Neurodegeneration with Brain Iron Accumulation 2B

Alternative Names

  • NBIA2B
  • Neurodegeneration with Brain Iron Accumulation, PLA2G6-Related
  • Neuroaxonal Dystrophy, Atypical
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WHO-ICD-10 version:2010
OMIM Number

610217

Mode of Inheritance

Autosomal recessive

Gene Map Locus

22q13.1

Description

Neurodegeneration with Brain Iron Accumulation 2 (NBIA2B) is one of the PLA2G6-associated neurodegeneration (PLAN), which refers to the overlapping phenotypes that result from PLA2G6 mutations.  NBIA2B is characterized by cerebellar and cerebral atrophy, increased iron deposition in the basal ganglia and an 'Eye of the tiger' sign on MRI scans.  Histological investigations reveal axonal swellings or spheroids, Lewy bodies in the substantia nigra and throughout the brain as well as neurofibrillary tangles.  Patients exhibit symptoms such as ataxia, dysmetria, chorea of limbs, dystonia, dysarthria, bradykinesia, hypertonia, dysphagia, spasticity, seizures, speech delay and cognitive decline.  The condition also causes optic atrophy and nystagmus.  Affected individuals may suffer from behavioral issues such as hyperactivity, emotional lability, impulsivity, poor attention span, and diminished social interaction.  Atypical neuroaxonal dystrophy has a later onset compared to Infantile neuroaxonal dystrophy (INAD), usually affecting children between the ages of 4 to 6.  However, in some cases, the condition only manifests in the teenage years.  The disorder is also more slowly progressive than INAD and has a variable phenotype. It does not appear to have a racial or gender bias. 

Diagnosis is made based on clinical features and brain imaging studies as well as by genetic analysis.  Treatment is symptomatic and supportive.  Patients benefit from pharmacological therapy such as anti-seizure medication and baclofen for dystonia, ambulatory aids, physical therapy and speech therapy. 

Molecular Genetics

The disorder follows an autosomal recessive pattern of inheritance.  It is caused by homozygous or compound heterozygous mutations in the PLA2G6 gene which encodes a phospholipase A2 enzyme.  While PLA2G6 variants associated with NBIA2A are mainly truncating mutations that impair enzyme activity, those associated with NBIA2B are generally missense mutations that have a comparatively milder effect on enzyme function.

Epidemiology in the Arab World

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Other Reports

United Arab Emirates

Al-Shamsi et al. 2016 reported on an Emirati patient (610217.1) with NBIA2B exhibitting developmental regression, hypertonia, failure to thrive, scoliosis, skin abnormalities, and typical MRI findings. A variant in PLA2G6 was identified UC003aux.1:c.154G>A (p.V52M). This variant only exists in this isoform and does not conform to HGVS nomenclature. The patient harbors another homozygous variant, as well as compound heterozygous variants, in ACOX1 and SACS respectively.  

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