RESUMO
Arginase deficiency is a rare autosomal recessive urea cycle disorder (UCD) caused by mutations in the ARG1 gene encoding arginase that catalyses the hydrolysis of arginine to ornithine and urea. Patients have hyperargininaemia and progressive neurological impairment but generally suffer fewer metabolic decompensations compared to other UCDs. The objective is to describe the clinical features, biochemical profile, neuroradiological findings and experience of managing children with arginase deficiency. Twenty-year retrospective review of patient medical records at a single metabolic centre was performed. Six patients from three unrelated families were identified. Mean age at first symptom was 3.3 (1.5-9.0) years, while mean age at diagnosis was 8.8 (0.16-15.92) years. Four patients developed spastic diplegia and two of six with spastic quadriplegia with classical features including hyperreflexia, clonus and toe walking. This resulted in gait abnormalities that have been monitored using the GAITRite system and required Achilles tendon release in five children. Generalised tonic-clonic seizures and/or absences were present in three of six children and were controlled with anticonvulsants. All patients had moderate learning difficulties. Neuroimaging showed cerebral/cerebellar atrophy in four patients and basal ganglia abnormalities in two. Arginine levels were universally elevated throughout follow-up despite protein restriction, essential amino acid supplementation and ammonia scavengers, and neurological outcome was generally poor. Two patients died following severe metabolic decompensation in adolescence. Children with arginase deficiency continue to present a management challenge of what appears to be an inexorable course of neurocognitive impairment. Further insight into disease mechanisms may provide insight into novel treatment strategies.
RESUMO
OBJECTIVE: To develop paediatric gait standards in healthy children and young people. METHODS: This observational study aims to address the lack of population standards for gait measurements in children. Analysing gait in children affected by neurological or musculoskeletal conditions is an important component of paediatric assessment but is often confounded by developmental changes. The standards presented here do not require clinician expertise to interpret and offer an alternative to developmental tables of normalised gait data. Healthy children aged 1-19 years were recruited from community settings in London and Hertfordshire, UK. The GAITRite walkway was used to record measurements for each child for velocity, cadence, step length, base of support and stance, single and double support (as percentage of gait cycle). We fitted generalised linear additive models for location, scale and shape (gamlss). RESULTS: We constructed percentile charts for seven gait variables measured on 624 (321 males) contemporary healthy children using a gamlss package in R. A clinical application of gait standards was explored. CONCLUSION: Age-related, gender-specific standards for seven gait variables were developed and are presented here. They have a familiar format and can be used clinically to aid diagnoses and to monitor change over time for both medical therapy and natural history of the condition. The clinical example demonstrates the potential of the Great Ormond Street Institute of Child Health Paediatric Gait Centiles to enable meaningful interpretation of change in an individual's performance and describes characteristic features of gait from a specific population throughout childhood.
