CASE SUMMARY
A 14-year-old young boy, the third child of non-consanguineous parents presented with multiple joint pain, swelling and fixed deformities for 6 years, difficulty of speech for 6 years and progressive generalized wasting of whole body for 5 years. In the beginning, he had intermittent feverish feeling which was not documented, used to come once or twice daily, each time lasted for 3–4 hours, subsided sometimes spontaneously and sometimes after taking antipyretics. Feverish feeling persisted for almost 1 year. He also had asymmetric, progressive polyarthritis of large and small joints. It started initially with the large joints (at first in right elbow, followed by right shoulder joint and subsequently right hip joint). There was no morning stiffness, no involvement of distal interphalangeal (DIP) joints and never complained of back pain. He developed fixed joint deformities in multiple joints for the last 3–4 years. There was progressive wasting of proximal and distal muscles of all four limbs and trunk, leading him to be completely bedridden for the last 1 year. There was no history of circumoral paresthesia, numbness in hands or feet, craniotabes, dental hypoplasia and no ears, nose and throat (ENT) ailment. Additionally, he had difficulty in speech for the last 6 years; it initially started with slurring, and later on, it deteriorated progressively leading to incomprehensible sounds. Moreover, he had emotional lability with frequent crying bouts for the last 1 year. There was no history of temper tantrums, depression, hyperactivity or disinhibition. There was no history of dysphagia, jaundice, convulsion, bowel and bladder dysfunction. There was no consanguinity of marriage, and family history of similar illness was absent. Multiple consultations were made where he was diagnosed as a case of motor neuron disease.
On examination, he was grossly emaciated, body built was below average, undernourished, irritable with frequent cry and vitals were stable. The GALS screening revealed that gait could not be examined.2
Figs. 1A and B: (A)Torticollis, tortipelvis with swelling and fixed deformity of multiple joints; (B) Gray color ring in the upper part of the limbus.
Arm—dystonia present in both hands, and he had spastic torticollis; legs—on inspection, tortipelvis was present, (Fig. 1A) and multiple joints were swollen, tender and deformed. Fixed deformity was present in both knees and both ankle joints; spine—on inspection from behind scoliosis was present, and spinal movement elicitation was not possible. Examination of the nervous system revealed speech: uttered incomprehensible sounds, intact cranial nerves, muscle bulk were reduced in all four limbs, muscle tone increased, muscle power and reflexes could not be elicited. Plantar responses were flexor bilaterally, sensory function and coordination could not be done appropriately. Examination of the eyes showed the presence of gray colored ring in the upper part of the limbus of both eyes (Fig. 1B). Slit-lamp examination revealed Kayser Fleischer ring in both eyes. Other systemic examination findings were unremarkable.
Investigations showed: Hb level—11.9 g/dL, white blood cells (WBCs)—9,500/cumm (N: 77.8%, L: 18%), platelet (PLT)—393,000/cumm, erythrocyte sedimentation rate (ESR) in first hour—10 mm, urine R/M/E—normal, bedside dipstick test showed trace protein, serum electrolytes—normal, C-reactive protein (CRP)—normal, serum bilirubin—0.93 mg/dL, aspertate aminotransferase (AST)—67 U/L, alanine aminotransferase (ALT)—55 U/L, alkaline phosphatase (ALP)—140 U/L, serum albumin—3.52 g/dL, total protein—7.84 g/dL, corrected calcium—7.5 mg/ dL, serum inorganic phosphate—3.17 mg/dL (normal: 4.7 mg/dL), parathormone—41.2 pg/mL (11–67 pg/mL), spot calcium: creatinine—0.60: 1 (normal: <0.14). Ultrasonography (USG) of W/A—normal. X-ray of chest and upper part of the body posteroanterior view revealed: generalized osteopenia, multiple rib fractures with callus formation in the shaft of fourth to seventh ribs in right side, scoliosis toward left, fracture of right humerus and bilateral shoulder dislocation (Fig. 2A). X-ray of lumbosacral spine anteroposterior and lateral view—severe osteopenia and fracture of neck of left femur; X-ray of wrist joint and hand showed coarse trabeculation.3
Figs. 2A and B: (A) Chest X-ray posteroanterior view showing generalized osteopenia, multiple rib fractures with callus formation in shaft of 4th to 7th rib in right side. Scoliosis towards left with bilateral shoulder dislocation; (B) Magnetic resonance imaging (MRI) of brain showing hyperintensity in bilateral thalamo-ganglionic capsular area.
QUESTIONS
- What is the diagnosis?
- What are the special investigations you need to carry out?
DISCUSSION
For this boy, our differential diagnoses were:
- Juvenile idiopathic arthritis (JIA)
- Rickets
- Wilson's disease.
Some special targeted investigations were carried out to reach the diagnosis: Serum ceruloplasmin—45 mg/dL (normal: 200–600 mg/dL), 24 urinary copper 179 mg/24 hours (>100 mg/24 hours confirms Wilson's disease), magnetic resonance imaging (MRI) of brain showed prominent capsuloganglionic area, ventricles and extraventricular spaces, and hyperintense bilateral thalamo-ganglionic capsular area (Fig. 2B).
Final Diagnosis: Wilson's Disease (Neuropsychiatric and Musculoskeletal Presentation)
The patient's treatment was started with penicillamine and zinc acetate tablets, calcium, vitamin D injection and baclofen tablet. His condition improved remarkably. Within 6 months he was able to walk, and started going to school.
Wilson's disease is a hereditary disorder of the liver and brain. Different types of psychiatric features may be the first presentation of the disease. High index of suspicion is necessary to come up with a straightforward diagnosis.
It rarely presents with musculoskeletal manifestations also when there is accumulation of copper.1 Involvement of large joints, such as knee joint pain, effusion, radiological chondrocalcinosis in young adults and early 4osteoarthritic changes in imaging should be investigated carefully keeping the diagnosis of Wilson's disease in mind. Psychiatric manifestations may precede neurological symptoms of Wilson's disease in 20% of the cases. This patient initially presented with dysarthria and subsequently emotional lability. Afterwards on the basis of significant biochemical abnormalities and the presence of Kayser-Fleischer ring, he was diagnosed as a case of Wilson's disease.
A patient exhibiting neurologic signs or symptoms associated with Kayser-Fleischer rings and ceruloplasmin levels of less than 20 mg/dL confirms a diagnosis of Wilson's disease. Hepatic copper concentration of more than 250 mg/g of dry weight and a low serum ceruloplasmin level are enough to make a diagnosis of hepatic Wilson's disease.2
Chelating agents and medications are used to block copper absorption from the gastrointestinal tract. Zinc and penicillamine are the main treatment options. Trientine, another chelating agent which is more tolerated than penicillamine, can be used. Several other medications are used to combat symptoms, for example, baclofen for dystonia, neuroleptics to treat psychiatric symptoms, levodopa for Parkinsonism and antiepileptics for seizures.
REFERENCES
- Yu H, Xie JJ, Chen YC, Dong Y, Ni WZY. Clinical features and outcome in patients with osseomuscular type of Wilson's disease. BMC Neurol. 2017;17(1):34.
- Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J. Harrison's principles of internal medicine. 20th ed. New York: McGraw Hill Education. 2018. pp. 2982–4.