The patient presented at four years of age with progressive lower extremity weakness and generalized hypotonia. [ncbi.nlm.nih.gov]

Some of the present authors previously reported aWDR45 mutation different from that of the present case in a patient showing clinically Rett syndrome [ 7 ]. [omicsonline.org]

We think that the disease may present with developmental delay in infancy before the appearance of other signs, as in our patient. [annalsofian.org]

• Epilepsy

  The epilepsy phenotypes comprised myoclonic, astatic and absence seizures. Furthermore, the authors suggest that neuroimaging might be normal in childhood. [epilepsygenetics.net]

  Chief Editor Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine Selim R Benbadis, MD is a member of the [emedicine.medscape.com]

  She had a febrile convulsion at 6 months of age but there was no history of epilepsy... May 2016: No to Hattatsu. [readbyqxmd.com]

• Alopecia

  In addition to these general symptoms, which are shared across the NBIAs, there are 10 distinct subtypes which exhibit several additional features including psycho-social difficulties, speech decline, cognitive decline, diabetes, and alopecia. [invitae.com]

• Seizure

  The first phase is marked by global developmental delay and seizures during early childhood. The course is dormant until adulthood, when the patient starts to develop rapidly progressing parkinsonian symptoms. [ajnr.org]

  BPAN is known to be associated with various types of seizures, but there are few reports on infantile spasms, especially in females... [readbyqxmd.com]

  NCV shows distal axonal type sensorimotor neuropathy. [7] Although seizures are described as rare, one study has found the proportion of patient with seizures to be as high as 29%, and 70% of patients showed EEG abnormalities in the form of fast rhythms [annalsofian.org]

  The epilepsy phenotypes comprised myoclonic, astatic and absence seizures. Furthermore, the authors suggest that neuroimaging might be normal in childhood. [epilepsygenetics.net]

  […] accumulation can occur anywhere in the brain, with accumulation typically occurring in globus pallidus, substantia nigra, pars reticula, striatum and cerebellar dentate nuclei. [4] Symptoms can include various movement disorders, neuropsychiatric issues, seizures [en.wikipedia.org]

• Tremor

  […] summary : Mitochondrial Membrane Protein-Associated Neurodegeneration, also known as neurodegeneration with brain iron accumulation 4, is related to neurodegeneration with brain iron accumulation 4, and has symptoms including ataxia, muscle spasticity and tremor [malacards.org]

  These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability). [ghr.nlm.nih.gov]

  His neurological examination revealed mild dysarthria, dystonia, intentional tremor, and spasticity of both lower limbs with exaggerated deep tendon reflexes. Hypomimia and bradykinesia were also noted. Eye fundus examination was normal. [pediatricneurosciences.com]

  Parkinsonism also occurs in about half of individuals reported, with varying combinations of bradykinesia, rigidity, tremor, postural instability, and REM sleep behavior disorder. [ncbi.nlm.nih.gov]

  Parkinsonism is a condition marked by tremor, slowness, rigidity and poor balance. As affected individuals age, they may eventually lose control of voluntary movements. [nbiaalliance.org]

• Hyperreflexia

  Most patients have progressive involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor plantar responses. [genecards.org]

  This is followed by the development of spastic quadriparesis and hyperreflexia and ultimately areflexia and a vegetative state by the end of the first decade. [annalsofian.org]

  Children with PKAN typically manifest gait problems around age 3 and later develop progressive dystonia, dysarthria, rigidity, spasticity, hyperreflexia and extensor toe signs. [nbiaalliance.org]

  Involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor toe signs, was common (13 of 52 patients [25 percent]), as was cognitive decline (15 of 52 patients [29 percent]). [nejm.org]

• Encephalopathy

  “Static encephalopathy” referred to the first phase of the disease, which resembled various neurological disorders in children, including epileptic encephalopathies. The eye of the tiger. [epilepsygenetics.net]

  Without mosaicism, the mutation in male case can cause severe encephalopathy [ 4 ] or may be lethal. Figure 1: A. MRI T2 weighted images show iron deposition at the globus pallidum and substantia nigra (arrows). B. [omicsonline.org]

  We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. [readbyqxmd.com]

