This text brings together leading authorities presenting state-of-the-art clinical reviews covering the science, recognition, and treatment of the inherited metabolic epilepsies and related disorders. [books.google.com]

The median age at presentation was 3 years (range: 1-7 years). Consanguinity was present in seven children and family history of similar illness was present in five patients (45.5%). [neurologyindia.com]

Clinical description The clinical presentation varies widely between forms but the clinical hallmark is a combination of dementia, visual loss, and epilepsy. [orpha.net]

Results: The present patient was 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. [atm.amegroups.com]

Clinical presentation is heterogeneous as is onset, which renders the diagnosis hard to make. [radiopaedia.org]

• Epilepsy

  […] in metabolic epilepsies. [books.google.com]

  […] lipofuscinosis AD/AR 36 175 KCNC1 Epilepsy, progressive myoclonic AD 5 2 KCTD7 * Epilepsy, progressive myoclonic AR 13 17 MFSD8 Ceroid lipofuscinosis, neuronal AR 25 46 NEU1 Sialidosis AR 22 60 NHLRC1 Epilepsy, progressive myoclonic AR 15 70 POLG POLG-related [blueprintgenetics.com]

  Epilepsy and dementia without visual loss in these patients may be indicative of a form of JNCL known as the Northern epilepsy variant (progressive epilepsy-intellectual deficit, Finnish type; see this term). [orpha.net]

  SLC19A3, SLC2A1, SLC6A1, SLC6A8, SLC9A6, SMC1A, SPATA5, STX1B, SYNGAP1, TBC1D24, TCF4, TPP1, UBE3A, WDR45, ZEB2 Clinical Utility: Molecular confirmation of a clinical diagnosis To assist with decisions about treatment and management of individuals with epilepsy [genedx.com]

• Turkish

  CLN7 The CLN7 gene has been assigned to the Turkish LINCL (tLINCL) variant. Individuals with the tLINCL variant were thought to originate from Turkey. [emedicine.medscape.com]

  CLN7 Patients with CLN7 is a variant of late infantile-onset NCL, known as Turkish NCL due to its initial description in Turkish families [ 26 ]. [omicsonline.org]

  The pathological changes found in the present study on Finnish material have been confirmed by Danis" who studied the autopsy eyes of a small boy of Turkish extraction. [healio.com]

  The genetic variants of LINCL, namely, Finnish, Indian/Gypsy, and Turkish are now called CLN5, CLN6-7, and CLN8, respectively. [2] However, these phenotypes are not exclusive to the respective ethnic groups. [neurologyindia.com]

• Developmental Delay

  Common presenting features included refractory seizures, developmental delay/regression, and abnormal movements. [neurologyindia.com]

  In some NCLs, developmental delay, speech delay, ataxia, cerebellar and cerebral atrophy, hand stereotypies, sleep disturbances, behavioral/psychiatric disturbances, or additional brain MRI findings may develop. [invitae.com]

  The clinical features include visual decline, motor developmental delay, dysarthria, ataxia, and seizures. Seizures are an early feature in CLN6, occurring before 5 years in more than 60% of patients. [omicsonline.org]

  delay due to ALDH6A1 deficiency 289307 Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency 289307 Developmental delay due to MMSDH deficiency 329195 Developmental delay with ASD and gait instability 329195 Developmental delay [doczz.net]

• Wheelchair Bound

  Progressive loss of motor functions (movement and speech) start with clumsiness, stumbling and Parkinson-like symptoms; eventually, those affected become wheelchair-bound, are bedridden, and die prematurely. 1,2 Juvenile Batten disease is one of a group [beyondbatten.org]

• Visual Impairment

  Patients with Batten disease suffer progressive neurological impairment because of their damaged cells. Symptoms like visual impairment and seizures are among the difficulties they will face. [bdsra.org]

  As this happens, the symptoms of CLN2 disease (for example, language development delay, seizures, and visual impairment) appear. 3 BDSRA logo Key sources Kohlschütter A, Schulz A. CLN2 disease (classic late infantile neuronal ceroid lipofuscinosis). [cln2family.com]

  Visual loss occurs but is not obvious because of profound cognitive impairment. [omicsonline.org]

  Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients. Mol Genet Metab. 2019;126(2):188-95. doi: 10.1016/j.ymgme.2018.12.001. [ Links ] 3. [scielo.org.co]

