Wilson's disease presenting as respiratory failure
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《美国医学杂志》
Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Pondicherry, India
Abstract
Wilson's disease in an 11-year-old girl with generalized weakness and respiratory failure is reported. The child succumbed to severe hypokalemia refractory to therapy progressing to acute renal failure and death. This atypical presentation and course prompted this clinical brief.
Keywords: Wilson′s disease; Respiratory failure; Hypokalemia
Case report
An 11-year-old girl, born to second degree consanguineous parents, presented with inability to use both upper limbs and lower limbs and difficulty in breathing for one day. The child was having low grade fever and vomiting for seven days prior to the sudden onset of the weakness. The parents also gave a history of mild weakness of extremities, slurring of speech and abnormal movements noted during the last two years. On examination she was conscious and oriented with generalized floppiness, mild ptosis, weakness of all four limbs with absent deep tendon reflexes. The breathing was irregular with respiratory muscle weakness. The child had Kayser-Fleicher rings on ophthalmic examination. A diagnosis of Wilson's disease with quadriparesis and impending respiratory failure was made clinically.
At admission, significant hypokalemia (serum potassium 1.8 mEq/L) with normal sodium, urea, calcium and phosphorus were noted. Serum ceruloplasmin of 6 mg/dL, Serum copper 118 μg/dL and 24 hr urinary copper of 79μg/24 hrs confirmed Wilson's disease in her. Her liver function tests were however within normal limits. MRI scan of the brain revealed hypointense signals on T1 and hyperintense signals on T2 in bilateral basal ganglia, thalamus, midbrain and pons. Caudate atrophy was also noted.
The child was given ventilatory support and was started on fluid replacement therapy with added potassium. In spite of adequate fluid therapy, the child was having persistent dehydration and polyuria of >5 ml/kg /hr. She was also noted to have glucosuria and aminoaciduria. In view of these findings, a renal tubular dysfunction secondary to Wilson's disease was suspected.
Within the ensuing 24 hours, the child developed acute renal failure with progressive oligo-anuria, increasing creatinine and hyperkalemia (> 6 m Eq/l) and hypotension. Peritoneal dialysis was started for hyperkalemia refractory to medical therapy. The child did not respond to the above measures, had persistent hypotension and died.
Discussion
This case is of interest due to the presentation of life- threatening hypokalemia in a case of Wilson's disease with neurological features at the young age of 11. The diagnosis of Wilson's disease was initially missed when the child presented with mild weakness, slurring of speech and abnormal movements at the age of 9. Recurrent hypokalemic muscle weakness as an initial manifestation of Wilson's disease was reported from Taiwan in a male patient at the age of 13 by Chu CC et al.[1] Heightened clinical awareness only avoids delay in diagnosis of the appropriate condition.This mode of clinical presentation is of greater significance in the present day context of Acute Flaccid Paralysis Surveillance in our country.[2]
Patients with Wilson's disease can have a variety of renal disturbances. Copper accumulation in the kidneys of patients with Wilson's disease is well known.[3], [4] Proximal tubular dysfunction, decreased glomerular filtration rate and decreased renal plasma flow characterize the resulting renal dysfunction. The common manifestations include proteinuria, glucosuria, phosphaturia, uricosuria, generalized aminoaciduria and microscopic hematuria.[5] Distal renal tubular acidosis and hypercalciuria resulting in nephrocalcinosis is also well- documented.[6] Drugs like penicillamine used in the treatment of Wilson's disease can also result in renal disturbances. Nephrotic syndrome and Good Pasture, like syndrome secondary to Penicillamine therapy has been reported.[7] All patients with renal disturbances except the rare ones with severe irreversible damage will show improvement in renal function with penicillamine therapy.[5] Since the child had not received any prior significant penicillamine therapy, her manifestations are directly attributable to the Wilson's disease itself. Another rare presentation of Wilson's disease common in India is 'osseomuscular' with bony deformities suggestive of renal rickets[8]. Osteomalacia, spontaneous fractures and arthropathy are also seen.[8],[9],[10]
In the patient, the presence of polyuria, glycosuria and aminoaciduria point to a proximal renal tubular dysfunction. The sudden development of renal shut- down within 24 hr despite intensive care is noteworthy. The effect of dehydration and persistent prolonged hypokalemia on dysfunctional renal tubules could have precipitated the acute renal failure in this child. Severe and persistent hypokalemia per se could lead to a variety of renal disturbances like decreased renal blood flow and Glomerular Filtration rate (GFR), defect in renal concentrating capacity etc.[11] There are reports of rhabdomyolysis due to hypokalemia resulting in acute tubular necrosis[12].
