Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of disorders varied in genetic etiologies, clinical presentations, and radiological features. [ncbi.nlm.nih.gov]

• Feeding Difficulties

  Mental deterioration, emaciation, severe feeding difficulties, and visual impairment occur commonly in the late stages of the disease. The disease has its onset in the first or second decade of life. [medicinenet.com]

• Diplopia

  Average age of onset is 66 years and other common features include vertical gaze palsy, diplopia, and photophobia, which are not features of PKAN. [ncbi.nlm.nih.gov]

• Vertical Gaze Palsy

  Steele-Richardson-Olzewski syndrome (also known as progressive supranuclear palsy) (OMIM 260540 ). Average age of onset is 66 years and other common features include vertical gaze palsy, diplopia, and photophobia, which are not features of PKAN. [ncbi.nlm.nih.gov]

• Facial Grimacing

  grimacing painful muscle spasms HSD is a genetic disease. [healthline.com]

• Onset at Age <20

  Differential diagnoses include the following: Early-onset Parkinson disease including parkin type of juvenile Parkinson disease and PLA2G6 -associated dystonia-parkinsonism may initially present similarly to atypical PKAN, with onset between age 20 and [ncbi.nlm.nih.gov]

• Dysarthria

  The Hallervorden-Spatz syndrome (HSS) is a rare condition characterized by extrapyramidal and pyramidal signs, dystonia, dysarthria, retinal degeneration, dementia and a progressive course. [ncbi.nlm.nih.gov]

• Ataxia

  We studied a 27-year-old woman who died after a 6-year history of progressive dementia, dystonia, ataxia, apraxia, spasticity, choreoathetosis, visual and auditory hallucinations, and optic atrophy. [ncbi.nlm.nih.gov]

  Clinical findings Movement disorder (blepharospasm, grimacing, facial and neck dystonia, tremors, chorea) and cerebellar ataxia (gait ataxia, dysarthria), progressive extrapyramidal signs, and dementia Lab Absent serum ceruloplasmin due to a mutation [medical-dictionary.thefreedictionary.com]

• Hyperreflexia

  Neurologically, opisthotonus, rigidity of extremities, dystonia, hyperreflexia, profound emaciation, and bilaterally positive Babinski signs were present. [ncbi.nlm.nih.gov]

  Described features include 9,11 : progressive dementia extrapyramidal signs (rigidity, dystonia, choreoathetosis) corticospinal signs (spasticity, hyperreflexia) dysarthria retinitis pigmentosa tremors The clinical course is usually relentlessly progressive [radiopaedia.org]

  Pyramidal signs including spasticity and hyperreflexia. Retinitis pigmentosa Atypical PKAN : Usually presents around 12-14 years of age. Slower progression. Speech and behavioural problems predominate in the early stages. [genetics4medics.com]

  Clinical manifestations include progressive muscle spasticity; hyperreflexia; muscle rigidity; dystonia; dysarthria; and intellectual deterioration which progresses to severe dementia over several years. [icd10data.com]

• Pyramidal Tract Signs

  Table-1: Diagnostic features of Hallervorden spatz disease [11] Obligate Features Collaborate Features Exclusion Features Onset during first two decades Pyramidal tract signs Non progressive nature of the disease Progressive nature of the disease Progressive [medresearch.in]

  tract signs. 1 Choreoathetotic movements or tremor may also be present but these features have not been described in isolation. [jnnp.bmj.com]

  Spasticity, hyperreflexia, and other signs of corticospinal tract involvement are common and eventually limit ambulation. [ncbi.nlm.nih.gov]

• Cranial Nerve Involvement

  nerve involvement (rare) These disorders include the following: Hypobetalipoproteinemia type 1 (FHBL1; OMIM 615558 ) Hypobetalipoproteinemia type 2 (FHBL2; OMIM 605019 ) FHBL1, FHBL2, and ABL share the findings of acanthocytosis, dysarthria, neuropathy [ncbi.nlm.nih.gov]

(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.com]

• Dyslipidemia

  Pantethine has been already proved to be an effective treatment for hyperlipoproteinemia and dyslipidemia in human patients, and a dose of up to 1,200 mg pantethine per day for 24 weeks is tolerated without any side effects ( 20, 21 ). [doi.org]

