28 Wilson's Disease

Morning Report
Chief Residents
July 28, 2011

16 year old F with emesis

• 1 wk of RUQ pain, NV, fatigue
• NB, daily. +Green on day of
presentation
• RUQ pain
– worsened by movement
– relieved by rest
– crampy in nature
– begins epigastric, radiates to L side
• Seen in ER 4 d PTA for emesis
– dx w/ viral gastro
– slight elevation seen in LFTs
• Similar episode ~6 mo ago w/ nl
lab work
History
• PMH: None
• Menstrual Hx: NL, regular
cycles with manageable
cramps
• PSH: None
• Meds: None
• Imm: UTD
• Social Hx:
– LAHW M, D, Sib
– Working on a cattle farm for the
summer.
– Will be a senior in HS
– No drugs, sex, smoking, EtOH.
– Active varsity soccer player
• FH: No Hx of GI or AI disease
• Allergies: None

• GI
– Hepatitis
Differential Diagnosis
– Drug induced hepatitis
– Autoimmune hepatitis
– Peptic ulcer disease
– SBO
– Appendicitis
– Viral gastroenteritis
– Cholecystitis
– Pancreatitis
• Repiratory
– PNA
• Onc:
– Abdominal, intracranial or hepatic
mass
• Endo
– DKA
• Neuro
• ID
– Increased ICP
– Post-concussive syn
– Intracranial bleed
– Migraine HA
– STI
– EBV
• Other
– Drug exposure, overdose, withdrawl
– Pregnancy
– Cyclic vomiting syndrome

Physical Exam
Vitals: T36.6 HR67 RR14 BP 116/58
O2sat: 100% BMI 22
General: Well appearing F, tired but arousable
Heent: Scleral Icterus, Jaundice noted under tongue, MM, PERRLA,
EOMI, TMs WNL
CV: RR, no murmur, NL S1 and S2
Resp: CTAB, no crackles, wheezes, rales
Abd: Soft. Bowel sounds are normal. No distension, no ascites and no
mass. + Hepatosplenomegaly (Liver edge is palpable at about 5
FBBCM, span is about14 cm) or splenomegaly. No tenderness. No
hernia.
Neuro: AOx3, GCS 15, unable to conduct serial 7s, strength,
senasation, tone WNL, CN II-XI WNL
Skin: + Diffuse jaundice visualized, particularly on stomach. No palmar
erythema, no spider veins noted

138 / 3.6 | 110 / 22 | 16 / 1.2 < 99
Ca 8.1
4.8 | 2.9
11.9 | 6.7c
92 /\ 53
20
9.8 > 5.8 / 18.4

Wilson’s Disease
• AR defect in Copper transport resulting in
liver deposition and damage
• 1 in 30,000 live births

Dietary Copper
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2 diseases involving Cu transport
Wilson’s Disease
• Decreased transport
of Cu from liver to
bile
• Cu excess
• …More to come....
Menkes’ Disease
• X linked
• Severe
neurodegeneration
• Defect in Cu transport
• Cu deficiency
• Seizures, FTT, DD,
Kinky silver hair

Pathophysiology
• Mutation in gene ATP7A on Chromosome 13
• Decreased incorporation of copper into
apoceruloplasm
– Decreased formation and secretion of ceruloplasm
• Decreased copper excretion in bile
– Loss of primary excretory mechanism
• Both increased liver concentrations of Cu
– Cu forms free radicals and injures hepatocytes

Fatty infiltration and portal
fibrosis
Pathology
Cirrhosis

• Teenage years
Signs and Symptoms
• Silent disease until intra-hepatic and extra-hepatic copper
deposition begins to manifest clinically
– Age 6-30
• Incidental elevated LFT Overt liver failure
• 282 patients:
– Neurologic 69%
• Parkinsonism, Dystonia, Cerebellar and Pyramidal sings
– Hepatic 15%
– Hepato-neurologic 2.5%
– Osseomuscular 2%
– Pure psychiatric 2%
– Asymptomatic 5%

Our patient’s slit lamp exam

Fulminant Hepatic Failure
• Usually teens or young adults
• Symptoms
– Variceal bleeding
– Portal hypertension
– Decreased synthetic function
– Associated with hemolytic anemia
• Due to release of copper into circulation
• Hemoglobinuria, dark urine, renal failure
• Ominous prognosis
• Indication for urgent liver transplant

Diagnosis
• Coomb’s negative hemolytic anemia
• Elevated bilirubin & LFTs with low AlkPhos
• Low serum ceruloplasm and high urinary
copper excretion
• Gold Standard: High Tissue Content of
Copper on Liver Biopsy (> 250ug/g dry
weight)

Uptodate.com

• 2 phases
– Removal of copper
Treatment
– Preventing re-accumulation
• Evaluation of siblings

• D-penicillamine
– Cu chelating moiety
Chelators
– Reduces the affinity of proteins for copper, allowing
previously protein bound copper to bind penicillamine
– Excretion via urination
– 30% of pts do not tolerate long term 2/2 SE
– Early SE- drug sensitivity reactions
– Late SE: nephrotic syndrome, bone marrow toxicity,
hepatotoxicity, Goodpasture

• Trientine
– Cu chelator
Chelators
• Forms a stable complex with four nitrogens and Cu
• Increases renal excretion
– Lower incidence of SE
– Higher price

Zinc
• Interefers with absoption of Cu
• Induces metallothionein in enterocytes
which has a high Cu affinity binding of
lumical copper and prevention of entry into
circulation fecal excretion during
exterocyte turnover

Dietary Recommendations
• Limit intake of foods high in copper
– Water testing if gathered from well
– Evaluation if homes have copper water pipes

Fulminant Hepatic Failure
• Emergent Liver Transplant
• Supportive Care

Liver Transplant Complications
• Infection
– Peri-operative
–Post-op
– Immunosuppresion
• Acute Rejection
• Hepatic Artery
Thrombosis
• Biliary leak
• Chronic Rejection
• PTLD
• Disease Recurrence
• Morbidity associated
with immunosuppresive
drugs

https://louisville.edu/medschool/gimedicine/division-lecture-files/marsano-lectures/Post-Liver-Transplant%20Complications.pdf

Back to our patient….
Listed as 1A for Liver Transplant
Transferred to ICU
Started on Penicillamine
Developed ARF
Transitioned to Trientine
Improved LFTs and mental status
Discharged home after 11d admission

Objectives
• Review the differential diagnosis of emesis
• Review the biologic role of copper
• Compare Wilson’s disease to Menke’s
disease
• Review the symptoms, diagnosis and
treatment of Wilson’s disease
• Briefly review complications associated
with liver transplant