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A CASE OF WilSOn’S

disease
UNIT III
ASSOCIATE PROFESSOR:
DR.V.USHA PADMINI M.D.,

ASSISTANT PROFESSORS:
DR.P.RAJAMAHENDRAN M.D.,
D R . G . A N U R E K H A M . D .,
CASE HISTORY

 Vaishnavi, 13 years old girl admitted on 11/7/18 with chief


complaints of
 Difficulty in taking oral feeds since past 1 month

 History of Presenting Illness:


 Patient was apparently normal 1 year ago
 Initially patient had difficulty in speaking followed by
 Difficulty in walking
 Involuntary movements involving all four limbs and
 Difficulty in swallowing food more since the past 1 month
Case History

 No H/O headache
 No H/O head injury
 No H/O drug intake
 No H/O fever
 No H/O dogbite / vaccinations
 No H/O yellowish discolouration of urine
 No H/O abdominal pain
 No H/O altered sensorium
 No H/O altered bowel habits
 No H/O seizures
 No H/O loss of consciousness
Clinical Photographs
Past History

 First born child to third degree consanguinous marriage parents


 Born by normal vaginal delivery
 Cried immediately after birth
 Milestones were delayed
 Academic performance poor

 Not K/C/O DM/HTN/BA/Epilepsy


Family history

3rd degree
consanguinous
marriage
Autosomal Recessive Inheritance
General Examination

 Patient conscious
CVS : S1S2 heard
 Responds to oral commands
 Thin built
 Ill nourished RS: NVBS +
No added sounds
 Slurring of speech
 Pallor +
Abdomen: Soft
 Not Icteric No organomegaly
 No cyanosis /No clubbing
 No significant generalised lymphadenopathy
 No neurocutaneous markers
CNS examination
 Higher Mental Functions:  VITALS:
 Patient awake
 Alert  BP: 90/60 mm/Hg
 Responds to commands  Pulse: 94 /min
occasionally  RR:16/min
 Slurring of Speech  SpO2: 99%
 Right handed
 Inappropriate laughter

 Appearance and behaviour-


vacuous smile
Cranial nerves

 Normal
MOTOR SYSTEM RIGHT LEFT

BULK: Inspection No wasting No wasting

Palpation: UL- Arm circumference 16 cms 16 cms

Forearm circumference 14 cms 14 cms

Lower limbs: Thigh 26 cms 26 cms

Leg 20 cms 20 cms

TONE: Upper limb Rigidity+ Rigidity+

Lower Limb Rigidity+ Rigidity+

SUPERFICIAL REFLEXES:

Corneal reflex Present Present

Conjunctival Reflex Present Present

Pharyngeal Reflex Present Present

Abdominal Reflex Present Present

Plantar Reflex Flexor Flexor

- -
POWER RIGHT LEFT
Upper limb:
Shoulder : Abduction 5/5 5/5
Adduction 5/5 5/5
Elbow : Flexion 5/5 5/5
Extension 5/5 5/5
Wrist : Flexion 5/5 5/5
Extension 5/5 5/5
Lower limbs:
Thigh : Flexion 5/5 5/5
Extension 5/5 5/5
External /Internal Rotation 5/5 5/5
Knee : Flexion 5/5 5/5
Extension 5/5 5/5
Foot : Dorsiflexion 5/5 5/5
Plantar flexion 5/5 5/5
DEEP REFLEXES RIGHT LEFT
Jaw jerk Normal
Biceps Jerk C5, C6 ++ ++
Triceps Jerk C6,C7,C8 ++ ++
Supinator jerk C5, C6 ++ ++
Knee jerk L3,L4 ++ ++
Ankle Jerk S1,S2 + +
Cerebellar Signs:
UL: Finger Nose Test Not cooperative Not cooperative
Finger Nose Finger Test Not cooperative Not cooperative
Dysdiadochokinesia absent absent
LL : Knee Heel Test Not cooperative Not cooperative

Involuntary Gittery movements Present


Rhomberg’s sign Not cooperative Not cooperative

Spine and Cranium Normal Normal


Glabellar tap POSITIVE
SENSORY SYSTEM RIGHT LEFT
SUPERFICIAL
Touch Normal Normal
Pain Normal Normal
Temperature Normal Normal
DEEP SENSATION:
Pressure Normal Normal
Deep Pain Normal Normal
Vibration Normal Normal
Joint Vibration Normal Normal
CORTICAL SENSATION:
Tactile localisation Normal Normal
Two Point Discrimination Normal Normal
Stereognosis Normal Normal
Graphaesthesia Normal Normal
Blood Investigations

