Benign mitochondrial myopathy with exercise intolerance in a large multigeneration family due to a homoplasmic m.3250T>C mutation in MTTL1.

BACKGROUND AND PURPOSE: Most mitochondrial disorders with onset in early childhood are progressive and involve multiple organs. The m.3250T>C mutation in MTTL1 has previously been described in a few individuals with a possibly riboflavin-responsive myopathy and an association with sudden infant death syndrome was suspected. We describe a large family with this mutation and evaluate the effect of riboflavin treatment. METHODS: Medical data were collected with the help of a standardized data collection form. Sanger sequencing was used to screen for variants in mitochondrial DNA and the proportion of the mutation was analyzed in different tissues. Biochemical and muscle morphological investigations of muscle tissue were performed in two individuals. The effect of riboflavin treatment was evaluated in two individuals. RESULTS: Thirteen family members experienced exercise intolerance with fatigue and weakness. Inheritance was maternal with 100% penetrance. The course was either static or showed improvement over time. There was no evidence of other organ involvement except for a possible mild transient cardiac enlargement in one child. Muscle investigations showed isolated complex I deficiency and mitochondrial proliferation. The level of m.3250T>C was apparently 100%, i.e. homoplasmic, in all examined tissues. Riboflavin treatment showed no effect in any treated family member and there have been no cases of sudden infant death in this family. CONCLUSIONS: This study illustrates the importance of considering mitochondrial disorders in the work-up of individuals with exercise intolerance and provides a better understanding of the phenotype associated with the m.3250T>C mutation in MTTL1.

An 18-month follow-up investigation of motor coordination and working memory in primary school children.

The aim of the current study was to examine the relationship between motor coordination and visual working memory in children aged 5-11 years. Participants were 18 children with movement difficulty and 41 control children, assessed at baseline and following an 18-month time period. The McCarron Assessment of Neuromuscular Development provided a measure of motor skills and the CogState One-Back task was used to assess visual working memory. Multi-level mixed effects linear regressions were used to assess the relationship between fine motor skills, gross motor skills, and visual working memory. The results revealed that for children with movement difficulty, better fine motor skills at baseline significantly predicted greater One-Back accuracy and greater (i.e., faster) speed at 18-month follow-up. Conversely, fine motor skills at baseline did not predict One-Back accuracy and speed for control children. However, for both groups, greater One-Back accuracy at baseline predicted better fine and gross motor skills at follow-up. These findings have important implications for the assessment and treatment of children referred for motor difficulties and/or working memory difficulties.

Low motor performance scores among overweight children: poor coordination or morphological constraints?

This study examined whether lower motor performance scores can be full attributed to poor coordination, or whether weight related morphological constraints may also affect motor performance. Data for 666 children and adolescents from the longitudinal Western Australian Pregnancy Cohort (Raine) Study were grouped into normal weight, overweight and obese categories based on the International Obesity Task Force cut points. Participants completed the 10-item McCarron Assessment of Neuromuscular Development (MAND) at the 10 and 14 year follow-up. The prevalence of overweight and obese participants classified with mild or moderate motor difficulties was not different from the normal weight group at 10 years (χ2 = 5.8 p = .215), but higher at 14 years (χ2 = 11.3 p = .023). There were no significant differences in overall motor performance scores between weight status groups at 10 years, but at 14 years, the normal weight group achieved better scores than the obese group (p<.05). For specific items, the normal weight group consistently scored higher than the overweight and obese groups on the jump task at 10 (p<.001) and 14 (p<.01)years but lower on the hand strength task at both ages (p<.01). Our findings raise the question as to whether some test items commonly used for assessing motor competence are appropriate for an increasingly overweight and obese population.

The development of rapid online control in children aged 6-12 years: reaching performance.

Rapid online control during reaching has an important bearing on movement accuracy and flexibility. It is surprising then that few studies have investigated the development of rapid online control in children. In this study, we were particularly interested in age-related changes in the nature of motor control in response to visual perturbation. We compared the performance of younger (6-7 years of age), mid-aged (8-9), and older (10-12) children, as well as healthy young adults using a double-step reaching task. Participants were required to make target-directed reaching movements in near space, while also responding to visual perturbations that occurred at movement onset for a small percentage of trials. Results showed that both the older and mid-aged children corrected their reaching in response to the unexpected shifts in target location significantly faster than younger children, manifest by reduced time to correction. In turn, the responses of adults were faster than older children in terms of movement time and on kinematic measures such as time to correction and time to peak velocity. These results indicate that the capacity to utilize forward estimates of limb position in the service of online control of early perturbations to ballistic (or rapid) reaching develops in a non-linear fashion, progressing rapidly between early and middle childhood, showing a degree of stability over mid and later childhood, but then evidence for continued refinement between childhood and young adulthood. The pattern of change after childhood and into early adolescence requires further investigation, particularly during the rapid phase of physical growth that accompanies puberty.