Recurrent Hemolytic Anemia as an Inaugural Manifestation of Wilson Disease in Children : A Case Report

Wilson disease (WD) is a disorder of copper metabolism. Liver and brain disorders are the main presentations, hemolytic anemia in WD is a rare inaugural symptom. We report a case of a child who developed recurrent hemolytic anemia associated with liver failure in the second hemolysis episode as the first manifestation of WD. Wilson's disease is not exceptional in children with hemolytic anemia, but another differential diagnosis must be excluded.


BACKGROUND
Wilson disease is a rare genetic disorder of the copper hepatic metabolism, it results in toxicity due to the accumulation of the mineral.The hemolytic anemia is present in 17% at some point of the disease, although it is a rare initial clinical presentation.

CASE REPORT
An eight-year-old male child, whose parents were consanguineous, two months before he had presented hemolytic anemia only with good outcome after blood transfusion, was referred to our emergency department with generalized oedema and the second episode of hemolytic anemia.
Physical examination revealed a normal growth rate, pallor and mild icterus with facial and legs swelling.Abdominal examination showed ascities, liver and spleen were not palpable.The neurological examination was normal and the Kayser Fleischer ring was not seen on slit lamp examination.His history did not reveal the use of medicine or plants.In addition, there was no similar illness in his three siblings.Initial investigations showed normochromic macrocytic anemia (hemoglobin: 8,7 g/dl MCV:117.3MCH:33)thrombopenia (platelets: 107 000) and 22% of reticulocytes, with a negativecoombs.
His serum electrolytes, urea and creatinine were normal, with a low level of serum albumin: 21.8 g/l and protein serum 59 g/l.An abdominal ultrasound was normal.
A serum sample was returned as having 0,10 g/Lof caeruloplasmin (reference range: 0.15-0.30g/L), using the immunoturbidimetric method, urinary copper 269 µg/24H and a diagnosis of WD was retained.The patient's management consisted of hypercalorichypoproteic diet, and low copper meals.Vitamins, especially vitamin K, and lactulose were achieved.D-penicillamine was introduced progressively.Spironolactone was used to control generalized edema.
The familial screening of WD was normal.
Long-term zinc therapy was started.The improvement of liver function, with a resolution of the prothrombin time was also observed.

DISCUSSION
The age of diagnosis of WD in the majority of patients is between 5 and 35 years [1].About 17% of patients at some point during the natural evolution of WD, may present hemolytic anemia ; it is rare as an initial manifestation [2].
Rarely, Wilson's disease has been detected for the first time during an episode of acute hemolysis [3,5,6].In these circumstances, the hepatic storage capacities of copper are exceeded and it is then liberated massively in the circulation, giving rise of brutal hemolysis, sometimes in the foreground [1].
Hemolytic anemia often disappears and can sometimes recur but the organ toxicity of copper, generally, is the subsequent problem, unless treated.Therefore, any hemolytic episode in a child or young adult should be considered as a case of Wilson's disease unless proven otherwise [7].Among the most frequently found causes, acquired are usually distinguished (autoimmune or immunoallergic hemolytic anemias, Malaria access, microangiopathy thrombotic ...) from constitutional causes (anemia corpuscular, hemoglobinopathies and deficits enzyme) [8].
Of the same, Kitazawa et al. [9] confirmed that a possible diagnosis of WD should be considered in patients presenting a fulminant hepatic failure with signs of Coombs-negative hemolytic anemia.A well-known but delicate presentation of WD is acute or recurrent Coombs-negative hemolytic anemia with or without associated hepatic dysfunction [2].
In the present observation, the first hemolysis episode was isolated, after two months the patient presented the second one associated with an acute liver failure, which made the diagnosis of WD easy.

Laboratory
investigations showed normocyticnormochromic anemia in most reports.ALT was normal, while AST was high in some of the case reports [8, 10 -12].These data disagree with the rest of reviewed case reports where 80% of their cases had elevated ALT and AST.Agrawal et al. [9] in 2011 reported that hemolysis coincides with episodes of low alkaline phosphatase and then improve.While in our case report the anemia was normochromic macrocytic and AST was not very elevated with a normal level of alkaline phosphatase.
A chelating agent(D-penicillamine or trientine) should be prescribed for symptomatic patients until stable.Trientine has fewer side effects, so it may be preferable [13].
The prognosis in Wilson's disease is excellent for patients who receive and are adherent to treatment [13].
After 18 months of progression, the child did not present any side effects of D penicillamine with improvement in liver function.

CONCLUSION
WD is uncommon in children with hemolytic anemia, but other known causes must be excluded.In this case report, we make pediatricians alert about the possibility of the presence of WD in a child over 3 years old with Coombs-negative hemolytic anemia.

Not applicable. HUMAN AND ANIMAL RIGHTS
No animals/humans were used for studies that are the basis of this review.

CONSENT FOR PUBLICATION
A written informed consent was obtained from the parents when they were enrolled.