Symptoma

Mitochondrial Membrane Protein-Associated Neurodegeneration

MPAN

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

Table 1 presents the patients’ demographic and clinical data. The mean age of onset was 8.5 years (range 3–15 years) and the time between first symptoms and the present study was 13 years (range 8–23 years). [link.springer.com]

Together with these findings, the results of the present studysuggest that TCS might support the discrimination betweendifferent genetic subtypes of NBIA. [docslide.net]

  • Turkish

    Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient. [pediatricneurosciences.com]

    Hanagasi and Vincenzo Bonifati, The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN, Parkinsonism & Related Disorders, 39, (64), (2017). Angela Deutschländer, Takuya Konno and Owen A. [doi.org]

  • Asymptomatic

    Heterozygotes (carriers) are asymptomatic. Offspring of a proband. [ncbi.nlm.nih.gov]

    Sonografic detection of basal Anglia lesions In asymptomatic and symptomatic Wilson disease. Neurology. 2005;64:1726–32. CrossRef PubMed Google Scholar 5. Walter U, Wagner S, Horowski S, Benecke R, Zettl UK. [link.springer.com]

  • Drooling

    […] feeding tube to help minimize weight loss (which becomes more frequent with disease progression) and to reduce the risk of aspiration pneumonia Glycopyrrolate or transdermal scopolamine patch to reduce the volume of secretions in those with excessive drooling [ncbi.nlm.nih.gov]

  • Hypomimia

    Hypomimia and bradykinesia were also noted. Eye fundus examination was normal. Magnetic resonance imaging of brain revealed symmetric, hypointensity of bilateral globus pallidus, and substantia nigra in the T2-weighted images [Figure 1]. [pediatricneurosciences.com]

  • Urinary Incontinence

    Affiliated tissues include brain, globus pallidus and eye, and related phenotypes are urinary incontinence and abnormality of saccadic eye movements Genetics Home Reference : 25 Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder [malacards.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]

  • Postural Instability

    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]

    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]

  • Polyneuropathy

    Scherer, Stephan Züchner, Rudolf Martini and Jan Senderek, Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies, The American Journal of Human Genetics, 99, 3, (607), (2016). [doi.org]

    Sonographic substantia nigra hypoechogenicity in polyneuropathy and restless legs syndrome. Mov Disord. 2009;24:133–7. CrossRef PubMed Google Scholar 4. Walter U, Krolikowski K, Tarnacka B, Benecke R, Czlonkowska A, Dressler D. [link.springer.com]

  • Babinski Sign

    sign Dysarthria Iron accumulation observed on brain MRI in both the globus pallidus and substantia nigra ( Figure 1B ). [ncbi.nlm.nih.gov]

  • Motor Symptoms

    Joseph Jankovic, Ask the Experts: Differentiating Parkinson’s disease from other parkinsonian disorders, Parkinson’s Disease: Diagnosis, Motor Symptoms and Non-Motor Features, 10.2217/ebo.13.228, (136-140), (2013). [doi.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]

  • Excessive Drooling

    drooling or difficulty controlling secretions Tracheostomy as indicated for difficulty managing secretions Over-the-counter fiber supplements and/or stool softeners to treat constipation, which is likely caused by a combination of immobility, diet, and [ncbi.nlm.nih.gov]

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]

The risk of having an affected child in further pregnancies is of 25%.Management and treatmentThere is currently no curative treatment. Management strategies focus on the medical and surgical palliation of symptoms. [malacards.org]

Neuropsychiatric symptoms may require treatment by a psychiatrist. Medical providers also may seek to manage the disease by performing regular eye exams, as well as neurological tests for dystonia, spasticity and parkinsonism. [nbiadisorders.org]

Symptomatic treatment for spasticity with baclofen and physiotherapy were initiated in our patients. NBIA refers to an inherited heterogeneous group of disorders. [pediatricneurosciences.com]

Marco Nuñez and Pedro Chana-Cuevas, New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases, Pharmaceuticals, 10.3390/ph11040109, 11, 4, (109), (2018). Vykuntaraju K. Gowda, Arundhati Patil, Varunvenkat M. [doi.org]

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]

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]

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 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]