Presentation
We present video case reports of 4 individuals with neuroferritinopathy chosen to illustrate how this disorder can present and subsequently progress clinically. [ncbi.nlm.nih.gov]
Clinical description The disease presents typically in the fourth to sixth decades, although cases with symptoms in their late teens have been observed. [orpha.net]
The relevant articles were reviewed with a focus on the pathophysiology, clinical presentation, differential diagnoses, and management of NF. [academiccommons.columbia.edu]
Methods : case work up Results : Family 1: A 31 year old female presented with complaints of abnormal movements for last 5 years, starting in her right leg and progressing rapidly to other limbs. [mdsabstracts.org]
Respiratoric
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Hoarseness
He had hoarseness of voice with difficulty in swallowing and a recent change in his behaviour. With normal birth history and developmental milestones, there is no consanguineous marriage in the family. [mdsabstracts.org]
[…] used to make speech This can make a person’s speech difficult to understand in several different ways, including stuttering, slurring, or soft or raspy speech Dysphonia (movement of the vocal cords is forced and strained) Results in a jerky, quivery, hoarse [nbiacure.org]
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Aspiration
Death can occur secondary to dystonia, impaired swallowing, and aspiration pneumonia. TREATMENT There is currently no cure for NBIA. Treatment is symptomatic and supportive. Iron chelating medications have been attempted without significant effect. [secure.ssa.gov]
Psychiatrical
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Behavior Disorder
disorders Behavioral disturbances Behavioral problems Behavioral/psychiatric abnormalities Behavioural/Psychiatric abnormality Psychiatric disorders Psychiatric disturbances [ more ] 0000708 Constipation 0002019 Dementia Dementia, progressive Progressive [rarediseases.info.nih.gov]
Face, Head & Neck
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Hypomimia
While 35% developed facial hypomimia and bradykinesia not directly related to their dystonia; only one individual developed a pure rest tremor, and another had tremor present at rest and on intention. [academic.oup.com]
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Dull Facial Expression
facial expression 0000338 Laryngeal dystonia 0012049 Micrographia 0031908 Mutism Inability to speak Muteness [ more ] 0002300 Neurodegeneration Ongoing loss of nerve cells 0002180 Progressive Worsens with time 0003676 Rigidity Muscle rigidity 0002063 [rarediseases.info.nih.gov]
Neurologic
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Cognitive Impairment
The clinical features of the disease are highly variable, and include a movement disorder, behavioral abnormalities, and cognitive impairment. [ncbi.nlm.nih.gov]
Neurologic signs include parkinsonism, abnormal postures and movements (dystonia), ataxia, muscle rigidity, spasticity, and cognitive impairment. MRI of the brain can be helpful to demonstrate the accumulation of iron in the basal ganglia. [secure.ssa.gov]
They're all characterized by variable presentation of chorea, dystonia, and parkinsonism, cognitive impairment, and psychiatric disturbance. 0:31 The CAG repeat diseases comprise Huntington's disease, DRPLA, SBMA, and SCA1, 2, 3, 6, 7 and 17. [hstalks.com]
The original family carried a clinical diagnosis of Huntington's disease, but the lack of cognitive impairment over many years of follow-up first alerted us to this new disease. [academic.oup.com]
Some individuals with aceruloplasminemia develop cognitive impairment, which can progress to dementia. Behavioral or emotional changes (e.g., depression) may also occur. [rarediseases.org]
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Hyperreflexia
[…] ferritin Low ferritin level Reduced serum ferritin [ more ] 0012343 Disinhibition 0000734 Dysarthria Difficulty articulating speech 0001260 Dyskinesia Disorder of involuntary muscle movements 0100660 Emotional lability Emotional instability 0000712 Hyperreflexia [rarediseases.info.nih.gov]
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]
Spasticity and hyperreflexia as well as retinopathy are often present. The atypical form most commonly presents in the second decade of life and its clinical features are less homogeneous, with less severe extrapyramidal and pyramidal signs. [doi.org]
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Cerebellar Sign
With the exception of the reported cerebellar signs, the clinical presentation of the patients with the 498InsTC and 646InsC mutations fall within the spectrum we have seen in patients with 460InsA. [academic.oup.com]
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Babinski Sign
sign 0003487 Blepharospasm Eyelid spasm Eyelid twitching Involuntary closure of eyelid Spontaneous closure of eyelid [ more ] 0000643 Cavitation of the basal ganglia 0007007 Choreoathetosis 0001266 Decreased serum ferritin Low ferritin level Reduced [rarediseases.info.nih.gov]
signs ( Vidal et al ., 2004 ). [academic.oup.com]
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Cerebellar Sign
