Expert opinion The key presenting symptoms described above highlight what is already known about the presentation of CLN2 disease. [tandfonline.com]

The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

This review is also intended to serve as a reminder on IEM that could present with ASD as a leading or associated presentation. [frontiersin.org]

Case 1: Seventeen-year-old boy presented with delayed milestones followed by regression, seizures, and intention tremors. On examination child had pyramidal and cerebellar signs. [pediatricneurosciences.com]

High protein concentrations in CSF were also present in most of these patients (data not shown), suggesting the intercurrent association of an inflammatory process and/or impaired blood-brain barrier function with these disorders. [jamanetwork.com]

• Epilepsy

  As metabolic epilepsies are rare [11–13], there may be limited awareness of specific individual epilepsies among clinicians who assess patients in early disease stages. [tandfonline.com]

  However, in both of our cases, epilepsy was controlled with oral folinic acid therapy itself as observed in most of the few published case reports. [pediatricneurosciences.com]

  The term epilepsy is used to describe chronic, recurrent seizures. Ataxia Cerebellar ataxia Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. [rarediseases.oscar.ncsu.edu]

  […] cerebral folate transport deficiency Description Neurodegeneration due to cerebral folate transport deficiency is an autosomal recessive disorder of brain specific folate deficiency, characterized by severe developmental regression, movement disturbances, epilepsy [genome.jp]

  However, no differences were detected in the concentrations of folate in serum and CSF when comparing children with and without epilepsy. [jamanetwork.com]

• Asymptomatic

  Trials of cerliponase alfa are ongoing in younger, potentially asymptomatic patients (<3 years old), and for extended periods to understand the long‑term impact of this ERT [38]. [tandfonline.com]

  Females heterozygous for the SLC6A8 pathogenic mutation are asymptomatic or have mild intellectual delay. [frontiersin.org]

  CEREBRAL FOLATE TRANSPORT DEFICIENCY CAUSED BY MUTATIONS IN FOLR1 Mutational screening of FOLR1 allowed the identification of a homozygous missense mutation, p.Cys105Arg (c.313T>C), in patient 1, which previously has not been described.5,15 The asymptomatic [jamanetwork.com]

• Developmental Disorder

  Introduction Autism spectrum disorder (ASD) is a behavioral developmental disorder defined by the impairment of communication and social interaction. [frontiersin.org]

• Small Head

  Diagnosis A neurological exam will identify symptoms of cerebral folate deficiency such as hypotonia, ataxia, unsteady walking, and small head circumference. MRI of the brain can help determine if there is irregular subcortical white matter. [rarediseases.org]

• Seizure

  Treatment-responsive seizures or delay between early seizures and the development of pharmacoresistance are further challenges, as are ‘watch and wait’ approaches (which may delay diagnosis). [tandfonline.com]

  Medical Term Other Names Description Seizures Epilepsy Seizures are an intermittent abnormality of the central nervous system due to a sudden, excessive, disorderly discharge of cerebral neurons and characterized clinically by some combination of disturbance [rarediseases.oscar.ncsu.edu]

  Cairo et al.[11] reported two children, remarkable motor recovery, and with a significant reduction in seizure frequency. [pediatricneurosciences.com]

  Some early symptoms are intellectual disability, speech difficulties, and development of recurrent seizures in a third of affected children. [rarediseases.org]

  Clinical benefits were limited to 2 patients who experienced only mild transitory improvement in communicative skills and seizure control. [jamanetwork.com]

• Tremor

  Tremor An unintentional, oscillating to-and-fro muscle movement about a joint axis. [rarediseases.oscar.ncsu.edu]

  Case 1: Seventeen-year-old boy presented with delayed milestones followed by regression, seizures, and intention tremors. On examination child had pyramidal and cerebellar signs. [pediatricneurosciences.com]

  Movement problems such as tremors and difficulty coordinating movements (ataxia) can be severe, and some affected individuals need wheelchair assistance. [medlineplus.gov]

  Motor issues such as tremors and lack of muscle control or coordination of voluntary movements (ataxia) can become severe. [rarediseases.org]

  Neurological symptoms include ataxia, tremor, depression, mood disorders, epilepsy and psychosis. The skin eruptions are present at areas exposed to sun and have erythematous and scaly appearance. [frontiersin.org]

• Ataxia

  Ataxia Cerebellar ataxia Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. [rarediseases.oscar.ncsu.edu]

  Neurological examination revealed bilateral spastic quadriparesis with brisk deep tendon reflexes with extensor plantar and ataxia. [pediatricneurosciences.com]