  Most types of NCL, except for the adult form and Northern epilepsy, are associated with visual impairment that often progresses to blindness. [invitae.com]

• Visual Impairment

  Patients with Batten disease suffer progressive neurological impairment because of their damaged cells. Symptoms like visual impairment and seizures are among the difficulties they will face. [bdsra.org]

  As this happens, the symptoms of CLN2 disease (for example, language development delay, seizures, and visual impairment) appear. 3 BDSRA logo Key sources Kohlschütter A, Schulz A. CLN2 disease (classic late infantile neuronal ceroid lipofuscinosis). [cln2family.com]

  Visual loss occurs but is not obvious because of profound cognitive impairment. [omicsonline.org]

  Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients. Mol Genet Metab. 2019;126(2):188-95. doi: 10.1016/j.ymgme.2018.12.001. [ Links ] 3. [scielo.org.co]

  Most types of NCL, except for the adult form and Northern epilepsy, are associated with visual impairment that often progresses to blindness. [invitae.com]

• Ataxia

  These individuals tend to have milder features overall compared to those diagnosed earlier, but with more severe ataxia. [icdlist.com]

  Neurology 54;1676-1680 2000 Acta Neuropathol(Berl) 97;275-278 1999 Research Grants & Projects Periventricular leukomalacia: neuroimaging, neuropathology, and clinical features Neuronal ceroid lipofuscinosis: molecular diagnosis and pathogenesis Ataxia [researchmap.jp]

  Patients may also exhibit cerebellar ataxia, dementia, neuropathy, and myopathy. [blueprintgenetics.com]

  Patients with onset after four years of age have a milder course with more prominent ataxia and less prominent seizures. [omicsonline.org]

  Showing of 11 | 80%-99% of people have these symptoms Abnormal pyramidal sign 0007256 Abnormality of extrapyramidal motor function 0002071 Ataxia 0001251 Dementia Dementia, progressive Progressive dementia [ more ] 0000726 Generalized myoclonic seizures [rarediseases.info.nih.gov]

• Myoclonus

  Various clinical and genetic phenotypes of adult NCL may be recognized, one featuring a progressive myoclonus epilepsy. [karger.com]

  Other features like myoclonus, ataxia and vision loss develop later in the course with optic atrophy being detectable within 2½ years of vision loss. [annalsofian.org]

  As with younger affected children, older individuals develop a decline in intellectual function, myoclonus, epilepsy, and vision loss. [icdlist.com]

  Parasitic Diseases of the Nervous System E-2075 117 Neurologic Complications of Immunization E-2132 118 Paraneoplastic Neurologic Syndromes E-2142 119 ImmuneMediated Epilepsy Movement Disorders and Hashimotos Encephalopathy in Children E-2150 120 Opsoclonus Myoclonus [books.google.com]

  Involuntary movements (ataxia, myoclonus or spastic quadriparesis) occur. Myoclonus may be severe and refractory to medications. Visual loss occurs but is less obvious for the same reason as in CLN1. ERG is effective to evaluate visual acuity. [omicsonline.org]

• Dystonia

  Treatment Treatment Options: Treatment is primarily symptomatic for sleep disorders, seizures, psychoses, malnutrition, dystonia and spasticity. [disorders.eyes.arizona.edu]

  12 3306 Duplication/inversion 15q11 210571 Dystonia 16 97339 Dural sinus malformation 98811 Dystonia 18 1656 Durhing-Brocq disease 256 Dystonia musculorum deformans 98984 Dusty cataract 199351 Dystonia-parkinsonism, Paisan-Ruiz type 3377 Dutch-Kentucky [doczz.net]

  Clinical variability within the families was noticed among two kindred (one had refractory seizures and regression, whereas the other presented with developmental delay and dystonia) in our study. [neurologyindia.com]

  These are dopa-responsive dystonia (DRD; Segawa disease) (Segawa 2011) and sepiapterin reductase (SR) deficiency (Friedman et al. 2012). [pdfcoffee.com]

• Mental Deterioration

  Signs and symptoms include progressive vision loss, progressive motor skills deterioration, mental impairment, and seizures. Infantile neuronal ceroid lipofuscinosis in which the signs and symptoms appear later in life. [icd10data.com]

  Here the authors report a case of a 9-year-old boy who presented with progressive mental and social deterioration since the age of 2½ years. [annalsofian.org]

