Journal of Pediatric Neurosciences
: 2012  |  Volume : 7  |  Issue : 2  |  Page : 157--158

Transient ischemic attack in a child with homocystinuria

K Jagadish Kumar1, S Harsha2, VG Manjunath1, S Mamatha1,  
1 Department of Pediatrics, JSS Medical College, JSS University, Mysore, India
2 Department of Neurology, JSS Medical College, JSS University, Mysore, India

Correspondence Address:
K Jagadish Kumar
Department of Pediatrics, JSS Medical College, JSS University, Mysore, Karnataka

How to cite this article:
Kumar K J, Harsha S, Manjunath V G, Mamatha S. Transient ischemic attack in a child with homocystinuria.J Pediatr Neurosci 2012;7:157-158

How to cite this URL:
Kumar K J, Harsha S, Manjunath V G, Mamatha S. Transient ischemic attack in a child with homocystinuria. J Pediatr Neurosci [serial online] 2012 [cited 2020 Oct 30 ];7:157-158
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Full Text

Dear Sir,

Homocystinuria is a treatable autosomal recessive disorder caused due to cystathionine b-synthase deficiency which affects methionine metabolism. The reported incidence is approximately one in 100,000-200,000 live births. [1] The clinical features are extremely heterogenous, ranging from mental retardation, ectopia lentis, osteoporosis, and vascular events to individuals with no overt clinical picture. [1] The documented vascular events include pulmonary embolism, myocardial infarction, sagittal sinus thrombosis, deep vein thrombosis, and cerebrovascular accidents. [2],[3] Hyperhomocysteinemia is a potent independent major risk factor for vascular disease. [4] Treatment to lower the homocystine levels is effective in reducing the life-threatening vascular risk. [5] We report a child presenting with transient ischemic attack (TIA) as the sole manifestation in the absence of any of the classic phenotypic characteristics of homocystinuria.

A 12-year-old female, born to a non-consanguineous married couple with normal developmental milestones presented with sudden onset of slurring of speech and weakness of right upper and lower limbs since 3h. There was no other significant history or similar episodes in the past.

She was diagnosed with a seizure disorder at the age of 6 years and had taken carbamazepine for 3 years. Family history was unremarkable. On examination, she was afebrile (98.2°F), PR 100/min, RR 20/min, and BP of 118 / 60 mm of Hg. Her anthropometry was normal. There were no marfanoid features or neurocutaneous stigmata. Neurologic examination revealed a conscious alert child (Glascow Coma Scale=15) with motor dysphasia and right hemiparesis. Her cranial nerves, sensory system, spine, and skull examination was normal. Detailed eye examination did not reveal papilledema or lens abnormality. Investigations: Hb 13.1 g/dL, WBC count 12,300/mm 3 (Neutrophils 83%, Lymphocytes 16%) erythrocyte sedimentation rate (ESR) 35 mm, platelets 3.22 lakhs/mm 3 , PCV 38, and normal peripheral blood smear. Her cerebrospinal fluid (CSF) analysis, blood sugar, liver function tests (LFT), blood urea, serum creatinine, serum electrolytes, calcium, phosphorous, fasting lipid profile, and chest X-ray were normal. Her Mantoux test, sickling test, and antinuclear antibody test (ANA) were negative. Her ECG, echocardiography, and color Doppler studies of the carotids were normal. Estimation of phospholipid antibodies (IgM and IgG), cardiolipin antibodies (IgG, IgA, IgM), lupus anticoagulant were normal. Her homocystine levels were elevated i.e. 15.01μmol/L [normal =4.44-13.5μmol/L]. Magnetic resonance imaging (MRI) brain revealed well-defined non-enhancing linear abnormal signal change involving cortex of right frontal lobe measuring 4 mm in thickness and 1.4 cm in length suggestive of an infarct [Figure 1]. Her speech became normal by 3h after admission and weakness of the right limbs disappeared by 6h. Based on the clinical and laboratory results, a diagnosis of homocystinuria was made and treated with aspirin, pyridoxine, folic acid and vitamin B12. She is under follow-up since 5 months without any further vascular events.{Figure 1}

Stroke and cerebrovascular disorders are significant causes of morbidity and mortality in children with annual incidence rates of 2-5 / 100,000 children. [1] Recently, homocysteine has achieved the status of a "hot topic" in vascular disease. [4] Homocystinuria is the second most treatable aminoacidopathy after phenylketonuria. [5] The most common symptoms include neurological complications such as mental retardation and epilepsy, marfanoid features with lens ectopia, and vascular changes represented mostly by thromboembolic events. [2],[5],[6] In a study by Mudd et al. out of 629 homocystinuria patients, only 0.2% of them presented solely as seizures like our case. [2] Homocystinuria is known to be an independent life-threatening risk factor of vascular disease. [4] An increase in plasma homocysteine to 1 SD above the mean is associated with a 60% increase in relative risk for coronary diseases. [3] In a series of 141 stroke children, mild hyperhomocysteinemia was the most frequent risk factor identified. [7] In fact, recently patients with homocystinuria diagnosed solely due to vascular events has been observed. [6] Mudd et al. observed frequent occurrence of vascular events in untreated homocystinuric patients and only 1.1% of their patients manifested solely with a vascular symptom. [2] Our child also presented with classical TIA as a sole manifestation in the absence of any of the classic phenotypic characteristics of homocystinuria. Although homocystinuria as a cause of strokes is well-known, TIA as the initial clinical presentation of homocystinuria is very rare. [3] There is 30% chance of a vascular event before the age of 20 years, which increased to 50% by the age of 30 years. [2] In a series of 629 homocystinuria patients, thromboembolic events were reported in 25% of patients and of these 253 thromboembolic events - 32% of them were cerebrovascular accidents. [2]

Thrombotic and thromboembolic complications are the main causes of morbidity and mortality in homocystinuria. [2],[5] Treatment with vitamin B6 significantly delayed the occurrence of the first thromboembolic event. [8] In a series of 158 homocystinuria patients with 2822 patient-years of treatment, there would be a predicted 112 vascular events if left untreated versus only 17 vascular events with treatment. [3] Treatment to lower the homocysteine levels is effective in reducing the potentially life-threatening vascular risk and therefore, early diagnosis is very important. [3],[4] The mechanism of thrombosis and atherosclerosis due to homocysteinemia is endothelial injury and stimulation of platelet aggregation. [1] The main treatment goal is to decrease the plasma levels of homocysteine by pyridoxine, folate and vitamin B12. [3],[8] Kelly suggested screening for homocystinuria in young adults with stroke without a phenotype suggestive of classic homocystinuria. [9] To conclude, homocystinuria should be considered in the differential diagnosis of cerebrovascular events in children even in the absence of classical phenotype of the disease. We recommend screening for homocystinuria in any child presenting with vascular events, thromboembolic episodes, and also as neonatal screening.


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