Diagnosis and stabilisation of familial chylomicronemia syndrome in two infants presenting with hypertriglyceridemia-induced acute pancreatitis.

Familial chylomicronemia syndrome (FCS) is a rare disorder of triglyceride (TG) metabolism caused by loss of function variants in one of five known canonical genes involved in chylomicron lipolysis and clearance-LPL, APOC2, APOA5, LMF1, and GPIHBP1. Pathogenic variants in LPL, which encodes the hydrolytic enzyme lipoprotein lipase, account for over 80%-90% of cases. FCS may present in infancy with hypertriglyceridemia-induced acute pancreatitis and is challenging to manage both acutely and in the long-term. Here, we report our experience managing two unrelated infants consecutively diagnosed with hypertriglyceridemia-induced acute pancreatitis caused by LPL deficiency. Both had elevated TGs at presentation (205 and 30 mmol/L, respectively) and molecular genetic testing confirmed each infant carried a different homozygous pathogenic variant in the LPL gene, specifically, c.987C>A (p.Tyr329Ter) and c.632C>A (p.Thr211Lys). The more severely affected infant had cutaneous xanthomata, lipemia retinalis and lipemic plasma at presentation, and required management in an intensive care setting. Acute stabilisation was achieved using insulin and heparin infusions together with the iterative implementation of a fat-restricted diet, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT). In both cases, provision of adequate caloric intake (~110-120 kcal/kg/day) was also found to be important for a sustained TG reduction during the acute phase of management. In summary, a high index of suspicion is required to diagnose FCS in infants with hypertriglyceridemia-induced acute pancreatitis, management of which can be challenging, highlighting the need for more evidence-based recommendations.

Pilot study of a virtual weight management program for Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Young people with Duchenne muscular dystrophy (DMD) are at increased risk of obesity. Weight management is important to families; however, several barriers exist. This pilot study aimed to investigate the feasibility and acceptability of a co-designed weight management program for DMD. METHODS: The Supporting Nutrition and Optimizing Wellbeing Program (SNOW-P) was a single-arm diet and behavior weight management intervention delivered via weekly telehealth/phone visits over 6 weeks to young people with DMD and obesity (body mass index (BMI) ≥95th percentile) and their caregivers. Using an online survey, caregivers of boys with DMD were consulted on the structure and topics delivered in SNOW-P. Primary outcomes were feasibility and acceptability; secondary outcomes were weight, physical function, and quality of life at 6- and 12-weeks follow-up. RESULTS: Of nineteen eligible participants, eight were enrolled (median age 11.4 years, range 4.9-15.8), and seven completed the program. Visit attendance was high (88%-100%); most participants reported high satisfaction and that participation was easy. Suggested changes included online and visual DMD-specific resources. At 6-weeks, median change in weight z-scores was -0.01 (IQR: -0.23, 0.17) indicating that on average, weight gain tracked as expected for age. Waist circumference measured by caregivers lacked accuracy and the completion rate of caregiver-reported secondary outcome measures (e.g., food diaries) was low. DISCUSSION: A co-designed, telehealth/phone weight management program appeared to be feasible and acceptable in a small group of boys with DMD. An adapted, hybrid telehealth and face-to-face program is recommended for efficacy testing.

Exploring caregivers' attitudes and beliefs about nutrition and weight management for young people with Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Obesity disproportionately affects children and adolescents with Duchenne muscular dystrophy (DMD) and with adverse consequences for disease progression. This study aims to: explore barriers, enablers, attitudes, and beliefs about nutrition and weight management; and to obtain caregiver preferences for the design of a weight management program for DMD. METHODS: We surveyed caregivers of young people with DMD from four Australian pediatric neuromuscular clinics. Survey questions were informed by the Theoretical Domains Framework and purposefully designed to explore barriers and enablers to food and weight management. Caregivers were asked to identify their preferred features in a weight management program for families living with DMD. RESULTS: Fifty-three caregivers completed the survey. Almost half (48%) perceived their son as above healthy weight. Consequences for those children were perceived to be self-consciousness (71%), a negative impact on self-esteem (64%) and movement (57%). Preventing weight gain was a common reason for providing healthy food and healthy eating was a high priority for families. Barriers to that intention included: time constraints, selective food preferences, and insufficient nutrition information. Caregivers preferred an intensive six-week weight management program addressing appetite management and screen time. DISCUSSION: Managing weight is an important issue for caregivers of sons with DMD; yet several barriers exist. Individualized 6 week programs are preferred by caregivers to improve weight management for DMD.