  Hirvasniemi A, Lang H, Lehesjoki AE, Leisti J (1994) Northern epilepsy syndrome: An inherited childhood onset epilepsy with associated mental deterioration. J Med Genet 31: 177-182. [omicsonline.org]

• Cerebellar Ataxia

  ataxia, bulbar symptoms, and extrapyramidal and pyramidal signs, but without retinal lesions and rapidly progressive dementia. [icd10data.com]

  Patients may also exhibit cerebellar ataxia, dementia, neuropathy, and myopathy. [blueprintgenetics.com]

  ataxia saccadic intrusion 352641 Autosomal recessive cerebellar ataxia due to GBA2 deficiency 88644 Autosomal recessive cerebellar ataxia type 1 352641 Autosomal recessive cerebellar ataxia with late-onset spasticity 1170 Autosomal recessive cerebelloparenchymal [doczz.net]

Management and treatment There is no curative treatment for NCLs and management is supportive only. [orpha.net]

Treatment protocols and experimental therapies are fully described, with guidance on follow-up and monitoring. [link.springer.com]

You can help by adding to it. ( May 2017 ) Treatment [ edit ] Treatment is limited. Drugs can alleviate the symptoms, such as sleep difficulties and epilepsy. [en.wikipedia.org]

Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. [rarediseases.info.nih.gov]

Prognosis Although all NCLs lead to severe disability, the prognosis is variable with life expectancy ranging from a few hours or days after birth for the congenital form to survival into the fifth decade for patients with the adult-onset form. [orpha.net]

Prognosis There will be mental impairment, worsening seizures and progressive loss of sight and motor skills. Batten's syndrome is often fatal by the late teens or twenties. [patient.info]

Unfortunately, the long-term outlook ( prognosis ) for people with adult neuronal ceroid lipofuscinosis is generally poor. The symptoms tend to become worse over time, resulting in a shortened life expectancy. [rarediseases.info.nih.gov]

[…] with early deaths while juvenile and adult onset forms have a relatively better prognosis. [annalsofian.org]

Etiology To date, at least 10 genetic NCL disorders have been reported and are designated as CLN1 to CLN10. [orpha.net]

To date no specific enzymatic deficiency as the etiology of the condition is known. [healio.com]

[…] of the corpus uteri 141 Spongy degeneration of the brain 324737 SRD5A3-CDG syndrome 54260 Spongy myocardium 83601 SREAT 29822 Spontaneous periodic hypothermia 2806 SSPE 99722 Sporadic achalasia 50944 SSPS 247234 Sporadic adult-onset ataxia of unknown etiology [doczz.net]

Summary Epidemiology The exact prevalence and incidence of this group of disorders are unknown. [orpha.net]

Epidemiology It is a rare condition with a variable incidence across different countries. [patient.info]

Relevant External Links for CLN6 Genetic Association Database (GAD) CLN6 Human Genome Epidemiology (HuGE) Navigator CLN6 Atlas of Genetics and Cytogenetics in Oncology and Haematology: CLN6 No data available for Genatlas for CLN6 Gene Mutations in CLN7 [genecards.org]

Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis. Int J Surg (2007) 5 :225–33. doi:10.1016/j.ijsu.2006.06.015 PubMed Abstract | CrossRef Full Text | Google Scholar 7. [frontiersin.org]

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal storage diseases that involve defective cellular processing of [mayomedicallaboratories.com]

In mice carrying a PPT1 mutation, NtBuHA prevented neuronal cell loss, mitigated behavioral deterioration and increased survival rates. [natureasia.com]

Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY, and the Children’s Miracle Network. The authors have no proprietary interest in any aspect of this article. Reprint requests: Dean P. [journals.lww.com]

Physiotherapy helps affected children retain the ability to remain upright for as long as possible, and prevents some of the pain. Recent attempts to treat INCL with cystagon have been unsuccessful. [en.wikipedia.org]

IMALIVE Provides help with suicide intervention, prevention, awareness, and education and hope through online crisis chat, educational on-campus and virtual college events, and awareness campaigns. [rarediseases.info.nih.gov]

Through defects in endocytosis, autophagy, lysosomal and mitochondrial function, and cytoskeleton, the JNCL gene defect may prevent cells from growing to wild-type size. [publikationen.ub.uni-frankfurt.de]