What are the signs and symptoms of Wilson's disease in adolescents?

Signs and Symptoms of Wilson's Disease in Adolescents

Adolescents with Wilson's disease most commonly present with hepatic manifestations (40%), followed by neurological symptoms (35%), and psychiatric disturbances (10%), though these presentations frequently overlap and can be subtle or misdiagnosed as behavioral problems of puberty. 1

Hepatic Manifestations

Liver disease is the predominant presentation in adolescents and can manifest in several ways:

• Asymptomatic hepatomegaly or splenomegaly may be the only finding on physical examination 2
• Persistently elevated aminotransferases (AST, ALT) discovered incidentally during routine testing 2
• Jaundice, anorexia, and vomiting occur in approximately 37-44% of patients presenting with liver disease 1
• Ascites and edema develop in about 23-26% of cases 1
• Acute hepatitis-like presentation that can mimic viral hepatitis 2
• Autoimmune hepatitis-like picture with elevated immunoglobulins and autoantibodies, particularly in those who don't respond to conventional immunosuppressive therapy 1, 2
• Acute liver failure with Coombs-negative hemolytic anemia can occur, representing a life-threatening presentation 2

Hemolytic Manifestations

• Hemolysis occurs in approximately 10-12% of cases and can present as a single acute episode, recurrent episodes, or chronic low-grade hemolysis 1
• Hemolysis may occur with or without clinically evident liver disease 1
• Some adolescents report transient episodes of jaundice in their history, likely representing previous hemolytic episodes 1

Neurological Manifestations

Neurological symptoms typically appear later than hepatic disease but can be the initial presentation in adolescents:

Movement Disorders

• Tremor is characteristic—described as coarse, irregular, proximal tremulousness with a "wing-beating" appearance 1, 2
• Dystonia can be focal, segmental, or severe, involving all body parts and leading to contractures 1
• Akinetic-rigid syndrome resembling Parkinson's disease ("juvenile Parkinsonism") should raise immediate suspicion for Wilson's disease 1
• Ataxia and lack of motor coordination 1, 2

Bulbar and Speech Symptoms

• Dysarthria (slurred speech) is very common and can be cerebellar or extrapyramidal, potentially progressing to aphonia 1
• Drooling is an early and common neurologic symptom 1, 2
• Oropharyngeal dystonia with difficulty swallowing 1
• Facial grimacing, open jaw, running saliva, and lip retraction are characteristic manifestations 1

Fine Motor Changes

• Deteriorating handwriting is an early subtle finding 1, 2
• Micrographia (small, cramped handwriting similar to Parkinson's disease) may develop 1
• Inability to perform activities requiring good hand-eye coordination 1

Psychiatric and Behavioral Manifestations

Approximately one-third of patients initially present with psychiatric abnormalities, and these symptoms frequently precede neurologic or hepatic signs by months to years. 1

Specific to Adolescents

• Declining school performance is often an early warning sign 1, 2
• Personality changes including impulsiveness and labile mood 1, 2
• Inappropriate behavior and sexual exhibitionism 1
• Behavioral changes that are frequently misdiagnosed as normal puberty-related problems 1, 2

General Psychiatric Symptoms

• Depression and anxiety are common 1, 2
• Psychotic features resembling paranoia or schizophrenia can occur 1
• Cognitive function is generally not markedly impaired except in advanced neurological disease 1

Key Diagnostic Physical Finding

• Kayser-Fleischer rings (golden-brownish pigment near the corneal limbus) are present in 90% of patients with neurological manifestations but only 50-62% of those with mainly hepatic disease 2
• Slit-lamp examination by an experienced observer is required for detection, as these rings are usually not visible on routine examination 1, 2
• Absence of Kayser-Fleischer rings does not exclude Wilson's disease, particularly in adolescents presenting primarily with liver disease 1, 2

Less Common Manifestations in Adolescents

• Renal abnormalities including aminoaciduria and nephrolithiasis 1, 2
• Skeletal abnormalities such as premature osteoporosis and arthritis 1, 2
• Cardiomyopathy 1, 2
• Menstrual irregularities in female adolescents 2

Critical Diagnostic Pitfalls

The most dangerous pitfall is misdiagnosing neuropsychiatric symptoms as primary psychiatric disorders or normal adolescent behavioral problems, which can lead to diagnostic delays of up to 12 years. 1, 2

• Attributing declining school performance and behavioral changes solely to puberty without investigating further 1, 2
• Failing to consider Wilson's disease in adolescents with apparent autoimmune hepatitis that doesn't respond to therapy 1, 2
• Mistaking neurologic symptoms for hepatic encephalopathy in patients with advanced liver disease 1
• Not performing slit-lamp examination in patients with unexplained liver or neuropsychiatric symptoms 1, 2

Clinical Approach

Wilson's disease must be excluded in any adolescent with unexplained liver disease, particularly when accompanied by neurological or psychiatric symptoms. 1, 2

• Consider Wilson's disease in any individual aged 3-55 years with liver abnormalities of uncertain cause 1, 2
• Maintain high suspicion in adolescents with declining school performance, behavioral changes, movement disorders, or unexplained hepatitis 1, 2
• Initial evaluation should include slit-lamp examination for Kayser-Fleischer rings, liver function tests, serum ceruloplasmin, and 24-hour urinary copper 1, 2
• Untreated Wilson's disease is universally fatal, making early recognition critical for preventing irreversible morbidity and mortality 1