The Relationship between Obesity and Clinical Outcomes in Young People with Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder. Young people with DMD have high rates of obesity. There is emerging evidence that a higher BMI may negatively affect clinical outcomes in DMD. This study aimed to explore the relationship between obesity and clinical outcomes in DMD. METHODS: This was a retrospective clinical audit of young people (two-21 years) with DMD. Height and weight were collected to calculate BMI z-scores to classify obesity, overweight and no overweight or obesity (reference category). Cox proportional hazards models determined the impact of obesity at five to nine years on clinical milestones including time to: loss of ambulation, timed function test cut-offs, obstructive sleep apnoea (OSA) diagnosis and first fracture. RESULTS: 158 young people with DMD were included; most (89.9%) were steroid-treated. Mean follow-up was 8.7 ± 4.7 years. Obesity prevalence increased from age five (16.7%) to 11 years (50.6%). Boys with obesity at nine years sustained a fracture earlier (hazard ratio, HR: 2.050; 95% CI: 1.038-4.046). Boys with obesity at six to nine years were diagnosed with OSA earlier (e.g., obesity nine years HR: 2.883; 95% CI: 1.481-5.612). Obesity at eight years was associated with a 10 m walk/run in 7-10 s occurring at an older age (HR: 0.428; 95% CI: 0.207-0.887), but did not impact other physical function milestones. CONCLUSIONS: Although 50% of boys with DMD developed early obesity, the impact of obesity on physical function remains unclear. Obesity puts boys with DMD at risk of OSA and fractures at a younger age. Early weight management interventions are therefore important.

The association between dietary factors and body weight and composition in boys with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a X-linked neuromuscular disorder. Boys with DMD have high rates of obesity, although little is known about dietary factors that may contribute to weight gain in this population. The present study aimed to explore the relationship between dietary factors, body mass index (BMI) z-score, body composition and motor function and to describe dietary intake in boys with DMD. METHODS: A cross-sectional analysis of 3-day food diaries from ambulant and steroid treated boys with DMD aged 5-13 years was conducted. Correlation analysis explored the relationship between dietary factors, BMI z-score, fat mass percentage (FM%) and lean mass percentage (LM%). RESULTS: The median age was 8.5 years (interquartile range [IQR] = 7.2-10.5 years). Median energy kg-1  day-1 in those within a healthy weight range (n = 11) was 316 kJ kg-1  day-1 (IQR = 276-355 kJ kg-1  day-1 ) and greater than estimated requirements and, for those above a healthy weight (n = 26), energy intake was 185 kJ kg-1  day-1 (IQR = 143-214 kJ kg-1  day-1 ) and lower than estimated requirements. Energy kg-1  day-1 was negatively associated with BMI z-score (r = -0. 650) and FM% (r = -0.817) but positively associated with LM% (r = 0.805; all analyses p = <0.01). Younger age was associated (r = -0.609 p = <0.01) with a higher energy kg-1  day-1 . For all participants, vegetable, grains, meat/alternatives and dairy intakes were sub-optimal. CONCLUSIONS: Younger boys with DMD within a healthy weight range are overconsuming energy dense nutrient poor foods. A focus on improving diet quality during early childhood may prove to be a useful strategy for reducing excess weight gain and supporting healthier eating habits in this vulnerable clinical population.

The Validity of Bioelectrical Impedance Analysis to Measure Body Composition in Phenylketonuria.

AIM: To compare the measurement of total body water (TBW) and fat-free mass (FFM) using the criterion method of deuterium dilution space (2H2O) with bioelectrical impedance analysis (BIA) using a portable QuadScan 4000, Bodystat® in children and adolescents with phenylketonuria (PKU). METHODS: Sixteen patients with PKU, median age is 12.5 (range 5-20.6) years, were recruited into this cross-sectional study. TBW was measured by both deuterium dilution and BIA on the same occasion as per a standard protocol. FFM was estimated from predictive equations. RESULTS: There was no significant difference between TBWDeut and TBWBIA (p = 0.344) or FFMDeut and FFMBIA (p = 0.111). TBWDeut and TBWBIA were highly correlated (r = 0.990, p < 0.0001), as were FFMDeut and FFMBIA (r = 0.984, p < 0.0001). Bland-Altman plots demonstrated that there was no proportional bias between the criterion method, TBWDeut, and the test method TBWBIA, in estimating TBW (ß = -0.056, adjusted r 2 = 0.069, p = 0.169) or FFM (ß = -0.089, adjusted r 2 = 0.142, p = 0.083). CONCLUSION: Our results suggest that when compared with the criterion method, the QuadScan 4000, Bodystat® can reliably be used to predict TBW and FFM in patients with PKU. We suggest that due to the portability and non-invasive approach, this method can reliably be used to monitor body composition in the outpatient clinic setting, to further improve the monitoring and assessment of nutritional status in PKU.

The relationship between dietary intake, growth and body composition in Phenylketonuria.

