Niemann-Pick disease type C
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Niemann-Pick disease type c (NPD-C or just NPC) is an autosomal recessive lysosomal storage disorder classed under Niemann-Pick disease on account of clinical similarities, namely hepatosplenomegaly and variable involvement of the central nervous system.
NPD-C is inherited as an autosomal recessive disorder with an estimated minimal incidence of 1/120,000 live births 2.
NPD-C has a variable age of presentation, ranging for the neonatal period into adulthood.
hepatobiliary signs and symptoms 2
neonatal presentation: cholestatic liver failure
infancy and childhood presentation: hepatosplenomegaly
neurological signs and symptoms 2
neonatal and infant presentation: delayed development milestones
childhood presentation: ataxia, falls, supranuclear vertical gaze palsy, cognitive impairment (e.g. poor school performance)
adolescent and adult presentation: ataxia, supranuclear vertical gaze palsy, psychiatric illnesses, cognitive impairment
Radiographic features are limited, and MRI is the modality of choice.
Reported abnormalities on MRI brain include:
cerebral (particularly frontal lobe) and cerebellar atrophy 2,3.
white matter high T2 signal, particularly parieto-occipital periventricular regions 3
deep grey matter and hippocampal atrophy (reported in the adult-onset patient) 4
Treatment and prognosis
Management typically focuses on symptom control, such as antiseizure medications for epilepsy control. There is ongoing research regarding potential disease-modifying therapies, such as of N-acetyl-L-leucine which has some evidence to improve neurological function 6.
Although invariable NPD-C leads to premature death, in almost all cases before the age of 50 years of age, the rate of progression is highly variable. Age of onset of systemic features (e.g. hepatosplenomegaly) is not a good predictor, whereas the age at which neurological impairment becomes evident does correlate with survival: the earlier the onset of neurological signs and symptoms, the shorter the life expectancy 2.