sign in patients with this rare inherited neurometabolic disorder. Misdiagnosis of conditions including juvenile myasthenia gravis and congenital ptosis delay proper identification and palliative care. We present a noteworthy case of a 16-month-old girl with acquired progressive bilateral ptosis who was diagnosed with Leigh Syndrome after further work up suggested by our examination.
Neuronal Ceriod Lipofuscinosis-2 (CLN) disorder, a type of Batten disease caused by TPP1 enzyme deficiency: Current knowledge of the natural history from international experts
Expert Recommendations for the Laboratory Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2 disease): Diagnostic Algorithm and Best Practice Guidelines for a Timely Diagnosis
Leigh Syndrome is a fatal mitochondrial disease with variable ophthalmologic manifestations. Ptosis can be the initial sign in patients with this rare inherited neurometabolic disorder. Misdiagnosis of conditions including juvenile myasthenia gravis and congenital ptosis delay proper identification and palliative care. We present a noteworthy case of a 16-month-old girl with acquired progressive bilateral ptosis who was diagnosed with Leigh Syndrome after further work up suggested by our examination.
Neuronal Ceriod Lipofuscinosis-2 (CLN) disorder, a type of Batten disease caused by TPP1 enzyme deficiency: Current knowledge of the natural history from international experts
Trials in secondary progressive multiple sclerosis: design & efficiencyMS Trust
This presentation by Dr Jeremy Chataway looks at:
- What is MS progression?
- How would an anti-progressive drug be found?
- What outcome would be measured?
- What trial design could/would be used?
- Where are we now?
It was presented at the MS Trust Annual Conference in November 2013.
A 40-year-old unmarried female presented with abnormal involuntary choreo-athetoid movements involving both upper limbs for 5 years along with features, such as bouts of disorientation, anxiety, personality changes, reckless behaviour, inappropriate laughter and progressive decline in the neurological status. On neurological examination, her speech was dysarthric with mild choreiform movements involving both upper limbs. She had MMSE score of 20/30. MRI scans of the brain plain T1- and T2-weighted axial and flair coronal images were obtained. It showed calcifications as hyper-intense lesions on T1W and hypo-intense T2W lesions in bilateral basal ganglion and bilateral dentate nuclei of cerebellum, that is consistent with Fahr's syndrome.
LGS Foundation 2016 Conference - Friday AfternoonLGS Foundation
Topics include: Understanding Cognitive Problems in LGS presented by Michael Chez, MD, Effective Communication presented by Patricia Moore and, National Resources for Individuals with LGS presented by Jennifer Wolfenbarger, MPH
Abstract—Hutchinson–Gilford Progeria Syndrome is a rare genetic disorder characterized by premature aging involving the skin, bones, heart, and blood vessels. We report a five year old female child with clinical manifestations characteristic of this syndrome. This child had a senile look with large cranium, frontal bossing, sparse light brown hair and dilated visible veins over the scalp. Other features were prominent eyes, beaked nose, micrognathia, sclerodermatous changes in both feet and legs, laxed and atrophic skin over dorsum of both hands and mottled pigmentation over trunk. Decreased high-density lipoprotein (HDL) levels was characteristic of the syndrome. This case is reported for its rarity and uncommon relationship with hypothyroidism.
Trials in secondary progressive multiple sclerosis: design & efficiencyMS Trust
This presentation by Dr Jeremy Chataway looks at:
- What is MS progression?
- How would an anti-progressive drug be found?
- What outcome would be measured?
- What trial design could/would be used?
- Where are we now?
It was presented at the MS Trust Annual Conference in November 2013.
A 40-year-old unmarried female presented with abnormal involuntary choreo-athetoid movements involving both upper limbs for 5 years along with features, such as bouts of disorientation, anxiety, personality changes, reckless behaviour, inappropriate laughter and progressive decline in the neurological status. On neurological examination, her speech was dysarthric with mild choreiform movements involving both upper limbs. She had MMSE score of 20/30. MRI scans of the brain plain T1- and T2-weighted axial and flair coronal images were obtained. It showed calcifications as hyper-intense lesions on T1W and hypo-intense T2W lesions in bilateral basal ganglion and bilateral dentate nuclei of cerebellum, that is consistent with Fahr's syndrome.