AIM: Phenylketonuria (PKU) is an inborn error of protein metabolism that results from perturbation in phenylalanine hydroxylase activity leading to elevated blood levels of phenylalanine (phe). We aimed to explore the relationships between dietary patterns (total-protein, natural-protein, amino-acid formula), and the ratio of protein to energy intake with growth and body composition. METHOD: Longitudinal prospective data (1-6 measurements) of growth, dietary intake and body composition in patients treated with phe-restricted diet only (D-PKU; n=32), and tetrahydrobiopterin (BH4)±phe-restricted diet (BH4-PKU; n=5) were collected over a two-year period. Healthy siblings provided control data (n=21). RESULTS: There were no significant differences in weight-, height-, BMI z-score or percent body fat mass (%fatmass) between the D-PKU, BH4-PKU and control groups or between the all-types of PKU combined and controls, which confirmed 'normal' growth in the PKU cohort. Total-protein intake in the all-types of PKU group met or exceeded WHO safe protein recommendations. There were no significant relationships between anthropometric and dietary variables. Significant negative correlations were found in body composition: %fatmass and total-protein intake (rs=-0.690, p≤0.001), natural-protein intake (rs=-0.534, p=0.001), and AAF intake (rs=-0.510, p=0.001). Age was significantly correlated with %fatmass (rs=0.493, p=0.002) A total-protein intake of 1.5-2.6g/kg/day and natural-protein intake >0.5g/kg/day were associated with improved body composition. An apparent safe P:E ratio of 3.0-4.5g protein/100kcal was strongly associated with appropriate growth outcomes. CONCLUSIONS: Clinical decision-making needs to consider both the enhancement of natural-protein tolerance and the application of an apparent 'safe' protein to energy ratio to support optimal growth and body composition in PKU.

The Relationship between Dietary Intake, Growth, and Body Composition in Inborn Errors of Intermediary Protein Metabolism.

OBJECTIVES: To examine relationships between dietary intake, growth and body composition patterns in patients with inborn errors of intermediary protein metabolism and to determine a safe protein:energy ratio (P:E ratio) associated with optimal growth outcomes. STUDY DESIGN: Retrospective longitudinal data of growth and dietary intake in patients (n = 75) with isovaleric acidemia (IVA; n = 7), methylmalonic acidemia/propionic acidemia (MMA/PA; n = 14), urea cycle defects (UCD; n = 44), classical maple syrup urine disease (MSUD; n = 10) were collected. Prospective longitudinal data of growth, dietary intake, and body composition from 21 patients: IVA (n = 5), MMA/PA (n = 6), UCD (n = 7), and MSUD (n = 3) were collected at clinic visits. RESULTS: Fifty-two of 75 (66%), 49 of 74 (68%), and 44 of 65 (68%) patients had a z-score of 0 (±1) for lifetime weight, height, and body mass index, respectively. Patients with MMA/PA had the lowest median height and weight z-scores, and MSUD patients had highest median body mass index z-score at all ages. In IVA, MMA/PA, and UCD, total natural protein intake met or exceeded the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO)/United Nations University (UNU) recommended safe levels. Median percentage fat mass was 17.6% in IVA, 20.7% in MMA/PA, 19.4% in UCD, and 17.8% in MSUD. There was a significant negative correlation between percentage fat mass and total protein intake in IVA, MMA/PA, and UCD (r = -0.737; P = .010). The correlation between the P:E ratio and growth variables in IVA, MMA/PA, and UCD suggest a safe P:E ratio (>1.5 to < 2.9) g protein:100 kcal/day. CONCLUSION: Growth outcomes in inborn errors of intermediary protein metabolism are not always ideal. Most patients with IVA, MMA/PA, and UCD consume sufficient natural protein to meet FAO/WHO/UNU recommendations. A P:E ratio range of (>1.5 to < 2.9)g protein/100 kcal/day correlates with optimal growth outcomes.

VLCAD deficiency: Follow-up and outcome of patients diagnosed through newborn screening in Victoria.

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited metabolic disorder of fatty acid oxidation. Treatment practices of the disorder have changed over the past 10-15years since this disorder was included in newborn screening programs and patients were diagnosed pre-symptomatically. A genotype-phenotype correlation has been suggested but the discovery of novel mutations make this knowledge limited. Herein, we describe our experience in treating patients (n=22) diagnosed through newborn screening and mutational confirmation and followed up over a median period of 104months. We report five novel mutations. In 2013 we formalised our treatment protocol, which essentially follows a European consensus paper from 2009 and our own experience. The prescribed low natural fat diet is relaxed for patients who are asymptomatic when reaching age 5years but medium-chain triglyceride oil is recommended before and after physical activity regardless of age. Metabolic stability, growth, development and cardiac function are satisfactory in all patients. There were no episodes of encephalopathy or hypoglycaemia but three patients had episodes of muscle pain with our without rhabdomyolysis. Body composition studies showed a negative association between dietary protein intake and percent body fat. Larger patient cohort and longer follow up time are required for further elucidation of genotype-phenotype correlations and for establishing the role of dietary protein in metabolic stability and long-term healthier body composition in patients with VLCAD deficiency.