Neurology · MU Sofia

76. Metabolic disorders of the nervous system: Wilson disease, Niemann-Pick disease type C

Covers Wilson disease, an inherited copper-metabolism disorder, from its ATP7B basis and copper deposition in liver, basal ganglia, cornea and kidneys through hepatic, neurological and psychiatric features, Kayser–Fleischer rings, diagnostic findings and chelation treatment. It then turns to Niemann–Pick disease type C, outlining NPC1 and NPC2 defects, the cholesterol and lipid storage in brain, liver and spleen, the neurological and visceral signs, the vertical gaze palsy, diagnostic clues and miglustat with supportive care.

Inside: 1 section · 2 labelled pictures · 15 flashcards · 2 min

Topic 76 of 88 in the MU Sofia syllabus for Neurology (Medicine, Year 4). The free AceMed note covers it in 1 section, about 263 words (2 min of reading), with 15 flashcards.

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  1. Metabolic disorders of the nervous system - Wilson disease. Niemann-Pick disease type C

Metabolic disorders of the nervous system - Wilson disease. Niemann-Pick disease type C

1. Wilson Disease (Hepatolenticular Degeneration)

Definition: Wilson Disease is an autosomal recessive disorder of copper metabolism caused by mutation of the ATP7B gene, leading to copper accumulation in the:

  • Liver. Basal ganglia (especially putamen). Cornea. Kidneys

Pathogenesis: Defective biliary copper excretion → copper accumulation → tissue damage.

Clinical Features

Hepatic Manifestations: Hepatitis. Cirrhosis. Liver failure

Neurological Manifestations: Tremor ("wing-beating tremor"). Rigidity. Bradykinesia. Dystonia. Dysarthria. Dysphagia. Ataxia

Psychiatric Manifestations: Depression. Personality changes. Psychosis

Eye Findings: Kayser–Fleischer rings (copper deposits in cornea)

Examination

  • Neurological Signs: Parkinsonism. Chorea. Dystonia. Cerebellar signs
  • Ophthalmologic Examination: Slit-lamp examination → Kayser-Fleischer rings

Diagnosis

  • Laboratory Findings: ↓ Serum ceruloplasmin. ↑ Urinary copper excretion (24-hour urine). ↑ Hepatic copper concentration
  • MRI Brain: Basal ganglia abnormalities
  • Genetic Testing: ATP7B mutation

Treatment

  • Copper Chelators: Penicillamine. Trientine
  • Reduce Copper Absorption: Zinc
  • Lifestyle: Low-copper diet

2. Niemann–Pick Disease Type C (NPC)

Definition: Niemann-Pick Disease Type C is a rare autosomal recessive lysosomal storage disease caused by mutations in NPC1 or NPC2 genes, resulting in abnormal intracellular cholesterol and lipid accumulation.

Pathogenesis: Defective lipid transport → accumulation of cholesterol and glycosphingolipids in:

  • Brain. Liver. Spleen

Clinical Features

Neurological Manifestations: Progressive cerebellar ataxia. Dysarthria. Dysphagia. Dystonia. Cognitive decline. Dementia

Characteristic Sign: Vertical supranuclear gaze palsy (difficulty moving eyes vertically)

Psychiatric Symptoms: Psychosis. Behavioral changes

Visceral Manifestations: Hepatosplenomegaly. Neonatal jaundice (some patients)

Examination Findings: Ataxic gait. Eye movement abnormalities. Dystonia. Cognitive impairment

Diagnosis

  • Clinical Suspicion: Ataxia + vertical gaze palsy + hepatosplenomegaly
  • Genetic Testing: NPC1/NPC2 mutations
  • Laboratory Studies: Cholesterol trafficking abnormalities
  • MRI: Cerebellar and cerebral atrophy (late)

Treatment

  • Disease-Specific: Miglustat (slows neurological progression)
  • Supportive: Physiotherapy. Speech therapy. Nutritional support

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