LGS Foundation 2016 Conference - Friday AfternoonLGS Foundation
Topics include: Understanding Cognitive Problems in LGS presented by Michael Chez, MD, Effective Communication presented by Patricia Moore and, National Resources for Individuals with LGS presented by Jennifer Wolfenbarger, MPH
Abstract—Hutchinson–Gilford Progeria Syndrome is a rare genetic disorder characterized by premature aging involving the skin, bones, heart, and blood vessels. We report a five year old female child with clinical manifestations characteristic of this syndrome. This child had a senile look with large cranium, frontal bossing, sparse light brown hair and dilated visible veins over the scalp. Other features were prominent eyes, beaked nose, micrognathia, sclerodermatous changes in both feet and legs, laxed and atrophic skin over dorsum of both hands and mottled pigmentation over trunk. Decreased high-density lipoprotein (HDL) levels was characteristic of the syndrome. This case is reported for its rarity and uncommon relationship with hypothyroidism.
Epilepsy is a chronic neurological disorder which is caused by various factors which may vary according to the age of patients which results in asynchronization of neurons. Cognitive functional impairment is mostly seen in epileptic patients compared to the general population, and the degree of its impairment varies from one another according to the epilepsy syndrome. Behavioral changes are more seen in epileptic people and people with drug-resistant epilepsy, frequent seizures, and associated neurological or mental abnormalities. In children and adults, many data suggest a correlation between behavior/cognition and some other specific epilepsy syndromes. The major predictors of such behavioral changes in children with epilepsy are epilepsy itself, treatment, the underlying structural lesion, and epilepsy treatment.
Suac Syndrome is an autoimmune endotheliopathy with about 304 cases described until 2013. It charaterized by the triad of E-H-V (Encephalopathy, Hearing loss and Vision - branch retinal artery occlusions/BRAO [3]. The case report early-onset autoimmune neuropsychiatric disorder in a pre-pubertal 12 year old girl innitialy presenting with behavioral and emotional manifestations
President of MSSA Prof. Dr. Vladimir Trajkovski prsented the his topic: "Association between cerebral palsy and autism spectrum disorders" at 8th interdisciplinary congress: "Cerebral palsy and other movement disorders" on 1-2 of November 2018 in Moscow, Russia.
A case of Neuromyelitis optica as a presenting manifestation of Systemic Lupu...Apollo Hospitals
Neuromyelitis optica (NMO) is a well characterised, autoimmune, clinicopathological syndrome, which is uncommon and occurs as an isolated entity. Unlike multiple sclerosis, in NMO, the autoimmunity is humorally mediated and the recent availability of Antiaquaporin antibody testing has increased the positive diagnosis of this condition. NMO can also occur in patients with established Systemic Lupus Erythematosis (SLE) who have multiple autoantibodies. The presence of Antiaquaporin antibody is specific for NMO and is seen in patients with SLE who develop inflammatory CNS disease. However, Neuromyelitis optica occurring as a presenting manifestation of SLE is extremely rare and we report one such case.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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2018 BDSRA Gayko
1. A literature review focused on childhood onset NCL Childhood
onset NCL
subtypes
Early signs and symptoms of Neuronal Ceroid Lipofuscinosis (NCL)
Alanna Gayko, MEd, (MPhil Candidature); Dr Elizabeth Kepreotes PhD; Dr Tracy Dudding-Byth BMed, FRACP, PhD; Professor Vanessa McDonald PhD
Faculty of Health and Medicine, School of Nursing and Midwifery, University of Newcastle, Australia
INTRODUCTION
Delayed or initial misdiagnosis of NCL (Batten disease) is
experienced by many families. NCL affects all age groups, but
predominantly young children.
AIM
Our aim was to undertake a comprehensive literature review to
establish the known early signs and symptoms of childhood onset
NCL. The focus was on the early pre-diagnostic phase.
METHOD
The PubMed® database was searched for articles which referred
to early symptoms of any subtype of NCL. The MESH terms
‘Neuronal Ceroid Lipofuscinosis’ AND ‘symptoms’ were used.
Google Scholar was manually searched using the eponym Batten
disease and the CLN1-14 subtypes.
1,193 articles were identified during this review completed on June
30th, 2018. Duplicates and articles not specifying early onset NCL
symptoms in childhood were excluded. This is an excerpt of the
130 historical and recent articles included in the literature review.
RESULTS
From the literature review we identified symptoms specific to each
subtype and the age of onset. Factors are identifiable which
facilitate or delay diagnosis of childhood onset NCL.
Paramount symptoms: NCL is the leading life-limiting Mendelian
cause of neurodegeneration and dementia in children [2]. Stalling
and regression of psychomotor abilities in a young child is the broad
symptom heralding the onset of dementia requiring consideration of
NCL. Symptoms such as speech delay or regression, ataxia, onset
of seizures, and visual loss are characteristic of specific subtypes. A
child has usually achieved normal developmental milestones [3].