With the exception of the reported cerebellar signs, the clinical presentation of the patients with the 498InsTC and 646InsC mutations fall within the spectrum we have seen in patients with 460InsA. [academic.oup.com]
Workup
(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]
Serum
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Dyslipidemia
Kompoliti’s include the gender differences in Parkinson’s disease and other movement disorders, studies to define the effect of neuroleptics on weight, risk for diabetes and dyslipidemia in patients with Tourette syndrome, and define the current status [books.google.com]
Treatment
Management and treatment Treatment is of the manifestations of the disease and includes levodopa, tetrabenazine, benzhexol, sulpiride, diazepam, clonezepam and deanol for the movement disorder and botulinum toxin for painful focal dystonia. [orpha.net]
The disorder provides a direct link between disordered iron storage and a neurodegenerative disease, opening new avenues for treatment by altering brain iron stores in addition to symptomatic treatments such as local Botulinum toxin and oral anti oxidants [ncbi.nlm.nih.gov]
[…] and prognosis No disease-specific treatment is available and symptomatic management is recommended 2. [radiopaedia.org]
Prognosis
Prognosis The movement disorder is progressive, involving additional limbs in five to ten years and becoming more generalized within 20 years. The documents contained in this web site are presented for information purposes only. [orpha.net]
[…] caudate, substantia nigra, and cerebellar nuclei, these are reflective of cystic changes 3 T1 : hypointense ring surrounding aforementioned cystic changes 3 GRE/SWI : markedly hypointense ring surrounding aforementioned cystic changes 3 Treatment and prognosis [radiopaedia.org]
Management and prognosis Monitoring Asymptomatic patients with proven homozygosity for C282Y Yearly exam of skin, heart, liver, joins, and (in men) testes iron %sat Patients with hereditary hemochromatosis hepatic cirrhosis Q6mo serum AFP and liver ultrasound [faculty.washington.edu]
(See Presentation and Prognosis.) [7, 8] The disease can be familial or sporadic. [emedicine.medscape.com]
Etiology
This chapter summarizes the genetic etiology, pathological, radiological, and clinical data from all published data to date and suggested potential new avenues for therapy. [ncbi.nlm.nih.gov]
Non-genetic etiologies are discussed, including medications, structural lesions, psychogenic causes, and metabolic abnormalities. This book describes in detail the latest clinical and etiological information regarding the causes of chorea. [books.google.com]
Etiology Neuroferritinopathy is caused by mutations in the ferritin light chain ( FTL ) gene (19q13.3-q13.4) and is inherited in an autosomal dominant manner with high penetrance. [orpha.net]
Epidemiology
Summary Epidemiology Prevalence of neuroferritinopathy is unknown. To date fewer than 50 cases have been reported. [orpha.net]
Epidemiology Map of England Neuroferritinopathy was first discovered in 2001, with its first case being reported in Cumbria from Northern England. [dict.eudic.net]
Symptoms affecting movement (dystonia) have also been treated with L-Dopa, orphenadrine, benzhexol, sulpiride, diazepam, clonazepam, and deanol. [ 4 ] Parkinsonian symptoms were not decreased by L-Dopa. [ 1 ] Iron supplements should be avoided. [ 4 ] Epidemiology [research.omicsgroup.org]
The 460InsA insertion was not present in the 100 anonymized samples from the Cumbrian population collected as part of a resource for genetic epidemiology. [academic.oup.com]
They show variable incidence, and, from an epidemiological point of view, it is also important to note that these diseases are extremely rare and some are generally confined to specific populations ( Dusek and Schneider, 2012, 2013 ). TABLE 1. [doi.org]
Pathophysiology
Management strategies, pathophysiology, and associated medical and psychiatric problems associated with chorea are also addressed. [books.google.com]
The relevant articles were reviewed with a focus on the pathophysiology, clinical presentation, differential diagnoses, and management of NF. [academiccommons.columbia.edu]
This raises the possibility that mitochondrial dysfunction may play an important part in the pathophysiology of neuroferritinopathy. [jmg.bmj.com]
Prevention
Prevention of secondary complications: Adequate caloric intake; physiotherapy to maintain mobility and prevent contractures. Agents/circumstances to avoid: Iron supplements are not recommended. NOTE: The above information is for processing purpose. [medigoo.com]
Long-term surveillance for neuroferritinopathy can include: Regular assessment of nutrition and caloric intake Physiotherapy to maintain mobility and prevent contractures (permanent tightening of a muscle or joint). [nbiacure.org]
Ferritin stores essential iron inside cells and prevents the iron causing damage. The error leads to large amounts of iron and ferritin collecting in the cells and causing problems with body movements. [news.bbc.co.uk]
Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo : a novel therapy for Parkinson's disease. Neuron 27, 899–909 (2003). [doi.org]