Question

A 17-year-old girl with multiple complaints is brought to the outpatient clinic by her parents. Her speech and ability to walk have been deteriorating over several months. She has had no recent travel and there is no history of animal bites or known toxic exposures. The patient has a past history of jaundice that occurred 1 year ago. The jaundice persisted for 4 months and then resolved spontaneously. A medical workup at that time did not reveal a clear etiology for the jaundice, and there is no evidence of liver failure. On physical examination, she appears mildly jaundiced but is otherwise well-appearing and in no distress. The ophthalmic examination shows icteric sclera, normal pupillary reactions to light, normal visual acuity and fields, and normal optic fundi. Dark, greenbrown colored rings are noted around the periphery of the iris and are visible on naked eye examination. A neurologic examination reveals slow mentation, slurred speech, diffuse muscle rigidity, and a fine resting tremor. A hepatic panel reveals a total bilirubin of 3.6 mg/dL, an ALT of 99 U/L, an alkaline phosphatase of 284 U/L, an albumin of 4.4 g/dL and a prothrombin time of 18 seconds. Markers for hepatitis B and C are negative

1. What diagnosis is suspected given the finding of the colored rings in her eyes coupled with the patient’s other symptoms?

2. Further laboratory tests were performed. The total serum copper concentration was 55 ug/dL (64-140 ug/dL) with a free fraction value of 27 ug/dL(10-15ug/dL) and the patient was noted to have a low ceruloplasmin level of 12 mg/dL (15-60 mg/dL). A 24-hour urine copper was also markedly elevated at 1708 µg/24 hours (3-35 µg/24 hours). 2. Describe the functions of copper in the body?

Answer 1

1. The above passage gives us the following information regarding the girl patient:

Demographic data: 17-year-old girl

History:

• She has had no recent travel and there is no history of animal bites or known toxic exposures.
• The patient has a past history of jaundice that occurred 1 year ago. Jaundice persisted for 4 months and then resolved spontaneously.
• No clear etiology is known for this jaundice and no evidence of liver failure.

On physical examination

• General appearance
  • Speech and ability to walk have been deteriorating over several months
  • Well appearing with no stress
  • Appears mildly jaundiced
• Ophthalmic examination
  • The icteric sclera, normal pupillary reactions to light,
  • Normal visual acuity and fields
  • Normal optic fundi
  • Dark, green-brown colored rings are noted around the periphery of the iris and are visible on naked eye examination.
• neurologic examination
  • Slow mentation
  • slurred speech
  • Diffuse muscle rigidity
  • Fine resting tremor.
• Lab results:
  • Total bilirubin: 3.6 mg/dL (increased)
  • ALT : 99 U/L (normal)
  • ALP (alkaline phosphatase) : 284 U/L ( increased)
  • Albumin : 4.4 g/dL (increased)
  • Prothrombin time: 18 seconds (increased)
  • Markers for hepatitis B and C: negative

The suspected diagnosis for this patient is Wilson's disease. It is a rare inherited disorder, characterized by the accumulation of copper in the liver brain and other vital organs. Normally copper is absorbed from food and excess amounts of copper are eliminated by the liver through bile. But in patients with Wilson's disease, the excess amount of copper is not eliminated and it keeps on accumulating in other body organs leading to life-threatening conditions. The following findings suggest that the patient is having Wilsons disease:

• She had a history of Jaundice one year back and also a clear etiology was not found in that case. Patients with Wilson's disease have excess amounts of copper present in their liver, which causes impairment in the biliary excretion leading to increased bilirubin level(Jaundice).
• Because of the build-up of copp[er in the nervous system ( brain and spinal cord the patients exhibits the following symptoms :
  • Ability to walk deteriorates
  • Slurred speech
  • Slowed mentation
  • Diffuse muscle rigidity
  • Fine resting tremor.
  • Dark, green-brown colored rings are noted around the periphery of the iris and are visible on naked eye examination: this is one of the classical findings of Wilsons disease. This ring is referred to as Kayser-Fleischer rings, which is formed due to the accumulation of granules rich in copper and sulfur in the Descemet's membrane.
• The lab findings also indicate that patients bilirubin level, ALP, albumin and prothrombin time is increased, also markers for hepatitis B and C were found to be negative: these findings indicate that patient might be suffering from Wilsons disease.

2. The findings of the further laboratory tests are as follows:

• Total serum copper concentration: 55 ug/dL (64-140 ug/dL) ( decreased): Serum copper levels are found to be low in patients with Wilsons disease as the carrier protein ( ceruloplasmin ) levels are decreased in this patient.
• Free fraction value : 27 ug/dL(10-15ug/dL
• Ceruloplasmin level: 12 mg/dL (15-60 mg/dL) ( decreased): Ceruloplasmin is a glycoprotein which carries the copper throughout the body. This level is usually low in patients with Wilsons disease

• 24-hour urine copper: 1708 µg/24 hours (3-35 µg/24 hours) ( markedly high)

Urine copper levels higher than 100 µg/24 hours, is indicative for Wilson's disease.

The presence of Kayser-Fleischer rings, low ceruloplasmin levels and high 24-hour urine copper levels confirms that this girl is diagnosed with Wilson disease

Functions of copper in the body

• Copper along with the iron compound helps to form the red blood cells
• It helps in the brain development during the fetal and also in the post natal period
• Maintains the brain health throughout life
• Promotes wound healing
• Prevents the development of osteoporosis and cardiovascular disorders
• It helps in the proper functioning of the nervous system
• Reduced levels of copper can make more susceptible to infection as the neutrophil levels decrease with decreased copper levels
• It helps to maintain the bone strength by maintaining the bone mineral density
• It acts as an antioxidant agent and prevents skin aging
• It helps in the formation of collagen and elastin in the body and thus prevents skin wrinkling
• It helps to maintain the elasticity of the blood vessels nad thus controls high blood pressure
• Maintain a healthy muscle tone
• Plays a vital role in bone formation and repair