Age of onset: With exceptions of later onset phenotypes and rarer
subtypes, the age of childhood onset NCL subtypes is narrow. The
earliest onset subtypes are congenital-CLN10 (perinatal to
postnatal) and during infancy-CLN1 (six months to two years).
Children have an onset in the late infantile period-CLN2 (two to four
years). Slightly older children with the juvenile onset-CNL3 become
symptomatic (between four and seven years, or later) [3, 18].
Variants CLN5-CLN8 may present at two to five years or older [6-9].
Health professionals: Speech pathologists (CLN2) [19] and
ophthalmologists (CLN3) [20] may review these children in the early
symptomatic, but pre-diagnostic phase of NCL. Tailoring education
and awareness of NCL can reduce time to diagnosis of NCL [21].
Differential diagnosis: CLN2 may be initially misdiagnosed as
epilepsy syndromes [4]. Initial ophthalmology misdiagnoses are
common for several subtypes, but particularly CLN3 [20, 22].
Benefits of early diagnosis: To end a protracted diagnostic
journey, sometimes referred to as a ‘diagnostic odyssey’ in rare
disease literature. Delayed diagnosis may be:
• ˃ 21 months for CLN2, late-infantile [3-4]
• ˃ two years for CNL3, juvenile [5]
Emerging treatments: Early diagnosis of NCL may facilitate
participation in a clinical trial [23]. It could expedite access to the
first disease modifying treatment for children with a genetic
diagnosis of CLN2 [24] or other emerging treatments [25].
CONCLUSION
NCL is typified by misdiagnosis or a delayed diagnosis. Identifying
dementia in childhood is protracted as symptoms merge with more
common or other rare diseases. The interval from subtle symptoms
- a prodromal phase - before overt symptoms and diagnosis may
illuminate the onset of NCL. Parents are well equipped to identify
distinctive features of this pre-diagnostic period in their child or
children. Symptom onset and the diagnostic experience of families
will be retrospectively explored in a forthcoming Australian study.
References:
1. van Ruiten, H.J., et al., Improving recognition of Duchenne muscular dystrophy: a retrospective case note review. Archives of disease in childhood, 2014. 99(12): p. 1074-1077.
2. Schulz, A. and A. Kohlschutter, NCL Disorders: frequent causes of childhood dementia. Iranian journal of child neurology, 2013. 7(1): p. 1-8.
3. Williams, R.E., et al., Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochim Biophys Acta, 2006. 1762(10): p. 865-72.
4. Fietz, M .., et al., Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Molecular Genetics and Metabolism, 2016. 119(1): p. 160-167.
5. Adams, H.R., J.W. Mink, and the University of Rochester Batten Center Study Group, Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). J Child Neurol, 2013. 28(9): p. 1128-36.
6. Simonati, A., et al., Phenotype and natural history of variant late infantile ceroid-lipofuscinosis 5. Dev Med Child Neurol, 2017. 59(8): p. 815-821.
7. Canafoglia, L., et al., Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations. Neurology, 2015. 85(4): p. 316-324.
8. Aiello, C., et al., Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis. Hum Mutat, 2009. 30(3): p. E530-40.
9. Striano, P., et al., Clinical and electrophysiological features of epilepsy in Italian patients with CLN8 mutations. Epilepsy Behav, 2007. 10(1): p. 187-91.
10. Santavuori, P., S.-L. Vanhanen, and T. Autti, Clinical and neuroradiological diagnostic aspects of neuronal ceroid lipofuscinoses disorders. European Journal of Paediatric Neurology, 2001. 5: p. 157-161.
11. Williams, R.E., S. Boyd, and B.D. Lake, Ultrastructural and electrophysiological correlation of the genotypes of NCL. Molecular genetics and metabolism, 1999. 66(4): p. 398-400.
12. Siintola, E., et al., Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain, 2006. 129(6): p. 1438-1445.
Acknowledgements: This research is partly supported by an Australian Government Research Training Program Scholarship
The most common age of childhood onset subtypes is between two and five years [2-9] as provided in
Figure 1. CLN1 has an infantile onset between 6 months to two years [10] and CLN10 has a
congenital onset [12], or later.
Figure 1: Ages of neonatal and childhood onset subtypes CLN 10, 1-3 and 5-8
RESULTS
Early signs and symptoms of childhood onset NCL subtypes were
identified in the literature. The mnemonic NEURONS has been
used [1], to summarise the distinctive features of these NCL
subtypes. Table 1 below focuses on the earliest symptoms of
neurological standstill, then regression in a young infant or child.