Renal disturbances in Wilson's disease, even though well-documented, is rarely the presenting feature and almost never the cause of mortality. This patient had renal disturbances and hypokalemia of unusual severity even before any definitive therapy for Wilson's disease could be started.
In patients presenting with flaccidity and hypokalemia, renal tubular dysfunction due to Wilson's disease should also be considered in the differential diagnosis.
References
1. Chu CC, Huang CC, Chu NS. Recurrent hypokalemic muscle weakness as an initial manifestation of Wilson's disease. Nephron 1996; 73(3) : 477-479.
2. MCH Division, Department of Family Welfare, Ministry of Health and Family Welfare, New Delhi, India. Surveillance of Acute Flaccid Paralysis. 2nd edn. 2000 : 22-23, 35
3. Bearn AG, Yu TF, Gutman Ab. Renal function in Wilson's disease. J Clin Invest 1957; 36 : 1107-1114.
4. Reynolds ES, Tannen Rl, Tyler HR: The renal lesion in Wilson's disease. Am J Med 1966; 40 : 518-527.
5. Leu ML, Strickland Gt, Gutman RA. Renal function in Wilson's disease: Response to Penicillamine therapy. Am J Med Sci 1970; 260 : 381-398.
6. Fulop M, Sternlieb I,Scheinberg IH. Defective urinary acidification in Wilson's disease. Ann Intern Med 1968; 68 : 770-777.
7. Sternlieb I, Bennett B, Scheinberg IH. D-Penicillamine induced Goodpasture's syndrome in Wilson's disease: Ann Intern Med 1975; 82 : 673-676.
8. Pandit A, Bavdekar A, Bhave S. Wilson's disease. Indian J Pediatr 2002; 69 : 785-791.
9. Kalra V, Khurana D, Mittal R. Wilson's disease - Early onset and lessons from a pediatric cohort in India. Indian Pediatr 2000; 37 : 595-601.
10. Sinha S, Jha DK, Sinha KK. Wilson's Disease in Eastern India. J Assoc Physicians India 2001; 49 : 881-884.
11. Tannen RL. Potassium disorders. In Kokko JP, Tannen RL, eds. Fluids and electrolytes. 3rd edn. Philadelphia; W.B. Saunders Company, 1996; 127-129.
12. Nadel SM, Jackson JW, Ploth DW. Hypokalemic Rhabdomyolysis and Acute renal failure. Occurrence following total parenteral nutrition. JAMA 1979; 241 : 2294-2296.(Narayanan P, Chetan G, Ma)
Abstract
Wilson's disease in an 11-year-old girl with generalized weakness and respiratory failure is reported. The child succumbed to severe hypokalemia refractory to therapy progressing to acute renal failure and death. This atypical presentation and course prompted this clinical brief.
Keywords: Wilson′s disease; Respiratory failure; Hypokalemia
Case report
An 11-year-old girl, born to second degree consanguineous parents, presented with inability to use both upper limbs and lower limbs and difficulty in breathing for one day. The child was having low grade fever and vomiting for seven days prior to the sudden onset of the weakness. The parents also gave a history of mild weakness of extremities, slurring of speech and abnormal movements noted during the last two years. On examination she was conscious and oriented with generalized floppiness, mild ptosis, weakness of all four limbs with absent deep tendon reflexes. The breathing was irregular with respiratory muscle weakness. The child had Kayser-Fleicher rings on ophthalmic examination. A diagnosis of Wilson's disease with quadriparesis and impending respiratory failure was made clinically.
At admission, significant hypokalemia (serum potassium 1.8 mEq/L) with normal sodium, urea, calcium and phosphorus were noted. Serum ceruloplasmin of 6 mg/dL, Serum copper 118 μg/dL and 24 hr urinary copper of 79μg/24 hrs confirmed Wilson's disease in her. Her liver function tests were however within normal limits. MRI scan of the brain revealed hypointense signals on T1 and hyperintense signals on T2 in bilateral basal ganglia, thalamus, midbrain and pons. Caudate atrophy was also noted.
The child was given ventilatory support and was started on fluid replacement therapy with added potassium. In spite of adequate fluid therapy, the child was having persistent dehydration and polyuria of >5 ml/kg /hr. She was also noted to have glucosuria and aminoaciduria. In view of these findings, a renal tubular dysfunction secondary to Wilson's disease was suspected.
Within the ensuing 24 hours, the child developed acute renal failure with progressive oligo-anuria, increasing creatinine and hyperkalemia (> 6 m Eq/l) and hypotension. Peritoneal dialysis was started for hyperkalemia refractory to medical therapy. The child did not respond to the above measures, had persistent hypotension and died.
