Tag Archives: Ophthalmology

Wilson’s disease

= hepatolenticular degeneration. Autosomal recessive condition with copper accumulation due to impairment of biliary excretion. Leads to cirrhosis, via a stage indistinguishable from chronic active hepatitis, plus neurological disease. Caused by mutations of the ATP7B gene that codes for a copper transporting ATPase – over 300 mutations known, varying geographically.

Clinical Presentation

Usually presents in late teens but has been described as young as 3yrs. Neurological presentation tends to be older (by 5 years) although they usually have subclinical liver disease. Hepatic disease varies from elevated aminotransferases, through chronic liver disease to fulminant hepatic failure (often with Coombs negative haemolytic anaemia), about 5% of presentations.

Basal ganglia involvement leads to movement disorders viz:

  • Tremor
  • Chorea
  • Parkinsonism
  • Gait disturbances
  • Dysarthria

Other neurological signs are:

  • Psychiatric symptoms
  • Depression
  • Neuroses
  • Personality changes
  • Psychosis

It can also cause:

  • Epilepsy
  • Sunflower cataracts
  • Aminoaciduria
  • Renal stones
  • Osteomalacia with spontaneous fractures


Can be tricky given multisystem disorder and limited sensitivity/specificity of tests. Heterozygotes may also have borderline results. If typical presentation then diagnosis can be made on basis of:

  • Kayser-Fleischer rings
  • Low serum ceruloplasmin levels (<0.2g/L)
  • Genetic screening of limited utility due to number of known mutations

May require extensive tests of copper metabolism especially with severe hepatic presentation, where up to 50% can have normal ceruloplasmin (an acute phase reactant) eg

  • Non-caeruloplasmin-bound serum copper
  • 24-h urinary copper excretion – can be abnormal in other chronic liver diseases, however. Excretion of >25micromol/24hr after penicillamine is a diagnostic test in children.
  • Liver copper content (>250mcg/g dry weight) – best test when others ambiguous.

In fulminant hepatic failure the following features may suggest diagnosis:

  • Haemolysis (Coombs negative)
  • Alkaline phosphatase surprisingly low viz ALP:Bilirubin ratio of less than 1 has 86% sensitivity and 50% specificity in children


  • Diet – chocolate, liver, nuts, mushrooms, and shellfish are high in copper
  • Zinc – reduces copper absorption from gut. Monotherapy is an option for maintenance therapy.
  • Chelation
    • D-penicillamine – but note side effects, and some patients with neurological disease deteriorate on starting treatment
    • Trientine – perhaps less side effects
  • Liver transplantation – curative, except for long-standing neurological disease. Indicated for fulminant hepatic failure.


  • Neurological function
  • Liver function tests
  • 24hr urinary copper excretion (aim for less than 2 micromol/d)
  • Non-ceruloplasmin bound copper of 50-150mcg/L

Marfans syndrome

Chromosome 15, fibrillin locus but lots of different mutations.  Not linked to collagen genes, despite clinical overlap with Ehlers-Danlos etc.

Neonatal cases can occur, always severe, with cardiac abnormalities and contractures.

Clinical diagnosis – Beighton (he of benign hypermobility score fame) published Berlin criteria, later came Ghent criteria

  • family history important, else
  • involvement of the skeleton, plus
  • at least 2 other systems, with a minimum of 1 major manifestation (ectopia lentis, aortic dilatation/dissection, or dural ectasia). 

Skeletal – Tall, disproportionate arm span (>1.05x height – 8cm wider than tall at 160cm) and digits, anterior chest deformity, hypermobility (joint laxity), scoliosis/lordosis, high arched palate and crowded teeth.

Eyes – Myopia, corneal flatness, subluxation of lens (ectopia lentis).

Cardiac – MVP, MR, AR and aortic root dilatation (chart of normal measurements available).  Cardiac examination is often normal despite abnormal echo findings! Aortic aneurysm and dissection can be life threatening.

Pulmonary blebs affect some people, recurrent pneumothorax.  Dural ectasia (widening of lumbosacral spinal canal) on CT is very common, hence why a major manifestation, although symptoms unusual.

Life expectancy is reduced, particularly in males. [Omim]