These can range from subtle to obvious changes to speech, gait
(ataxia), and behaviour prior to seizures (CLN2), visual loss
(CLN3) [2-5] and initial symptoms of other subtypes [6-10].
Enlarged organs (organomegaly) or distinctive facial features
(dysmorphia) are not characteristic of early NCL [15,4].
Ultrastructural pathology is distinctive to NCL, but vacuolated
lymphocytes identified in CLN3 are also found in other lysosomal
diseases [15].
Table 1: Distinctive features of childhood onset NCL
phenotypes of CLN1-3 [2-5], CLN5-8 [6-10]
Facilitators and hindrances of NCL diagnosis are
outlined in the adjoining Figure 2.
Facilitators of diagnosis:
1. Parents (and others) may identify early subtle
symptoms in their child or children [13]
2. Consideration of NCL by the medical
practitioner (and other professionals) [4, 14]
3. Family and medical history → referral [4, 22]
Hindrances of diagnosis:
4. Lack of awareness of NCL [2, 21]
5. Subtle symptoms prior to motor or visual ↓ [16]
6. No facial dysmorphia or organomegaly [4, 15]
7. Differential diagnoses: Rett syndrome CLN1, 2
[10], retinitis pigmentosa CLN3 [22]
Figure 2: Facilitators and hindrances of
NCL diagnosis
The earliest symptoms of the CLN1-CLN3 subtypes are provided in Figure 3 [4-5, 10, 16-17]. Speech
delay/regression can be identified early in CLN5-CLN6 [6-7], and clumsiness at the onset of CLN5 [6].
Figure 3: Early presentation of childhood onset phenotypes of CLN1-CLN3
Signs & symptoms of childhood onset NCL Subtypes
1. N: Neurological standstill CLN1, 2
2. E: Epilepsy - Tonic-clonic, myoclonus CLN2, 7, 8
3. U: Ultrastructural pathology, autofluorescence All subtypes [11]
4. R: Regression - motor/cognitive, dementia CLN1, 2, 3
5. O: Ophthalmic - retinopathy, vision loss CLN3
6. N: New onset ataxia CLN1, 2, 6
7. S: Speech delay CLN1, 2, 5, 6
13. Pampiglione, G. and A. Harden, So-called neuronal lipofuscinosis. Neurological studies in 60 children. Journal of Neurology, Neurosurgery, and Psychiatry., 1977. 40: p. 323-330.
14. Puga, A.C.S., et al., Neuronal ceroid lipofuscinoses: a clinical and morphological study of 17 patients from southern Brazil. Arquivos de neuro-psiquiatria, 2000. 58(3A): p. 597-606.
15. Gilbert-Barness, E. and P.M. Farrell, Approach to diagnosis of metabolic diseases. Translational Science of Rare Diseases, 2016. 1(1): p. 3-22.
16. Kuper, W.F., et al., Timing of cognitive decline in CLN3 disease. Journal of inherited metabolic disease, 2018: p. 1-5.
17. Nickel, M., A. Kohlschütter, and A. Schulz, Late Talkers in Late Infantile CLN2 Disease: Red Flag for an Early Diagnosis. Neuropediatrics, 2015. 46(S 01): p. PS01-20.
18. Nita, D.A., S.E. Mole, and B.A. Minassian, Neuronal ceroid lipofuscinoses. Epileptic Disord, 2016. 18(S2): p. 73-88.
19. Mole, S.E., R.E. Williams, and H.H. Goebel, Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics, 2005. 6(3): p. 107-126.
20. Dulz, S., et al., Novel morphological macular findings in juvenile CLN3 disease. Br J Ophthalmol, 2016. 100(6): p. 824-8.
21. Cismondi, I.A., et al., Guidelines for incorporating scientific knowledge and practice on rare diseases into higher education: neuronal ceroid lipofuscinoses as a model disorder. Biochim Biophys Acta, 2015. 1852(10 Pt B): p. 2316-23.
22. Collins, J., et al., Batten disease: features to facilitate early diagnosis. Br J Ophthalmol, 2006. 90(9): p. 1119-24.
23. Velinov, M., Neuronal Ceroid Lipofuscinoses: Why early diagnosis matters? Ann Pediatr Child Health, 2014. 2(2)(1016): p. 1-3.
24. Schulz, A., et al., Long-term safety and efficacy of intracerebroventricular enzyme replacement therapy with cerliponase alfa in children with CLN2 disease: Two year results from an ongoing multicenter extension study.
Molecular Genetics and Metabolism, 2018. 123(2): p. S126-S127.
25. www.clinicaltrials.org Accessed on 30th June 2018.