  Motor issues such as tremors and lack of muscle control or coordination of voluntary movements (ataxia) can become severe. [rarediseases.org]

  Movement problems such as tremors and difficulty coordinating movements (ataxia) can be severe, and some affected individuals need wheelchair assistance. [medlineplus.gov]

  Disease is defined by progressive neurological symptoms: ataxia, mental deterioration, subcortical leukoencephalopathy, and ASD (Zafeiriou et al., 2008). [frontiersin.org]

• Cerebellar Ataxia

  Ataxia Cerebellar ataxia Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. [rarediseases.oscar.ncsu.edu]

Diagnostic approach includes wide neuroradiologic, metabolic, and genetic workup (Polšek et al., 2011). [frontiersin.org]

With the advent of treatment for CLN2 disease, it is now imperative to ensure that patients are diagnosed as early as possible to allow treatment to be initiated. [tandfonline.com]

Current treatment includes avoiding copper-rich foods, reducing copper absorption with zinc, chelation therapy to remove copper from tissues, and symptomatic treatment (Mulligan and Bronstein, 2020). [frontiersin.org]

The overall outcome seems to depend on the age at which treatment is initiated, the earlier the treatment, the better outcome. [rarediseases.org]

Journal Am J Hum Genet 85:354-63 (2009) DOI:10.1016/j.ajhg.2009.08.005 Reference PMID:20018644 Authors Cario H, Bode H, Debatin KM, Opladen T, Schwarz K Title Congenital null mutations of the FOLR1 gene: a progressive neurologic disease and its treatment [genome.jp]

Macrocytosis Treatment and Management. Medscape Reference. Available online at http://emedicine.medscape.com/article/203858-treatment. Accessed February 2015. (©2015) Linus Pauling Institute. Vitamin B12. [labtestsonline.it]

Ramaekers et al.[1] noted that folinic acid before age of 6 years has a favorable prognosis and sometimes recover dramatically. This contrasts with children diagnosed at 6 years of age or above who only show partial and delayed recovery. [pediatricneurosciences.com]

In severe neonatal forms, prognosis is unfavorable if severe metabolic crisis develops. In late-onset forms improvement of symptoms has been reported with treatment. [frontiersin.org]

@article{MoleroLuis2015ClinicalEA, title={Clinical, etiological and therapeutic aspects of cerebral folate deficiency}, author={Marta Molero-Luis and Mercedes Serrano and Mar O'Callaghan and Cristina Sierra and Bel{\'e}n P{\'e}rez‐Due{\~n}as and {\`A} [semanticscholar.org]

The determination of the etiology of seizures and epilepsy is vital, as some etiologies have a treatment that may modify the disease course or be managed with a specific approach [10]. [tandfonline.com]

Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol. 2011 May;68(5):615-21. doi: 10.1001/archneurol.2011.80. [medlineplus.gov]

Despite extensive diagnostic investigations, an etiologic diagnosis remained elusive in 24 patients. [jamanetwork.com]

The most common etiology involves one of two autoantibodies blinding to the FRA resulting in a disruption in its function. [rarediseases.org]

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015 Jan;58(1):1–10. 34. Cario H, Smith DEC, Blom H, Blau N, Bode H, Holzmann K, et al. [naturafoundation.es]

A few case series or case reports described reduced 5-MTHF concentrations in CSF that are in the range of mild or moderate 5-MTHF deficiencies observed in our patients and may therefore represent secondary or coincidental forms of CFD without major pathophysiologic [jamanetwork.com]

[…] accounted for epigenetic control of genomic rearrangements of APP gene in fibroblasts of patients with LNS, Nguyen proposed a role of epistasis between mutated HPRT1 and APP genes affecting the regulation of alternative APP pre-mRNA splicing as a possible pathophysiological [frontiersin.org]

Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci. 2013 Jun 4;110(23):9523–8. 80. Bender A, Hagan KE, Kingston N. The association of folate and depression: A meta-analysis. [naturafoundation.es]

Many of them are nowadays diagnosed and successfully prevented by neonatal screening program. [frontiersin.org]

Policy Statement: Folic Acid for the Prevention of Neural Tube Defects. Pediatrics. 1999;104(2):325–327. Reaffirmed May 2012. Pp. 325 -327. Available online at http://pediatrics.aappublications.org/content/104/2/325.full. Accessed March 2015. [labtestsonline.it]

In the rest of the patients, either blood samples were unavailable or hemolysis prevented accurate determination of folate concentrations. [jamanetwork.com]