IllnessNeurodegeneration with brain iron accumulation, NBIA; differential diagnosis

Summary

Short information

Neurodegeneration with brain iron accumulation (NBIA) represents a group of rare, genetic neurological disorders characterised by iron deposits in the basal ganglia, detectable by MRI e.g. in the globus pallidus and substantia nigra. NBIA may occur from infancy to adulthood. The disease can progress rapidly or slowly, with long periods of stability. The symptoms can vary widely from case to case. The clinical manifestations relate to muscle function and/or progressive movement disorders, e.g. dystonia, choreoathetosis, spasticity as well as parkinsonism. Progressive dystonia can lead to loss of speech as well as uncontrollable tongue biting, blepharospasm and torticollis. In most forms of NBIA, eye disorders occur in addition such as retinal degeneration and optic atrophy. Cerebral and cerebellar atrophy are also commonly observed. Beta-propeller protein-associated and pantothenate kinase-associated neurodegeneration together account for three quarters of NBIA. In some forms, there are developmental delays, especially regarding the motor skills. Among the cognitive impairments, thinking, perception and other mental processes are often relatively spared. All monogenic inheritance patterns are observed. If NBIA is suspected on the basis of MRI findings, the "core candidate gene panel" includes more than a dozen genes, the broader differential diagnosis about twice as many. Although the molecular genetic yield can reach 85%, a negative DNA test result does not exclude the clinical diagnosis.
Reference: https://www.ncbi.nlm.nih.gov/books/NBK121988/

NP0710

Number of genes

14 Accredited laboratory test

Examined sequence length

19,7 kb (Core-/Core-canditate-Genes)
24,0 kb (Extended panel: incl. additional genes)

Analysis Duration

on request

Material

EDTA-anticoagulated blood (3-5 ml)

Diagnostic indications

NGS +

Gene panel

Selected genes

Name	Exon Length (bp)	OMIM-G	Heredity
ATP13A2	3543	610513	AR
C19orf12	459	614297	AR
COASY	1695	609855	AR
CP	3198	117700	AR
DCAF17	1563	612515	AR
FA2H	1119	611026	AR
FTL	528	134790	AD
PANK2	1713	606157	AR
PLA2G6	2421	603604	AR
RAB39B	642	300774	XLR
SCP2	1644	184755	AR
WDR45	1086	300526	AR
CRAT	1881	600184	AR
REPS1	2467	614825	AD, AR

Informations about the disease

Clinical Comment

Neurodegenerative disorders characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation in the brain + the presence of axonal spheroids, usually limited to the CNS

Synonyms

Alias: Neurodegeneration with brain iron accumulation, NBIA
Allelic: Acne inversa, familial, 3 (PSEN1)
Allelic: Hyperostosis cranalis interna (SLC39A14)
Allelic: Myopathy, distal, with rimmed vacuoles (SQSTM1)
Alzheimer disease, type 3 (PSEN1)
Alzheimer disease, type 3, with spastic paraparesis + apraxia (PSEN1)
Alzheimer disease, type 3, with spastic paraparesis + unusual plaques (PSEN1)
Cardiomyopathy, dilated, 1U (PSEN1)
Cerebellar ataxia (CP)
Choreoacanthocytosis (VPS13A)
Dementia, frontotemporal (PSEN1)
Dystonia 28, childhood-onset (KMT2B)
Frontotemporal dementia +/or amyotrophic lateral sclerosis 3 (SQSTM1)
Fucosidosis (FUCA1)
Glutaricaciduria, type I (GCDH)
HARP [Hyperprebetalipoproteinemia, Acanthocyt., Retinit. pigment., Pallidal degen.] syndrome (PANK2)
Hemosiderosis, systemic, due to aceruloplasminemia (CP)
Hyperferritinemia-cataract syndrome (FTL)
Hypermanganesemia + dystonia 2 (SLC39A14)
Hypoceruloplasminemia, hereditary (CP)
Infantile neuroaxonal dystrophy 1 (PLA2G6)
Kufor-Rakeb syndrome (ATP13A2)
L-ferritin deficiency, AD + AR (FTL)
Leukoencephalopathy with dystonia + motor neuropathy (SCP2)
Mental retardation, XL 72 (RAB39B)
NESCAV [NEurodeg., Spasticity +/- Cerebellar Atrophy or cortical Visual impairment] syndrome (KIF1A)
Neurodegeneration with ataxia, dystonia + gaze palsy, childhood-onset (SQSTM1)
Neurodegeneration with brain iron accumulation 1 (PANK2)
Neurodegeneration with brain iron accumulation 2A, 2B (PLA2G6)
Neurodegeneration with brain iron accumulation 3 (FTL)
Neurodegeneration with brain iron accumulation 4 (C19orf12)
Neurodegeneration with brain iron accumulation 5 (WDR45)
Neurodegeneration with brain iron accumulation 6 (COASY)
Neurodegeneration with brain iron accumulation 7 (REPS1)
Neurodegeneration with brain iron accumulation 8 (CRAT)
Neurodegeneration, childhood-onset, with brain atrophy (UBTF)
Neuropathy, hereditary sensory, type IIC (KIF1A)
Paget disease of bone 3 (SQSTM1)
Parkinson disease 14, AR (PLA2G6)
Pick disease (PSEN1)
Pontocerebellar hypoplasia, type 12 (COASY)
Spastic paraplegia 30, AD (KIF1A)
Spastic paraplegia 30, AR (KIF1A)
Spastic paraplegia 35, AR (FA2H)
Spastic paraplegia 43, AR (C19orf12)
Spastic paraplegia 78, AR (ATP13A2)
Waisman syndrome (RAB39B)
Woodhouse-Sakati syndrome (DCAF17)

Heredity, heredity patterns etc.

OMIM-Ps

Multiple OMIM-Ps

ICD10 Code

G31.8-

Bioinformatics and clinical interpretation

No text defined