CBC Urea 33 Sodium 130

Hb 12.1 gm% Sugar 101 Potassium 4.0

Creatinine 0.9 Calcium 8.3


TC 4300
T.bilirubin 0.9 PT test 11.2
DC 55/42/3
SGOT 154 PT control 12.7
RBC 4.1
SGPT 97 APTT test 23.6
PCV 33%
ALP 132 APTT 22.0
control
PLATELETS 1 lakh S. Protein 6.2 INR 0.9
Blood Investigations

Urine albumin Nil Hb -11.5 T.Bil : 1.4


Urine sugar Nil Tc -6200 SGOT: 154
Deposits 3-4 pus cells Dc-56/40/4
RBC -3.7 SGPT : 97

PCV -31% ALP :132


Peripheral Smear:
Plts -1.5 Protein :5.6
Normal Study lakhs

Serum
ceruloplasmin 24 hrs urine copper
6 mcg/day
<3 mg/dl
Slit lamp
examination
reveals
Kayser
Fleischer
Rings
Neurologist Opinion

 Patient was apparently normal till 1 year ago


 For the past 1 yr, had progressive development of abnormal movements
involving all four limbs
 H/O difficulty in speaking and swallowing since 1 yr more since 2
weeks
 O/E Conscious, not communicating, open mouth,
 Blink rate reduced , open mouth
 Rigidity of all 4 limbs
 Dystonia involving both upper and lower limbs
 Bradykinesia, Toe walking +
 Impression : ?Young onset parkinson disease with dystonia and
 ? Neuro wilson
USG ABDOMEN & pelvis

 Liver 9.2 cm in size.


 Increased echoes
 Mild Splenomegaly
 Portal vein 9 mm
 Pancreas normal
 Both kidneys normal
 No free fluid abdomen

IMPRESSION: Mild Splenomegaly


Altered Liver Echoes
d
--Bilateral
symmetrical T2
FLAIR
hyperintensity
involving basal
ganglia, thalamus
-- may represent

-WILSON’S
DISEASE

MRI BRAIN
DIAGNOSIS

THIS IS A CASE OF NEURO WILSON’S

• Age • KF ring
• Tremors
• 2nd decade • Serum ceruloplasmin
• Involuntary mvts low
• Rigidity
Treatment

Tab Zinc Acetate 50 mg BD

Tab Trihexyphenidyl 2 mg 1/2 -1/2 -1/2

Tab Levodopa 1-1-1

Tab BCT 1-0-1

Physiotherapy
Sibling Screening

 Kevin ,7 yrs old younger brother of the pt with no


neuropsychiatic symptoms with good academic performance.

CBC RFT , LFT Ophthal


opinion
• Hb-11.2gm/dl • Urea- 34
• TC- 7000 • Sugar-116 • NO
• Dc-62/36/2 • Creatinine- evidence
• RBC -4.2 0.8 of
• PCV-34% • T.Bil -0.9 • KF RING
• Plts- 1.8 lakhs • SGOT- 79
• SGPT -52
• Protein -6.4
DIFFERENTIAL DIAGNOSIS

Early onset
Parkinson’s
disease
Neurodegeneration
with Brain Iron
Accumulation

Neuro
Acanthocytosis
WilSOn’S disease
Wilson’s disease
WilSOn’S diSEASE

 First described by Kinnier Wilson


 Genetic disorder of copper metabolism which mainly affects liver
but also involves brain, eyes, kidneys.
 Excess copper accumulation is due to inherited defect in
hepatobiliary excretion of copper.

 Autosomal Recessive inheritance.


 Worldwide distribution with prevalence of 1:30000
 Frequency of carriers 1:90
 Missense or non sense mutation in ATB 7B gene
Copper Metabolism

s
pathogenesis

Decreased ATP 7B

• Decrease in biliary copper excretion

Impaired copper incorporation to ceruloplasmin

• Increase in free copper in circulation

Toxic effects of excess copper to tissues

• Free radical injury,Alterations in cellular


antioxidants, Lipid peroxidation of membranes
Pathophysiology

s
Pathology

 Early stage is characterised by mild hepatic enlargement which


further progresses to fibrosis and cirrhosis.
 Microscopically, characterised by diffuse cytoplasmic copper
accumulation followed by periportal inflammation with
mononuclear cell infiltrates.

