Laronidase seems to be well tolerated and to provide clinical benefit in patients who have severe mucopolysaccharidosis I and are <5 years old. Enzyme replacement therapy is not curative and may not improve all affected organs and systems in individuals when irreversible changes have developed. The long-term clinical outcome and effects of antibodies and laronidase dosing on glycosaminoglycan reduction warrant additional investigation.

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SummaryThis study aimed to investigate whether infants with sickle cell anaemia (SCA) are at risk of neurodevelopmental delay, and whether any delay is associated with SCA pathology. Twenty-eight infants (14 SCA; 14 age-and ethnic-similar controls) were assessed longitudinally with the Bayley Infant Neurodevelopmental Screener (BINS) at 3, 9 and 12 months. Transcranial Doppler (TCD) and pulse oximetry (SpO 2 ) measures were recorded longitudinally in SCA infants, and a subgroup of controls. Haemoglobin values were obtained from SCA infants. At each age, SCA infants obtained BINS scores indicative of greater risk of neurodevelopmental delay compared with controls. The number of moderate-high BINS risk scores increased significantly between 3 and 9 months. At 9 months BINS raw scores correlated negatively with TCD velocity and positively with haemoglobin. This exploratory study suggests that SCA infants may be at greater risk of neurodevelopmental delay than previously considered, and may provide the impetus for further research into the very early precursors of cognitive impairment.

We hypothesized that vaso‐occlusive events in childhood sickle cell disease (SCD) may relate to inflammatory cell activation as well as interactions between sickle erythrocytes and vascular endothelium. Peripheral blood was examined from 24 children with SCD, of whom 12 had neurological sequelae and seven had frequent painful crises, and 10 control subjects. Platelet (CD62P and CD40L expression) and granulocyte (CD11b expression) activation and levels of platelet–erythrocyte and platelet–granulocyte complexes were determined by flow cytometry. Platelets (P = 0·019), neutrophils (P = 0·02) and monocytes (P = 0·001) were more activated and there were increased platelet–erythrocyte complexes (P = 0·026) in SCD patients compared with controls. Platelet–granulocyte complexes were not raised. There were no differences between the different groups of SCD. As hypoxia activates monocytes, platelets and endothelial cells and causes sickling of SCD erythrocytes, we also investigated 20 SCD patients with overnight pulse oximetry. Minimum overnight saturation correlated with the level of platelet–erythrocyte complexes (Spearman's ρ−0·668, P < 0·02), neutrophil CD11b (Spearman's ρ−0·466, P = 0·038) and monocyte CD11b (Spearman's ρ−0·652, P = 0·002). These findings provide important clues about the mechanism by which SCD patients may become predisposed to vaso‐occlusive events.

In children with craniosynostosis, raised intracranial pressure (ICP) and upper airway obstruction (UAO) are both common features. However, potential interactions between UAO and ICP during sleep are poorly understood. The aim of the present study was to compare the levels of ICP during sleep between a group of patients with syndromic craniosynostosis (with facial involvement and consequent UAO) and a group of control patients with isolated unicoronal synostosis (with no facial involvement and normal upper airways).Polygraphic cardiorespiratory sleep studies with continuous monitoring of ICP were performed during unsedated sleep in 13 children with syndromic craniosynostosis and 7 control patients with isolated unicoronal synostosis only.In the syndromic group, UAO was present in 11 out of 13 patients, with 8 out of 13 having frank obstructive sleep apnoea. In contrast, none of the control patients showed signs of UAO during sleep. There was no evidence of central apnoeas in any of the patients studied. Clinical histories taken from parents tended to underestimate the severity of the respiratory problems. Elevated ICP was seen in 10 of the 13 syndromic patients, with borderline raised ICP in the remaining three cases. In contrast, raised ICP was seen in only 3 of the 7 control patients, with borderline raised levels in 2 of the 7. For both patient groups, ICP was higher during active sleep compared to quiet sleep. Multiple regression analysis showed that ICP during active sleep was dependent upon disease severity (unicoronal/multiple synostosis) and to the baseline ICP level during quiet sleep. Both raised ICP and airway obstruction were more apparent during active sleep. There was a significant correlation between severity of UAO and increased ICP in active sleep.We conclude that obstructive respiratory problems are frequent in the syndromic patients, and can be severe in a large proportion of cases; intracranial hypertension is also frequent in this group. Further studies are required to investigate the possibility of a causal relationship between upper airway obstruction and raised intracranial pressure.

Aim-Achondroplasia can result in respiratory diYculty in early infancy. The aim of this study was to document lung growth during infancy, together with the cause of any cardiorespiratory and sleep dysfunction. Patients and methods-Seventeen prospectively ascertained infants (14 boys and three girls) with respiratory symptoms starting before 1 year of age underwent clinical, sleep, and lung function studies. Results-Three distinct groups were identified. Group 1 (n = 6) were the least symptomatic and only had obstructive sleep apnoea. Group 2 (n = 6) had obstructive sleep apnoea of muscular aetiology and, neurologically, hydrocephalus and a small foramen magnum were common. Group 3 (n = 5), the most severely aVected group, all developed cor pulmonale, with three deaths occurring as a result of terminal cardiorespiratory failure. All five had obstructive sleep apnoea with a muscular aetiology (a small foramen magnum predominated) with severe or moderately severe gastrooesophageal reflux. Initially, lung function studies found no evidence of restriction or reduced lung volumes standardised according to weight. However, with growth these infants had worsening function, with raised airway resistance and severe reductions in respiratory compliance. Conclusions-These groups appear to be distinct phenotypes with distinct anatomical aetiologies: "relative" adenotonsillar hypertrophy, resulting from a degree of midfacial hypoplasia (group 1); muscular upper airway obstruction along with progressive hydrocephalus, resulting from jugular foramen stenosis (group 2); and muscular upper airway obstruction, but without hydrocephalus, resulting from hypoglossal canal stenosis with or without foramen magnum compression and no jugular foramen stenosis (group 3). The aetiology of these abnormalities is consistent with localised alteration of chondrocranial development: rostral, intermediary and caudal in groups 1, 2, and 3, respectively. (Arch Dis Child 1998;79:99-108)

We hypothesized that vaso-occlusive events in childhood sickle cell disease (SCD) may relate to inflammatory cell activation as well as interactions between sickle erythrocytes and vascular endothelium. Peripheral blood was examined from 24 children with SCD, of whom 12 had neurological sequelae and seven had frequent painful crises, and 10 control subjects. Platelet (CD62P and CD40L expression) and granulocyte (CD11b expression) activation and levels of platelet-erythrocyte and platelet-granulocyte complexes were determined by flow cytometry. Platelets (P = 0.019), neutrophils (P = 0.02) and monocytes (P = 0.001) were more activated and there were increased platelet-erythrocyte complexes (P = 0.026) in SCD patients compared with controls. Platelet-granulocyte complexes were not raised. There were no differences between the different groups of SCD. As hypoxia activates monocytes, platelets and endothelial cells and causes sickling of SCD erythrocytes, we also investigated 20 SCD patients with overnight pulse oximetry. Minimum overnight saturation correlated with the level of platelet-erythrocyte complexes (Spearman's rho -0.668, P < 0.02), neutrophil CD11b (Spearman's rho -0.466, P = 0.038) and monocyte CD11b (Spearman's rho -0.652, P = 0. 002). These findings provide important clues about the mechanism by which SCD patients may become predisposed to vaso-occlusive events.