INTRODUCTION
Wilson’s disease (WD) or hepatolenticular degeneration first described by Kinnier Wilson in 1912,is an autosomal recessive hereditary disease,with an incidence of about 1 in 30,000 in most parts of the world.The disease is not manifested clinically before 4 to 5 years of age because it takes time for copper to accumulate to toxic levels in the liver till such age.The average age for hepatic symptoms is 10~14 years,compared with 19~22 years for neurologic symptoms.Various hepatic forms like acute hepatitis,chronic hepatitis,and cirrhosis of liver,acute fulminant hepatic failure can occur in early childhood［1］.During the hepatic stage,Kayser-Fleischer (KF) ring may be absent.Neurological manifestations appear in the second decade and early symptoms are incoordination,tremor,dysarthria and mask like facies.We report here WD presented with neurological manifestations without hepatic involvement.
CASE REPORT
A 10-year-old boy,born from non-consanguineous parents admitted at KHS hospital,department of Pediatrics,presented with pain in abdomen off and on,distension of abdomen and involuntary movement of the limbs since 3 months ago.He was apparently well 3 months back when he started developing progressively increasing abdominal swelling mainly in left upper abdomen associated with off and on mild pain.This was associated with progressive pallor without any major bleeds.There was history of episodic abnormal posture and rigidity of limbs.No history of jaundice,hematemesis,melena,hemoptysis,blood transfusions in the past,fever,rash,joint pains,chest pain,history of drug intake,bleeding disorders in the family.Immunized as per national schedule,hepatitis B vaccine was not given.The other children had no history of similar illness.His developmental milestones were normal.
On examination his vital signs were stable.There was no pallor,icterus,clubbing or significant lymphadenopathy.Per Abdominal examination revealed distension with everted umbilicus.Non tender to palpation,spleen was palpable 6 cm below left costal margin,hard in consistency with smooth and regular surface,liver was not palpable.Percussion showed no free fluid in abdomen.Respiratory examination was unremarkable.Cardiovascular examination was unremarkable.Neurological examination showed dystonia,choreiform movements of the limbs,exaggerated deep tendon reflexes and ankle clonus was present.Babinski sign was positive.Muscle power was grade 4 in upper and lower limbs.
Complete blood count revealed hemoglobin concentration of 7 gm%.The white blood cell count was 3,500 cells/cu.mm (Neutrophil 56%,Lymphocytes 42%,Eosinophils 2%) and Platelets count was 90,000/mm3.Reticulocyte count was 0.6%.Liver function test were normal.His prothrombin and activated partial thromboplastin time were within normal limits.Bone marrow revealed normocellular marrow with erythroid hyperplasia.Serum Ceruloplasmin level was 14 mg/dl,serum copper was 65 mcg/dl.24 hours urinary copper was 1,032 mcg/24 h.Serum calcium and phosphate levels were 7 mg/dl and 3.5 mg/dl respectively.Hemoglobinuria and glucosuria were absent on urine examination.Ultrasonography of abdomen was normal.The serum electrolytes and arterial blood gas analysis were normal.Non-contrast CT Scan brain revealed bilateral symmetrical hypodensity in basal ganglia and putamen.On MRI,T2-weighted images revealed high signal hyperintensities in the bilateral basal ganglia and putamen region,same region is hypointense on T1-weighted images.Ophthalmoscopic examination by slit lamp showed Kayser-Fleischer rings in both eyes (Figure 1).
Figure 1 Bilateral K-F ring was present
After one week of penicillamine therapy the child developed pancytopenia with hemoglobin level 6gm%,TLC:3,200/cu mm and platelet count was 40,000/cu mm,for which the drug was with drawn for one week till hematological stability was regained.Therapy was again started,and the child responded very well to therapy.His dystonia and abnormal movements were reduced.
DISCUSSION
WD is an autosomal recessive condition characterized by inability of the liver to transport and store normally absorbed dietary copper resulting in abnormal deposition of copper in the basal ganglia,eyes,liver and other tissues［1,2］.The gene for WD (ATP7B) was mapped to chromosome 13.The average intake of copper in India ranges from 5.7~7.1 mg/d and is higher than the reported 0.34~1.1 mg/d in Western countries［3,4］.The clinical presentations of WD are liver and neuropsychiatric problems.Chronic active hepatitis,culminating in cirrhosis is the most common hepatic presentation,but some patients present with fulminant liver failure.Central nervous system pathology results from copper deposition in the basal ganglia and presented with signs and symptoms,such as drooling,speech changes,incoordination,tremor,difficulty with fine motor tasks,and gait difficulties.Psychiatric manifestations include compulsive behavior,aggression,depression,impulsive behavior,and phobias［4］.Neurological onset in WD has been record in children as young as 6 years and in adults as old as 52 years.In addition,hemolytic anemia,hypersplenism and renal tubular acidosis have also been reported［1,2］.KF ring may be absent in young patient with liver disease but are always present in patient with neurological symptoms.KF ring,is characterised by brown rings around the cornea in the eye that result from copper deposition in Descemet’s membrane of the cornea.The rings fade and disappear with appropriate chelation therapy in 3~5 years in the reverse order of appearance.
Diagnosis is based on clinical evaluation along with biochemical and neuroimaging confirmation.Biochemical studies reveal a low serum ceruloplasmin level (< 20 mg/ dl) and increased urinary copper excretion (>100 μg copper per 24 hours).Hepatic copper estimation,of more than 250 μg/g of dry tissue ( Normal 15~55 μg/g) is the most definitive method of diagnosis［5］.In WD patients,neuroimaging abnormalities occur in gray matter of lentiform,caudate and thalamic nuclei［6,7］.CT scans of the brain revealed hypodense regions in the basal ganglia (caudate nucleus,putamen,and globus pallidus).Ventricular dilatation,brainstem atrophy,and posterior fossa atrophy are other possible findings.Liver biopsy must then be done at the earliest opportunity,as hepatic copper may remain elevated despite years of therapy and clinical improvement.The disease is treated with lifelong use of chelating agents such as D-penicillamine or trientine hydrochloride,drugs that help remove copper from tissue.Patients will also need to take vitamin B6 and follow a low-copper diet,which means avoiding mushrooms,nuts,chocolate,dried fruit,liver,and shellfish.Scholastic and vocational rehabilitation is required for neurological handicaps.Liver transplantation is effective in patients with fulminant WD that does not respond to the usual treatment.Use of zinc for maintenance therapy and for treatment of asymptomatic sibs［8］.A poor prognosis has been reported in patients who discontinue chelation therapy.In our case neurological manifestation was the presenting feature without any association of hepatic involvement detected clinically and by liver function studies.The case was diagnosed from low serum ceruloplasmin level,KF rings and significant neurological recovery with penicillamine therapy.Therefore it is concluded that neurological feature may be the presenting manifestation of Wilson’s disease even in the absence of clinical evidence of hepatic involvement.