Delineating the neurological phenotype in children with defects in the ECHS1 or HIBCH gene.

The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres. In total, we analysed the neurological features and mutation spectrum in 19 new SCEH/HIBCH patients. For natural history studies and phenotype to genotype associations we also included 70 previously reported patients. The 19 newly identified cases presented with Leigh syndrome (SCEH, n = 11; HIBCH, n = 6) and paroxysmal dystonia (SCEH, n = 2). Basal ganglia lesions (18 patients) were associated with small cysts in the putamen/pallidum in half of the cases, a characteristic hallmark for diagnosis. Eighteen pathogenic variants were identified, 11 were novel. Among all 89 cases, we observed a longer survival in HIBCH compared to SCEH patients, and in HIBCH patients carrying homozygous mutations on the protein surface compared to those with variants inside/near the catalytic region. The SCEH p.(Ala173Val) change was associated with a milder form of paroxysmal dystonia triggered by increased energy demands. In a child harbouring SCEH p.(Ala173Val) and the novel p.(Leu123Phe) change, an 83.6% reduction of the protein was observed in fibroblasts. The SCEH and HIBCH defects in the catabolic valine pathway were a frequent cause of Leigh syndrome in our cohort. We identified phenotype and genotype associations that may help predict outcome and improve clinical management.

Primary adenosine monophosphate (AMP) deaminase deficiency in a hypotonic infant.

The spectrum of the adenosine monophosphate (AMP) deaminase deficiency ranges from asymptomatic carriers to patients who manifest exercise-induced muscle pain, occasionally rhabdomyolysis, and idiopathic hyperCKemia. However, previous to the introduction of molecular techniques, rare cases with congenital weakness and hypotonia have also been reported. We report a 6-month-old girl with the association of congenital muscle weakness and hypotonia, muscle deficiency of adenosine monophosphate deaminase, and the homozygous C to T mutation at nucleotide 34 of the adenosine monophosphate deaminase-1 gene. This observation indicates the possible existence of a primary adenosine monophosphate deaminase deficiency manifested by congenital muscle weakness and hypotonia.

Comparison of the GlideScope Videolaryngoscope to the standard Macintosh for intubation by pediatric residents in simulated child airway scenarios.

OBJECTIVES: Videolaryngoscopy may facilitate tracheal intubation in difficult airway scenarios. Our objective was to compare the ability of residents to intubate a child manikin using the standard Macintosh laryngoscope and the novel GlideScope. METHODS: Pediatric residents who passed an advanced pediatric life support course were eligible. Four scenarios were proposed: Macintosh (M) and GlideScope (G) "easy" intubation and M and G "difficult"; intubation (cervical immobilization with rigid collar). No participant had previous experience with videolaryngoscope. Each participant performed the 4 scenarios in a random sequence. Time from initiation of intubation procedure to inflation of manikin's chest was recorded, as well as the number of intubation attempts, number of additional maneuvers, dental injury index, and participant's subjective impression. RESULTS: Eighteen subjects were included. Median (range) time for easy airway intubation was 18 seconds (8-120 seconds) with M versus 37 seconds (18-96 seconds) with G (P = 0.029). Time for intubation with cervical immobilization was 19 seconds (9-120 seconds) with M versus 49 seconds (22-120 seconds) with G (P = 0.006). The G intubation in case of cervical immobilization needed significantly more maneuvers than with the M intubation (P = 0.014). There were no significant differences when number of attempts, dental injury index, and participant's subjective difficulty rate were compared. CONCLUSIONS: Without specific training, videolaryngoscope-guided intubation did not improve intubation performance by pediatric residents in this manikin model of normal and simulated difficult intubation caused by a cervical collar in place. To achieve skills with videolaryngoscope intubation in children, a specific training program is needed.