• Visceromegaly

  Affected children have coarse facial features and visceromegaly consistent with a lysosomal storage disease. [ncbi.nlm.nih.gov]

Prognosis: Fatal; Mean duration disease after symptom onset = 11 yrs Treatment: No curative treatment. Iron chelation ineffective. Palliative treatment with Baclofen, trihexyphenidyl, stereotactic pallidotomy, Pantothenate (vit B5). [neuroradiologycases.com]

Western blot analysis with specific hPANK2 antibodies was used to investigate the effect of the RNAi treatment (48 h after RNAi treatment) on hPANK2 protein levels. GAPDH was used as a loading control. [doi.org]

Standard Therapies Treatment There is no specific treatment for individuals with PKAN. Treatment is directed towards the specific symptoms that appear in each individual. [rarediseases.org]

[…] disorders across the lifespan (pediatric, adult, and geriatric populations) Includes interventions and methods of treatment for the outcomes patients may experience [books.google.com]

A 12 year old patient with the Hallervorden-Spatz syndrome and suffering from acute intestinal obstruction during treatment with benztropine is presented. [ncbi.nlm.nih.gov]

[…] choreoathetosis, torsion spasm–dystonia, parkinsonism, cerebellar ataxia, speech impairment, mental deterioration, generalized rigidity Imaging Cerebral atrophy by CT DiffDx Dementia with extrapyramidal motor defects, Wilson's disease Management None Prognosis [medical-dictionary.thefreedictionary.com]

Prognosis: Fatal; Mean duration disease after symptom onset = 11 yrs Treatment: No curative treatment. Iron chelation ineffective. Palliative treatment with Baclofen, trihexyphenidyl, stereotactic pallidotomy, Pantothenate (vit B5). [neuroradiologycases.com]

The neurological outcome has an adverse effect on the prognosis, which may result in fatality. Therefore, early diagnosis and intervention may prevent a devastating neurological damage. [journals.lww.com]

Treatment and prognosis Treatment is with iron chelation therapy, using agents such as desferrioxamine 10. [radiopaedia.org]

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

These findings suggest that obtaining a buffy coat and bone marrow biopsy may aid in the diagnosis of Hallervorden-Spatz syndrome and ultimately provide information regarding etiology. [ncbi.nlm.nih.gov]

Relevant External Links for PANK2 Genetic Association Database (GAD) PANK2 Human Genome Epidemiology (HuGE) Navigator PANK2 Atlas of Genetics and Cytogenetics in Oncology and Haematology: PANK2 No data available for Genatlas for PANK2 Gene A novel pantothenate [genecards.org]

Pantothenate kinase-associated neurodegeneration EPIDEMIOLOGY PKAN was first described by Drs. Julius Hallervorden and Hugo Spatz in 1922. [flipper.diff.org]

The clarification of the role of oxidative distress in the pathophysiology of the syndrome will fill a large void in the understanding of the condition. [ncbi.nlm.nih.gov]

His main research interest is in movement disorders, specifically the merging of clinical, electrophysiological and imaging methods to provide insights into the pathophysiology of conditions like dystonia and Parkinson's disease. [books.google.com]

MRI scans can also confirm a diagnosis; abnormal low intensities can indicate iron accumulation in the brain. [4] Prevention [ edit ] Children of affected individuals are obligate carriers for aceruloplasminemia. [en.wikipedia.org]

Management Chelation with desferrioxamine, fresh-frozen plasma (FFP) to reduce iron in the liver may improve neurologic signs/symptoms; antioxidants (vitamin E), zinc and deferasirox (iron chelator) may prevent hepatic and pancreatic damage. [medical-dictionary.thefreedictionary.com]

There is no known way to prevent it. Hallervorden-Spatz disease; Pantothenate kinase-associated neurodegeneration; PKAN; NBIA Gregory A, Hayflick S. Neurodegeneration with brain iron accumulation disorders overview. [nlm.nih.gov]

Also, antioxidants such as vitamin E may be used along with a chelator or oral administration of zinc to prevent tissue damage, particularly to the liver and pancreas. [nbiadisorders.org]

There’s no known way to prevent HSD. Genetic counseling is recommended for families with a history of the disease. [healthline.com]