Discussion
This case is of interest due to the presentation of life- threatening hypokalemia in a case of Wilson's disease with neurological features at the young age of 11. The diagnosis of Wilson's disease was initially missed when the child presented with mild weakness, slurring of speech and abnormal movements at the age of 9. Recurrent hypokalemic muscle weakness as an initial manifestation of Wilson's disease was reported from Taiwan in a male patient at the age of 13 by Chu CC et al.[1] Heightened clinical awareness only avoids delay in diagnosis of the appropriate condition.This mode of clinical presentation is of greater significance in the present day context of Acute Flaccid Paralysis Surveillance in our country.[2]
Patients with Wilson's disease can have a variety of renal disturbances. Copper accumulation in the kidneys of patients with Wilson's disease is well known.[3], [4] Proximal tubular dysfunction, decreased glomerular filtration rate and decreased renal plasma flow characterize the resulting renal dysfunction. The common manifestations include proteinuria, glucosuria, phosphaturia, uricosuria, generalized aminoaciduria and microscopic hematuria.[5] Distal renal tubular acidosis and hypercalciuria resulting in nephrocalcinosis is also well- documented.[6] Drugs like penicillamine used in the treatment of Wilson's disease can also result in renal disturbances. Nephrotic syndrome and Good Pasture, like syndrome secondary to Penicillamine therapy has been reported.[7] All patients with renal disturbances except the rare ones with severe irreversible damage will show improvement in renal function with penicillamine therapy.[5] Since the child had not received any prior significant penicillamine therapy, her manifestations are directly attributable to the Wilson's disease itself. Another rare presentation of Wilson's disease common in India is 'osseomuscular' with bony deformities suggestive of renal rickets[8]. Osteomalacia, spontaneous fractures and arthropathy are also seen.[8],[9],[10]
In the patient, the presence of polyuria, glycosuria and aminoaciduria point to a proximal renal tubular dysfunction. The sudden development of renal shut- down within 24 hr despite intensive care is noteworthy. The effect of dehydration and persistent prolonged hypokalemia on dysfunctional renal tubules could have precipitated the acute renal failure in this child. Severe and persistent hypokalemia per se could lead to a variety of renal disturbances like decreased renal blood flow and Glomerular Filtration rate (GFR), defect in renal concentrating capacity etc.[11] There are reports of rhabdomyolysis due to hypokalemia resulting in acute tubular necrosis[12].
Renal disturbances in Wilson's disease, even though well-documented, is rarely the presenting feature and almost never the cause of mortality. This patient had renal disturbances and hypokalemia of unusual severity even before any definitive therapy for Wilson's disease could be started.
In patients presenting with flaccidity and hypokalemia, renal tubular dysfunction due to Wilson's disease should also be considered in the differential diagnosis.
References
1. Chu CC, Huang CC, Chu NS. Recurrent hypokalemic muscle weakness as an initial manifestation of Wilson's disease. Nephron 1996; 73(3) : 477-479.
2. MCH Division, Department of Family Welfare, Ministry of Health and Family Welfare, New Delhi, India. Surveillance of Acute Flaccid Paralysis. 2nd edn. 2000 : 22-23, 35
3. Bearn AG, Yu TF, Gutman Ab. Renal function in Wilson's disease. J Clin Invest 1957; 36 : 1107-1114.
4. Reynolds ES, Tannen Rl, Tyler HR: The renal lesion in Wilson's disease. Am J Med 1966; 40 : 518-527.
5. Leu ML, Strickland Gt, Gutman RA. Renal function in Wilson's disease: Response to Penicillamine therapy. Am J Med Sci 1970; 260 : 381-398.
6. Fulop M, Sternlieb I,Scheinberg IH. Defective urinary acidification in Wilson's disease. Ann Intern Med 1968; 68 : 770-777.
7. Sternlieb I, Bennett B, Scheinberg IH. D-Penicillamine induced Goodpasture's syndrome in Wilson's disease: Ann Intern Med 1975; 82 : 673-676.
8. Pandit A, Bavdekar A, Bhave S. Wilson's disease. Indian J Pediatr 2002; 69 : 785-791.
9. Kalra V, Khurana D, Mittal R. Wilson's disease - Early onset and lessons from a pediatric cohort in India. Indian Pediatr 2000; 37 : 595-601.
10. Sinha S, Jha DK, Sinha KK. Wilson's Disease in Eastern India. J Assoc Physicians India 2001; 49 : 881-884.
11. Tannen RL. Potassium disorders. In Kokko JP, Tannen RL, eds. Fluids and electrolytes. 3rd edn. Philadelphia; W.B. Saunders Company, 1996; 127-129.
12. Nadel SM, Jackson JW, Ploth DW. Hypokalemic Rhabdomyolysis and Acute renal failure. Occurrence following total parenteral nutrition. JAMA 1979; 241 : 2294-2296.(Narayanan P, Chetan G, Ma)