Protein S Deficiency-An Uncommon Cause with Common Presentation

Correction: The correct PDF for this article was loaded on 9th March 2017. We offer our sincere apologies for having the wrong PDF loaded for this article. Stroke in child poses a major health problem. Thrombophilic factors have been implicated in 4-8% of young stroke worldwide. Protein S deficiency is a very rare cause of stroke. A few cases have been reported in literature. We are reporting a rare case of protein S deficiency causing stroke in a two year old child. J Nepal Paediatr Soc 2015;35(2):192-194


Introduction
S troke or cerebro-vascular accident poses a major health problem.Thrombophilic factors have been implicated in 4-8% of young stroke worldwide 1 .Protein S is a naturally occurring vitamin K dependant protein, which in conjunc on with ac ve protein C inhibits the clo ng cascade.Protein S defi ciency is known to be of clinical signifi cance in pa ents with deep venous thrombosis or pulmonary emboli.The incidence of deep vein thrombosis is one episode for every 1000 persons.Protein S defi ciency is found to be associated with cerebro-vascular occlusion, although exact role is controversial.Till now no case has been reported having protein S defi ciency presen ng as proptosis followed by hemiplegia.So we want it to bring into the no ce of every clinician.

The Case
Dipali Tudu, a two year old female child with body weight of 8 kgs was admi ed in our ins tu on with high grade fever for three days and unilateral proptosis of the right eye.She had history of development of furuncle over right side of nose two days before development of fever.There was no contact history of TB.
On examina on, surface temperature was raised (103 o F).Proptosis was no ced on right eye, pupil was normal in size, reac ng normally to light, while le eye was normal on examina on.Heart rate-110/min,Rrespiratory rate -28/min, Blood pressure of 90/60 mmHg.On ausculta on the chest was clear.There were no associated abnormal neurological signs.For Orbital celluli s of right eye and high grade fever, the pa ent was put on intravenous an bio cs, an pyre cs and other suppor ve management.On the second day of admission, pa ent developed le sided complete hemiparesis with UMN type of facial nerve palsy (le ).
IV an bio cs were con nued and aspirin was started along with physiotherapy.Workup for thrombophilias revealed reduced protein S func on 32(50-140), whereas protein C-84 (70-140) and An thrombin III-120(80-120) level were within normal limit.Factor V Leiden muta on, MTHFR gene muta on and Prothrombin gene muta on were not detected.An cardiolipin an body and lupus an coagulant were within normal limits.
During fi rst two weeks of treatment, the pa ent gradually became afebrile and began to walk with support regaining lost power and was ul mately discharged a er about three weeks when the pa ent was able to perform her normal daily ac vi es and was asked to come for follow-up.

Discussion
Stroke in young popula on has a high incidence of approximately 25-35%, according to some studies in India.Abraham et al 2 from Vellore reported an incidence of 25% in popula on less than 40 years of age.Munts et al 3 reported that idiopathic coagula on disorders were found in about a quarter of young stroke pa ents, though there was no clear cut data from India.Carod-A et al 4 studied about ischemic stroke subtypes and prevalence of thrombophilia in Brazilian stroke pa ents.They examined 130 consecu ve young and 200 elderly pa ents.Prevalence of thrombophilia was respec vely: protein S defi ciency (11.5% versus 5.5%), protein C defi ciency (0.76% versus 1%).They drew a conclusion that prothrombo c condi ons were more frequent in of undetermined causes.
The importance of thrombophiolic disorders in arterial stroke has been debatable.Ischemic stroke has been reported as a rare manifesta on of protein S defi ciency.Girolami et al 5 and Sie et al 6 were among the fi rst who reported the associa on of familial defi ciency of protein S as a cause of ischemic stroke in young.Wiesel et al 7 studied 105 pa ents with protein S defi ciency, out of which 14 had arterial thrombo c accidents involving central nervous system or the myocardium, while most studies revealed a weaker associa on between the two 8,9,10 .Douay et al 9 reported that hereditary defi ciencies of coagula on inhibitors are rare in ischemic stroke pa ents under 45 years and their systema c detec on seems to be of poor interest.Mayer et al 8 also supported the fact that acquired defi ciency of free protein S is not a major factor for ischemic stroke.There were only few case reports showing associa on with arterial thrombosis as reported by Ok E J et al 11 .Pantam M et al 12 reported a 20 years old case of protein S defi ciency, presented with homonymous hemianopia and decreased sensa on in right side of the baby.
In this two year old pa ent without any risk factors, the factor S defi ciency possibly played a role for the internal caro d artery thrombosis.Factor S defi ciency should be considered in venous stroke, recurrent pulmonary embolism, unusual site of venous occlusion, family history of vascular events, and stroke in young popula on.Ae ology of such vascular events in young must be thoroughly inves gated so as to guide preven on and treatment of this devasta ng disease.Measurement of total and free protein S levels should be a part of the evalua on for any young adults who has had a stroke.

Conclusion
Therefore when dealing with a case of stroke in children, protein S defi ciency could also be thought of before making proper diagnosis.As protein S defi ciency predisposes to recurrent thrombophilic accidents, long term follow up is required a er diagnosis.Early diagnosis and targeted approach can help such pa ents to prevent recurrent thrombo c episodes.

Table 1 :
Showing results for thrombophilias