 Distinctive mitochondrial changes


Widening of mitochondrial membranes
Increase in density and granularity of
matrix and replacement by large vacuoles.
Clinical features

 Presymptomatic
 Asymptomatic with only hepatic abnormalities
 Hepatic disease
 Chronic active hepatitis
 Cirrhosis with hepatic insufficiency
 Active hepatitis with /without hemolytic anemia
Clinical features

 Skeletal and articular abnormalities:


 Spine and Knee Involvement most common
 Osteoporosis
 Osteomalacia
 Spontaneous Fractures
 Adult Rickets
 Osteoarthritis
 Osteochondritis Dissecans
 Chondrocalcinosis
 Subchondral Cyst Formation
Clinical features

 Neurologic signs and  Renal Disease:


symptoms  Glycosuria
 Dystonia with rigidity and  Aminoaciduria
contractures  Bicarbonaturia
 Tremors  Hypercalciuria
 Dysphonia and Dysarthria  Nephrocalcinosis
 Gait disturbance  Hyperphosphaturia
 Choreiform movements  Uricosuria

 Psychiatric symptoms
 Hematologic abnormalities:
 Neuroses to Psychoses
 Hemolytic anemia
Ophthalmic
manifestations

Kayser
Fleischer Ring
Sunflower
Cataract

Reversible
with
treatment
Diagnosis

 Diagnosis of Wilson’s is suspected in persons 3- 40 yrs of age


with unexplained hepatic or neuropsychiatric manifestations.

Liver copper: <50 mcg/gm


Serum free copper : 8-12 mcg/dl
24 hrs urinary copper : >100 mcg/24 hrs

Serum ceruloplasmin :20 -50 mg/dl


Molecular genetic studies for gene
mutations
Diagnosis

Serum Ceruloplasmin
(<20mg/dl)

Serum free copper


Liver copper concentration
(>250mcg/gm ) (>25mcg/dl)

24 hrs urinary copper


excretion (>100 KF Ring
mcg/day)
Diagnosis in acute hepatitis

s
Non immunopathic
hemolytic anemia

Unconjugated
hyperbilirubinemia ALP/ Bilirubin < 4

Elevated serum and AST /ALT >2.2


urinary copper levels
Diagnostic of wilson’s
disease in acute liver
failure
Leipzig Score
f
Treatment

 Aim of treatment is to abolish symptoms and prevent progression


of the disease.

Chelating Agents
BAL
Penicillamine Maintenance therapy
Trientene Zinc
f
Chelating agents

Chelating agents
remove copper from
potentially toxic
sites within cells
and detoxify and
excretes it.
Chelating agents

 Indicated for symptomatic patients with hepatic ,neurologic/


psychiatric disease.

Penicillamine Trientene

Dose: 750-1000 mg tds Dose: 750-1000 mg tds

Lupus like reaction


Sideroblastic anemia
Marrow suppression

Both drugs require dose reduction in pregnancy and surgery.


Long term D-penicillamine therapy

Progeric changes of skin Elastosis Perforans


serpiginosa

 Worsening of neurological symptoms seen in 10% of patients .


f
Zinc Salts

-Acts by blocking
intestinal absorption
of dietary copper.
-Stimulates the
biosynthesis of
endogenous chelators
in liver like
metallothioneins.
Zinc in the treatment
Zinc Therapy

Dose : 150 mg thrice/day

Indicated in asymptomatic patients


Maintenance therapy for previously
symptomatic patients

Can be used in penicillamine intolerance


Gastric intolerance – side effect
liver transplantation

 INDICATIONS:
 Wilsonian acute liver failure
 Severe hepatic insufficiency unresponsive to therapy.

 Copper toxicity can also be removed by Plasmapheresis,


Exchange transfusion and albumin dialysis.

 Neurological symptoms improve after transplantation.

 No specific therapy for wilson’s is needed after the perioperative


period of liver transplantation.
Monitoring therapeutic efficacy

 Non ceruloplasmin bound copper :


 Single best parameter to gauge the adequacy of treatment.
 In untreated , inadequately treated , non compliant patient, serum
non ceruloplasmin bound copper > 25 mcg/dl.
Therapeutic efficacy

x
Chelating therapy Zinc

During early phase , Urinary copper levels >125


urine copper levels >1000 mcg/24 hrs – inadequate
mcg/24 hrs treatment or non compliance

Non ceruloplasmin copper <


On prolonged treatment, 10mcg/dl
levels remain at 250 -500 Urine Zinc >1000mcg/dl
mcg/ 24 hrs
Urine copper <250 mcg/dl
Prognostic Score

1 2 3 4

Serum bilirubin 100-150 151-200 201 -300 >300


(mcmol/L)
AST (U/L) 100 -150 150 -300 301 -400 >400

INR 1.3 -1.6 1.7 -1.9 2.0 -2.4 >2.4

WBC (10/L) 6.8 -8.3 8.4 -10.3 10.4 -15.3 >15.3

Albumin 34 -44 25 -33 21 -24 <21


(gm/L)

 Score >11 associated with higher probability of death without


liver transplantation.
References

 Schiff ‘s hepatology
 Harrison’s textbook of Internal Medicine, 19th edition
 EASL clinical Practical Guidelines: Wilson’s disease,
Journal of Hepatology.
 Wilson’s disease emedicine, Medscape.
Thank you
C