Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases.

Adenylosuccinate lyase deficiency is an autosomal recessive disorder of purine metabolism resulting from mutations in the ADSL gene on chromosome subband 22q13.1 and associated with a wide range of clinical manifestations. Although there is currently no effective treatment of ADSL deficiency, recognition of the condition is important, because prenatal genetic diagnosis can be offered to affected families. Reported here are the cases of the only three children diagnosed to date in the United Kingdom with adenylosuccinate lyase deficiency, to further delineate the clinical phenotype and to raise awareness of this disorder.

Extracranial internal carotid arterial disease in children with sickle cell anemia.

BACKGROUND: Sickle cell anemia is one of the commonest causes of stroke in children. It is usually, but not always, associated with intracranial vasculopathy. We have assessed the value of ultrasound screening for extracranial internal carotid artery disease. DESIGN AND METHODS: Using Doppler ultrasound scanning, we assessed peak systolic blood velocity, tortuosity and stenosis in the extracranial internal carotid arteries of 236 children with sickle cell anemia. Seventeen of the children had previously had a stroke. All measurements were performed as part of routine clinical care. RESULTS: The median extracranial internal carotid artery velocity was 148cm/s (5(th) centile 84, 95(th) centile 236). Higher velocities were significantly correlated with younger age, higher white blood cell counts and higher rates of hemolysis. Fourteen (5.9%) had tortuous extracranial internal carotid arteries and 13 (5.4%) had stenosis or occlusion. None of the children with tortuous vessels but 8 of those with stenosis had previously had a stroke; the presence of stenosis was strongly associated with overt clinical stroke (OR 35.9, 95% C.I. 9.77-132, P<0.001). In 6 children, extracranial stenosis was part of extensive intracranial vasculopathy, but in 2 there was no evidence of intracranial disease. Stenosis seemed to be more common in older children. CONCLUSIONS: Extracranial internal carotid artery stenosis is strongly associated with stroke in children with sickle cell anemia, and may explain some cases of stroke without overt intracranial vasculopathy. Doppler ultrasound scanning of extracranial internal carotid arteries is non-invasive and fairly quick to perform and may identify children at increased risk of stroke who would otherwise be missed. The value of extracranial internal carotid artery scanning should be studied prospectively.

A simple index using age, hemoglobin, and aspartate transaminase predicts increased intracerebral blood velocity as measured by transcranial Doppler scanning in children with sickle cell anemia.

OBJECTIVE: Increased intracerebral blood velocity measured by transcranial Doppler scanning identifies children with sickle cell anemia who are at increased risk of stroke. We have tried to develop an index based on routine clinical measurements that also predicts increased intracerebral blood flow. METHOD: Routinely collected clinical and laboratory data were correlated with transcranial Doppler measurements on children with sickle cell anemia seen in a single institution in 2006. The index produced was validated on a second independent data set from children with sickle cell anemia. RESULTS: The time-averaged mean of the maximum velocity in centimeters per second in the middle cerebral artery circulation correlated significantly with age, hemoglobin, lactate dehydrogenase, and aspartate transaminase levels, white blood cell count, and creatinine level. On multiple regression, hemoglobin and aspartate transaminase levels maintained their significance, whereas age had borderline significance, and an index was developed linked to a time-averaged mean of the maximum velocity of 220 - (8 x hemoglobin) - (1.4 x age) + (0.4 x aspartate transaminase). This detected a time-averaged mean of the maximum velocity of >170 cm/second with 100% sensitivity and 58% specificity. The index was validated on the second data set and again showed 100% sensitivity with 73% specificity. CONCLUSION: This simple index has the potential to identify children who are at higher risk of cerebrovascular disease to allow them to be prioritized for transcranial Doppler scanning and other intracerebral imaging.

Transcranial Doppler scanning and the assessment of stroke risk in children with HbSC [corrected] disease.

OBJECTIVE: To assess the role of transcranial Doppler (TCD) scanning in assessing the risk of stroke in children with haemoglobin SC (HbSC) disease. TCD scanning has an established role in primary stroke prevention in sickle cell anaemia but its value in HbSC is unknown. DESIGN: A retrospective audit of routinely performed TCD scans and routinely collected clinical data. SETTING: A paediatric sickle cell clinic in a teaching hospital in south London, UK. PATIENTS: 46 children with HbSC disease who have undergone routinely performed TCD scans and steady-state blood tests. MAIN OUTCOME MEASURES: The time-averaged mean of the maximum velocity (TAMMV) in the middle cerebral artery circulation correlated with clinical and laboratory data. RESULTS: The mean TAMMV was 94 cm/s, with a 98(th) centile of 128 cm/s. This is significantly less than the published ranges for HbSS, with a mean reading of 129 cm/s. One child had a stroke at the age of 5 years, when her TAMMV was measured at 146 cm/s. CONCLUSIONS: Further studies are needed to assess stroke risk in HbSC disease, but we suggest that TCD measurements are potentially useful in this condition, and that readings greater than 128 cm/s are abnormally high and warrant further investigation.