Differential Diagnosis of Rapid Progressive Dementia

Table 3: List of Mutations Causing Syndromes with Associated Pre-senile Dementia Disease

Gene Alzheimer’s disease Frontolobar degeneration

APP (amyloid precursor protein) PS1 (presenilin) PS2 (presenilin) ND

Huntington’s disease Dentato-rubro-pallido-

luysian atrophy Neuroacanthocytosis

Familial encephalopathy with

neuroserpin inclusion bodies Neuroferritinopathy Hallervorden Spatz SCA

Wilson’s disease

Cerebrotendinous xanthomatosis Ornithine transcarbamylase deficiency Prion

CADASIL Fabry’s disease Cerebral amyloid angiopathies

British Danish Dutch

Icelandic Meningovascular

Adult GM2 gangliosidosis Krabbe’s disease

Niemann-Pick type C

Metachromatic dystrophy Gaucher type 3

Kuf’s disease ceroid Mucolipidosis I

Adult Pelizaeus–Merzbacher disease Adrenoleukodystrophy Lafora body disease

Adult polyglucosan body disease Mitochondriopathy

PLOSL polycystic lipomembraneous Osteodysplasia with sclerosing

leukencephalopathy (Nasu-Hakola disease) Sanfilippo B

Vanishing white-matter disease mcuopolysaccharidosis Genetic CJD

FFI GSS

Notch3

Alpha-galactosidase A BRI BRI

APP Cystatin C Transthyretin Hexoaminidase A

Galactocerebrosidase NPC1

Arylsulfatase A

Glucocerebrosidase ND

Sialidase

Proteolipid ALD protein Laforin various

mitochondrial DAP12 TREM2

NAGLU (N-acetylglucosaminidase) EIF2B1-5

19 X

13 (point mutation) 13 (duplication) 21 20 18

15/5 14 18 22 1

ND 6 X X 6

Various

Mitochrondial 19

MAPT (microtubule-associated protein tau) CHMP2B (chromatin-modifying protein 2B) VCP (valosin-containing protein) GRN (granulin) Huntington Atrophin 1

Chorein Neuroserpin

Ferritin light polypeptide PANK2 Various

Human copper-transporting ATPase ATP7B Mitochondrial sterol-27 hydroxylase Ornithine transcarbamylase PRNP

Chromosome 21 14 1 9

17 3 9

17 4

12

9, X 3

19 20

Various 13 2 X

20

17

12 (type 1) 14 (type 2) 1 (type 3) 2 (type 4) 3 (type 5)

APP = acute-phase protein; ATP = adenosine triphosphate; CADASIL = cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CJD = Creutzfeldt-Jakob disease; FFI = fatal familial insomnia; GSS = Gerstmann-Sträussler-Scheinker; ND = not determined; PLOSL = polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; PRPN = prion protein; SCA = spinocerebellar ataxia.

huntingtin gene on chromosome 4. The prevalence in Europe is up to 8/100,000. The cognitive decline starts typically in middle age with neuropsychiatric symptoms, followed by subcortical dementia and extrapyramidal signs such as choreatiform hyperkinesias. In addition to familial disorders, a higher frequency of metabolic disorders is ascertained in the differential diagnosis of pre-senile dementia.

EUROPEAN NEUROLOGICAL REVIEW

Mitochondrial disorders (incidence 2/10,000), Wilson’s disease (incidence 1/30,000–300,000) and lysosomal storage diseases such as Fabry’s disease or Niemann-Pick type C (incidence 1/8,000) are examples of this entity, some of which have known causative mutations. Usually, metabolic disorders cause a subcortical dementia characterised by disturbance of vigilance and attention; memory

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