  De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nat Genet 2013 ; 45 : 445 –9. [cambridge.org]

• Stroke

  Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemicals, and viruses. Sometimes the cause is not known. [medlineplus.gov]

  National Institute of Neurological Disorders and Stroke. [en.wikipedia.org]

(See Presentation and Workup.) [4, 5, 6] PKAN is relentlessly progressive. The clinical course is characterized by progressive dementia, spasticity, rigidity, dystonia, and choreoathetosis. [emedicine.medscape.com]

Treatment of manifestations: Pharmacologic treatment of spasticity, dystonia, and parkinsonism; psychiatric treatment of significant neuropsychiatric symptoms; physical, occupational, speech, and other therapies as indicated. [ncbi.nlm.nih.gov]

Dopamine agonists Levodopa Deep brain stimulation Symptomatic treatment for dystonia and seizures A 33-year-old woman with a history of global developmental delay and generalized seizures in childhood presented at the age of 21 with parkinsonian symptoms [ajnr.org]

Treatment may require the coordinated efforts of a team of specialists. [nbiaalliance.org]

Treatments may help improve symptoms, relieve pain, and increase mobility. [medlineplus.gov]

Treatments may help improve symptoms, relieve pain, and increase mobility. Multiple system atrophy (Medical Encyclopedia) Progressive multifocal leukoencephalopathy (Medical Encyclopedia) [ Read More ] [icdlist.com]

Diagnosis - Pantothenate Kinase-associated neurodegeneration Prognosis - Pantothenate Kinase-associated neurodegeneration Treatment - Pantothenate Kinase-associated neurodegeneration Resources - Pantothenate Kinase-associated neurodegeneration [checkorphan.org]

(See Presentation and Prognosis.) [7, 8] The disease can be familial or sporadic. [emedicine.medscape.com]

Etiology The exact etiology of PKAN is not known. One proposed hypothesis is that abnormal peroxidation of lipofuscin to neuromelanin and deficient cysteine dioxygenase lead to abnormal iron accumulation in the brain. [emedicine.medscape.com]

Genetics and pathophysiology of neurodegeneration with brain iron accumulation. Curr Neuropharmacol 2013 ; 11 : 59 –79. 6. S. A. Schneider, K. P. Bhatia. [cambridge.org]

"Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)". primary. Current Neuropharmacology. 11 (1): 59–79. doi : 10.2174/157015913804999469. PMC 3580793. PMID 23814539. [en.wikipedia.org]

Neurodegeneration with brain iron accumulation: genetic diversity and pathophysiological mechanisms. Annu Rev Genomics Hum Genet. 2015;16:257–79. CrossRef PubMed Google Scholar 17. [link.springer.com]

Neurodegeneration with Brain Iron Accumulation: Genetic Diversity and Pathophysiological Mechanisms. Annu Rev Genomics Hum Genet. 2015 May 8. Abstract Berti CC, Dallabona, C, Lazzaretti M, Dusi S, Tosi E, Tiranti V, Goffrini P. [tircon.eu]

Symptoms - Pantothenate Kinase-associated neurodegeneration Causes - Pantothenate Kinase-associated neurodegeneration Prevention - Pantothenate Kinase-associated neurodegeneration Not supplied. [checkorphan.org]

Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. Cell Death Differ. 14, 1086 -1094. ↵ Frezza, C., Cipolat, S., Martins de Brito, O., Micaroni, M., Beznoussenko, G. [jcs.biologists.org]

Hamada J, Jeong SY, Fox R, Woltjer RL, Tepper PG, Lahaye LL, Rizzetto E, Harrs CH, de Boer T, van der Zwaag M, Jenko B, Čusak A, Pahor J, Kosec G, Grzeschik NA, Hayflick SJ, Tiranti V, Sibon OCM, Acetyl-4'-phosphopantetheine is stable in serum and prevents [tircon.eu]

Overall, these data promote Drosophila as a useful model for studying PLA2G6-associated neurodegeneration, and for manipulating pathways and therapeutic targets in order to reverse or prevent the deleterious effects of lipid peroxides. [sdbonline.org]

However, vacuolar proteases rapidly degrade proteins taken up by autophagy and thus frequently prevent protein detection in the vacuole. [elifesciences.org]