Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe?

Glycogen accumulation in the central nervous system of patients with classical infantile onset Pompe disease (IOPD) has been a consistent finding on the few post-mortems performed. While delays in myelination and a possible reduction in processing speed have previously been noted, it has only been recently that the potential for clinically significant progressive white matter disease has been noted. The limited reports thus far published infer that in some IOPD patients, this manifests as intellectual decline in the second decade of life. We present a CRIM negative patient, immunomodulated with rituximab and methotrexate at birth, who despite an initial good clinical response to ERT, at the age of just under 4 years, presented with evolving spasticity in the lower limbs. The investigation of which revealed progressive central nervous system involvement. Given both the earlier onset of the symptoms and consanguineous familial pedigree, extensive biochemical and genetic investigation was undertaken to ensure no alternative pathology was elucidated. In light of these findings, we review the radiology and post-mortems of previous cases and discuss the potential mechanisms that may underlie this presentation.

Successful reversal of propionic acidaemia associated cardiomyopathy: evidence for low myocardial coenzyme Q10 status and secondary mitochondrial dysfunction as an underlying pathophysiological mechanism.

Dilated cardiomyopathy is a rare complication in propionic acidaemia (PA). Underlying pathophysiological mechanisms are poorly understood. We present a child of Pakistani consanguineous parents, diagnosed with late-onset PA at 18months of age. He presented a mild phenotype, showed no severe further decompensations, normal growth and psychomotor development on a low protein diet and carnitine supplementation. At 15years, a mildly dilated left ventricle was noticed. At 17years he presented after a 2-3month history of lethargy and weight loss with severe decompensated dilated cardiomyopathy. He was stabilised on inotropic support and continuous haemofiltration; a Berlin Heart biventricular assist device was implanted. He received d,l-hydroxybutyrate 200mg/kg/day, riboflavin and thiamine 200mg/day each and coenzyme Q10 (CoQ10). Myocardial biopsy showed endocardial fibrosis, enlarged mitochondria, with atypical cristae and slightly low respiratory chain (RC) complex IV activity relative to citrate synthase (0.012, reference range 0.014-0.034). Myocardial CoQ10 was markedly decreased (224pmol/mg, reference range 942-2738), with a marginally decreased white blood cell level (34pmol/mg reference range 37-133). The dose of CoQ10 was increased from 1.5 to 25mg/kg/day. Cardiomyopathy slowly improved allowing removal of the external mechanical cardiac support after 67days. We demonstrate for the first time low myocardial CoQ10 in cardiomyopathy in PA, highlighting secondary mitochondrial impairment as a relevant causative mechanism. According to these findings, a high-dose CoQ10 supplementation could be a potential adjuvant therapeutic to be considered in PA-related cardiomyopathy.

Experience of prehospital emergency care among general practitioners in Ireland.

BACKGROUND: Although widely acknowledged, few data exist on the scope of general practice involvement in the management of prehospital emergencies. A study was undertaken to explore the frequency and types of emergencies dealt with and the interventions undertaken by GPs who had completed Immediate Care training. METHODS: All participants in Immediate Care courses in Ireland in 2002, 2003 and 2004 were invited to complete an anonymised questionnaire in which they estimated their experience of emergencies since completing a course. Sections dealt with personal/practice information, types of emergencies, interventions used and follow-up training. RESULTS: 448 participants completed courses, 408 were available to participate in the study and 259 (63.5%) responded; 66.6% of GPs responded. The mean reporting period was 29.4 months (range 18-53). Participants included many younger female GPs at the start of their general practice careers. Although most emergencies dealt with were medical, few other patterns emerged in the timing or setting of emergencies. 88% of GPs had called an ambulance in an emergency at least once in the preceding year. 84% of GPs had managed a suspected acute myocardial infarction at least once during the reporting period; seizures, serious injuries, paediatric emergencies and hypoglycaemia were dealt with by up to half of all GPs. Interventions used included intravenous access in a medical emergency (69%), intravenous fluid administration (51%), intravenous morphine (54%), cardiopulmonary resuscitation (37%), defibrillation (21%), use of airway adjuncts (28%) and use of advanced life support drugs in cardiac arrest (24%). CONCLUSIONS: GPs make frequent use of a wide range of interventions in prehospital emergencies. Issues relating to tailored training, adequate equipment, collaboration with the emergency services and skills maintenance are highlighted by these data.