GENE /08 (O)

Clinical study of children with Wilsons disease

AUTHORSDr R. K. Gupta MD, FIAP . Associate Professor, Pediatric Medicine Dr Alok Goyal MD. Senior Resident, Pediatric medicine Institute: SPMCHI, S.M.S Medical College, JAIPUR. INDIA

INTRODUCTION
Autosomal recessive inherited disorder of Copper

Excretion Accumulation of Copper in the Liver, Brain, Kidneys and Cornea. The gene for WD is located on the long arm of chromosome 13( 13q14.3). Gene encodes ATP7B, a copper-transporting P-type ATPase expressed primarily in liver. More than 500 mutations identified. Incidence 1/50,000 to 1/100,000 births.(1/30,000 in SEA).

CLINICAL PRESENTATIONS
From early childhood to adulthood Hepatic Acute hepatitis, chronic hepatitis, fulminant liver failure,

cirrhosis, PHT

Neuropsychiatric Tremors, dysarthria, dystonia, chorea, incoordination, behavioural abnormalities, depression, mood changes. Others Hemolytic anemia ( coombs negative) Fanconis syndrome Rare: Renal failure, Arthritis, Infertility, Hypoparathyroidism

DIAGNOSIS

Urinary copper - >100 ugm/day Urinary copper (Post Penicillamine) - >500 mcg/day Serum ceruloplasmin - <20mg/dl Serum copper (non-ceruloplasmin bound) <10 mcg/dl Liver biopsy- steatosis, cirrhosis Liver copper ->250mcg/gm dry wt Mutational analysis MRI brain

TREATMENT
Avoidance of copper containing food materials Demineralization of drinking water Drugs

Penicillamine Zinc Trientine ( triethylene tetramine dihydro chloride) Ammonium tetrathiomolybdate

Liver transplantation

AIM & OBJECTIVES

To study the clinical presentation of children with Wilson disease To study biochemical features of Wilson disease To evaluate diagnostic value of different tests in children with Wilson Disease

A
In

hospital based retrospective study

children diagnosed as Wilson disease among admissions during year 2008-2010. SPMCHI, S.M.S Medical college, Jaipur, a tertiary care pediatric hospital.

At

Average age at presentation- 7 year (3.5 year -9 year). Male to female ratio was 3:7. Two cases (20%) had a positive family history of Wilson disease. 90% had hepatic presentation, 30% had neurological manifestations.

Jaundice, hepatomegaly and ascites were common manifestations (>50%) Hepatic encephalopathy-2 One child also had anemia, thrombocytopenia with renal calculi. Two children had neurological manifestations in addition to hepatic features.

Kayser-Fleischer rings were seen in five cases only. Serum ceruloplasmin levels low (<20 mg/dl) -7 cases
normal range (20-40 mg/dl) -3 cases

24 hours urinary copper levels after Penicillamine were > 100-500, >500-1000 and >1000 mcg/24 hrs in 1, 4, 5 cases respectively. Serum copper was not done in any case.

100%

F E M A L E

Y E S

N O

N O

N O R M AL

>1000

NO

Y E S Y E S L O W

500-1000

50%

MA L E

100-500

0%

Liver function tests were deranged in all cases with hepatic involvement (9 cases). Liver biopsy (done in 2 cases )-showed cirrhosis MRI brain (3 cases with neurological presentation )- basal ganglia involvement seen in all. Mutation analysis was not done in any case.

CONCLUSION
WD more common in females. Age at presentation >3.5 years. In children hepatic manifestations are predominant. KF rings are absent in about 50% children. Significant family history in some cases. S. ceruloplasmin and 24 hrs U. Copper ( Post Penicillamine ) are most sensitive tests.

CONCLUSION
Wilson disease should be suspected in every case of unexplained liver disease (acute, chronic, and fulminant) as if diagnosed early, it is treatable. No single test is diagnostic, so clinical assessment and a battery of tests is needed for diagnosis.

THANKS