Hepatolenticular Degeneration. Friedrich’s ataxia.
Hepatolenticular degeneration - Wilsons Disease
This disease is caused by mutation to the gene coding for ATP7B which is located on chromosome 13.
Clinical manifestations
- Kay-Fleischer rings around the periphery of the cornea sue to deposition of copper in Descemets membrane
- Dysarthria
- Gait abnormalities/ataxia
- Dystonia - abnormal limb movements
- Tremor
- Parkinsonism - paucity of expression and movement
- Drooling
- Others - Risus sardonicus, Chorea, Cognitive impairment, Seizures, Hyperreflexia, Myoclonia, Urinary incontinence.
Diagnosis
- Urinary copper >100micrograms
- Serum cerulopasmin <20mg /dl
- Kayser–Fleischer rings
- Molecular genetic testing - over 200 mutations are known
- MRI – abnormal
- Penicillamine challenge - 500mg dose is given at the beginning of the 24 hour urine collection and then again at 12 hours. Urinary copper excretion greater than 1600 micrograms per 24 hours is indicative of Wilsons disease
Treatment:
- Copper chelating agents - oral admin of penicillamine 1g/day in two doses before meal for adults. 0.5-0.75g/day for patients younger than 10yrs.
- Zinc - impairs the GI absorption of copper. Zinc acetate 25-50mg three times/day for adults
Untreated patients will die of the complications from other systems including hepatic, renal and haematological as well as neurological problems. Liver transplantation should be considered for patients with progressive neurologic disease.
Friedreich’s Ataxia
- One of the most prevalent spinocerebellar ataxias
- Autosomal recessive, mutation on chromosome 9 which produces Frataxin
Pathomorphology
- Degeneration of posterior columns especially fasciculus gracilis and is most intense in cervical region
- Loss of larger cells in basal ganglia of dorsal root
- Degeneration of pyramidal pathways, spinocerebellar pathways
- Atrophy of brainstem and of superior cerebellar peduncle
- Gliosis of cerebellar white matter
- Loss of thickly myelinated sensory fibres and degeneration of dorsal roots of peripheral nerves
- Cardiomyopathy
- Cortico-ponto cerebellar pathways and nuclei olivae inferior are intact which is a clear distinction from cerebrocerebellar ataxia
Clinical feature
- Onset most often between 8 and 15 years, before age of 20
- Progressive spinocerebellar ataxia; affects gait, intention tremor
- Impaired position sense, two point discrimination and stereognosis
- Positive Rombergs sign
- Distal loss of the joint-muscular and vibration sensation in the legs
- Knee and Achilles areflexia
- Positive Babinski
- Secondary symptoms: dysarthria, pyramidal symptoms in legs, absence of reflex in arms
- Tertiary symptoms: nystagmus, optic atrophy, semsoneuronal deafness
- Scoliosis and kyphoscoliosis
- Pes cavus and pes equinovarus or so called Freidrich’s foot
Examination
- EMG show signs of degeneration
- CT and MRI show atrophy of spinal cord. Medulla oblongata size reduced
- CSF normal