Clinical spectrum, treatment and outcome of children with suspected diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable chronic disorder of the peripheral nervous system. We retrospectively studied 30 children with a suspected diagnosis of CIDP. The diagnosis of CIDP was compared against the childhood CIDP revised diagnostic criteria 2000. Of the 30 children, five did not meet the criteria and four others met the criteria but subsequently had alternative diagnosis, leaving a total of 21 children (12 male) with CIDP as the final diagnosis. Thirteen children presented with chronic symptom-onset (>8 weeks). The majority presented with gait difficulties or pain in legs (n = 16). 12 children (57%) met the neurophysiological criteria and 18/19 (94%) met the cerebrospinal fluid criteria. Nerve biopsy was suggestive in 3/9 (33%), with magnetic resonance imaging supportive in 9/20 (45%). Twenty-one children received immuno-modulatory treatment at first presentation, of which majority (n = 19, 90%) received IVIG (immunoglobulin) monotherapy with 13 (68%) showing a good response. 8 children received second line treatment with either IVIG or steroids or plasmapharesis (PE) and 4 needed other immune-modulatory agents. During a median follow-up of 3.6 years, 9 (43%) had a monophasic course and 12 (57%) had a relapsing-remitting course. At last paediatric follow up 7 (33%) were off all treatment, 9 (43%) left with no or minimal residual disability and 6 (28%) children were walking with assistance (n = 3) or were non-ambulant (n = 3). Our review highlights challenges in the diagnosis and management of paediatric CIDP. It also confirms that certain metabolic disorders may mimic CIDP.

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.

Intellectual and neurological functioning in Morquio syndrome (MPS IVa).

Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored.