ABSTRACT
Developing objective and quantitative methods of early gross motor assessment is essential to better understand neurodevelopment and to support early therapeutic interventions. Here, we present a method to quantify gross motor performance using a multisensor wearable, MAIJU (Motility Assessment of Infants with a JUmpsuit), which offers an automated, scalable, quantitative, and objective assessment using a fully automated cloud-based pipeline. This wearable suit is equipped with four movement sensors that record synchronized data to a mobile phone utilizing a low-energy Bluetooth connection. An offline analysis in the cloud server generates fully analyzed results within minutes for each recording. These results include a graphical report of the recording session and a detailed result matrix that gives second-by-second classifications for posture, movement, infant carrying, and free playtime. Our recent results show the virtue of such quantified motor assessment providing a potentially effective method for distinguishing variations in the infant's gross motor development.
Subject(s)
Wearable Electronic Devices , Humans , Infant , Motor Skills/physiology , Child Development/physiologyABSTRACT
BACKGROUND: The neonatal screening and early start of the dietary therapy have improved the outcome of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). The acute symptoms of LCHADD are hypoketotic hypoglycemia, failure to thrive, hepatopathy and rhabdomyolysis. Long term complications are retinopathy and neuropathy. Speculated etiology of these long term complications are the accumulation and toxicity of hydroxylacylcarnitines and long-chain fatty acid metabolites or deficiency of essential fatty acids. AIMS: To study the possible development of polyneuropathy in LCHADD patients with current dietary regimen. METHODS: Development of polyneuropathy in 12 LCHADD patients with the homozygous common mutation c.G1528C was evaluated with electroneurography (ENG) studies. The ENG was done 1-12 times to each patient, between the ages of 3 and 40 years. Clinical data of the patients were collected from the patient records. RESULTS: The first sign of polyneuropathy was detected between the ages of 6-12 years, the first abnormality being reduction of the sensory amplitudes of the sural nerves. With time, progression was detected by abnormalities in sensory responses extending to upper limbs, as well as abnormalities in motor responses in lower limbs. Altogether, eight of the patients had polyneuropathy, despite good compliancy of the diet. CONCLUSIONS: This study is the first to report the evolution of polyneuropathy with clinical neurophysiological methods in a relative large LCHADD patient group. Despite early start, and good compliance of the therapy, 6/10 of the younger patients developed neuropathy. However, in most patients the polyneuropathy was less severe than previously described.
Subject(s)
Cardiomyopathies/diet therapy , Cardiomyopathies/genetics , Lipid Metabolism, Inborn Errors/diet therapy , Lipid Metabolism, Inborn Errors/genetics , Mitochondrial Myopathies/diet therapy , Mitochondrial Myopathies/genetics , Mitochondrial Trifunctional Protein/deficiency , Nervous System Diseases/diet therapy , Nervous System Diseases/genetics , Peripheral Nervous System Diseases/etiology , Rhabdomyolysis/diet therapy , Rhabdomyolysis/genetics , Adolescent , Adult , Age Factors , Age of Onset , Child , Child, Preschool , Diet Therapy , Disease Progression , Electrodiagnosis , Electromyography , Female , Follow-Up Studies , Humans , Infant, Newborn , Male , Middle Aged , Mitochondrial Trifunctional Protein/genetics , Mutation/genetics , Neonatal Screening , Patient Compliance , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/physiopathology , Young AdultABSTRACT
AIM: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a severe metabolic disease that, without treatment, often leads to premature death or serious handicap. The aim of this study was to evaluate the clinical course of LCHADD with the homozygous 1528G>C (E510Q) mutation when patients underwent strict dietary treatment. METHODS: From 1997 to 2010, 16 patients with LCHADD were diagnosed in Finland. They were followed up, and data were prospectively collected as they emerged. Clinical data before diagnosis were retrospectively collected from hospital records. This cohort was compared with an earlier cohort of patients diagnosed from 1976 to 1996. RESULTS: The disease presented from birth to five months of age with failure to thrive, hypotonia, hepatomegaly, metabolic acidosis, cardiomyopathy and hypoketotic hypoglycaemia. In this cohort, the therapeutic delay was 0-30 days and the survival rate at the end of the study was 62.5% compared with 10-year survival rate of 14.3% for the earlier cohort. The survivors were in good overall condition, but some of them had developed mild retinopathy or mild neuropathy. CONCLUSION: Earlier diagnosis and stricter dietary regimes improved the survival rates and clinical course of patients with LCHADD in Finland. However, improvements in therapy are still needed to prevent the development of long-term complications, such as retinopathy and neuropathy.
Subject(s)
Cardiomyopathies/diet therapy , Cardiomyopathies/diagnosis , Lipid Metabolism, Inborn Errors/diet therapy , Lipid Metabolism, Inborn Errors/diagnosis , Mitochondrial Myopathies/diet therapy , Mitochondrial Myopathies/diagnosis , Mitochondrial Trifunctional Protein/deficiency , Nervous System Diseases/diet therapy , Nervous System Diseases/diagnosis , Rhabdomyolysis/diet therapy , Rhabdomyolysis/diagnosis , Cardiomyopathies/mortality , Child , Child, Preschool , Early Diagnosis , Female , Finland , Follow-Up Studies , Humans , Infant , Lipid Metabolism, Inborn Errors/mortality , Male , Mitochondrial Myopathies/mortality , Nervous System Diseases/mortality , Prospective Studies , Retrospective Studies , Rhabdomyolysis/mortality , Survival Rate , Treatment OutcomeABSTRACT
OBJECTIVE: Neonatal screening and earlier diagnosis have improved the prognosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency, which causes a need to refine the staging of the pigmentary chorioretinopathy and thus improve monitoring and comparability of patients under dietary therapy. METHODS: Seven children with LCHAD deficiency caused by homozygous G1528C mutation attended sequential fundus photography for stage 2 chorioretinopathy in 19972006. After arranging 21 pairs of fund us photographs according to the severity of the fundus changes,the images best representing 3 different grades of pigmentary deposits (P1P3) and retinal pigment epithelial(RPE) atrophy (A1A3) were chosen as reference photographs.To evaluate the substaging, 29 pairs of photographs were graded according to the reference photographs. RESULTS: In the assessment of pigmentary deposits, the 3 ophthalmologists agreed in 41% and differed by a single substage in 45% of instances (combined weighted ĸ statistic was 0.38, indicating moderate agreement). In pairwise comparisons,the weighted ĸ statistic ranged from 0.31 to 0.56 (agreement, 7181%). In the assessment of RPE atrophy, all 3 raters agreed in 17% and 2 raters in 70% of instances (combined ĸ statistic 0.018, indicating poor agreement). DISCUSSION: Despite variation in imaging techniques and limitations in the visual assessment of fundus photographs, the agreement obtained in grading the pigmentary deposits was comparable to that reported for photographic grading of retinopathy of prematurity. We recommend photographic documentation and substaging based on reference photographs in the follow-up of LCHAD retinopathy. The refined staging allows a more detailed assessment on the progression of the retinopathy and optimization of the therapeutic protocols in individual patients and between centres using different therapeutic protocols.
