New insights into carnitine-acylcarnitine translocase deficiency from 23 cases: Management challenges and potential therapeutic approaches.

Carnitine acyl-carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long-chain fatty-acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi-centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty-three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long-term survival without chronic hyperammonemia. Of the 16 classical cases, 15 had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15), and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 measured) and 14/16 had hypoglycaemia. Nine classical patients survived longer-term-most with feeding difficulties and cognitive delay. Hyperammonaemia appears refractory to ammonia scavenger treatment and carglumic acid, but responds well to high glucose delivery during acute metabolic crises. High-energy intake seems necessary to prevent decompensation. Anaplerosis utilising therapeutic d,l-3-hydroxybutyrate, Triheptanoin and increased protein intake, appeared to improve chronic hyperammonemia and metabolic stability where trialled in individual cases. CACTD is a rare disorder of fatty acid oxidation with a preponderance to severe cardiac dysfunction. Long-term survival is possible in classical early-onset cases with long-chain fat restriction, judicious use of glucose infusions, and medium chain triglyceride supplementation. Adjunctive therapies supporting anaplerosis may improve longer-term outcomes.

Practical approach to the gastrointestinal manifestations of cystic fibrosis.

Cystic fibrosis (CF) is the most common, life-shortening, genetic illness affecting children in Australia and New Zealand. The genetic abnormality results in abnormal anion transport across the apical membrane of epithelial cells in a number of organs, including the lungs, gastrointestinal tract, liver and genito-urinary tract. Thus, CF is a multi-system disorder that requires a multi-disciplinary approach. Respiratory disease is the predominant cause of both morbidity and mortality in patients with CF. However, there are significant and clinically relevant gastrointestinal, liver, pancreatic and nutritional manifestations that must be detected and managed in a timely and structured manner. The aim of this review is to provide evidence-based information and clinical algorithms to guide the nutritional and gastrointestinal management of patients with CF.

Cyproheptadine as an appetite stimulant in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multi-organ genetically inherited disease that leads to progressive lung disease and nutrient malabsorption. The aim of this study was to assess the effectiveness of cyproheptadine (CH) (Periactin®) as an appetite stimulant on improving the nutrition status of paediatric patients with CF. METHODS: We conducted a retrospective study of 15 patients with a suboptimal nutrition status prescribed CH for ≥12 months from 2013 to 2018. Change in Body Mass Index (BMI) z-score and lung function before vs. after treatment with CH were measured as well as dose-response relationship. RESULTS: The mean change in BMI z-score over 12 months of treatment with CH was +0.91 compared to -0.52 in the previous 12 months (p∗∗∗ = 0.0002). There was also a trend towards an improvement in lung function over the 12 months of CH treatment compared to the 12 months prior (+2.79 vs -6.2% (p = 0.07)). No dose-response relationship was observed. CONCLUSION: These results suggest that CH is effective at improving the nutrition status of paediatric CF patients with suboptimal nutrition.

Nutritional Status at Diagnosis, During, and After Treatment in Adolescents and Young Adults with Cancer.

Purpose: Malnutrition is commonly observed during cancer treatment, while some cancer survivors are at risk of overweight and obesity. This study investigated nutritional status during and after treatment in adolescents and young adults (AYA) with cancer. Methods: A retrospective chart review of AYA diagnosed with cancer was conducted. Data were collected monthly during treatment, then annually for 3 years of follow-up. Results: Of 93 AYA, 8% were underweight at diagnosis versus 20% during treatment (p = 0.012). Forty-four percent experienced ≥5% loss of weight (LOW) during treatment, and 23% of those were not referred to a dietitian. While 47% were referred to a dietitian at some point during treatment, 77% did not have dietetic involvement in the month after reaching greatest percentage LOW. Different tumor types were associated with different risks of LOW. Eighty-six percent with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LL) and 86% with acute myeloid leukemia had ≥5% LOW during treatment, compared with 17% with Hodgkin lymphoma (p < 0.0001). In year 3 of follow-up, 36% of all AYA were overweight or obese versus 25% at diagnosis (p = 0.2). Overweight/obesity was more common in ALL/LL survivors than other tumor types (67% vs. 14%, p = 0.037). No patients had dietitian involvement in year 3 of follow-up. Conclusions: AYA, particularly those with ALL/LL, are at risk of significant weight loss during treatment and overweight and obesity during survivorship. Dietetic involvement was inconsistent in this cohort. These data may guide which diagnoses warrant preemptive dietetic input during treatment and highlight the importance of dietetic involvement in survivorship.

Highlights from the nutrition guidelines for cystic fibrosis in Australia and New Zealand.

Optimal nutrition care is important in the management of cystic fibrosis (CF). This paper summarises the '2017 Nutrition Guidelines for Cystic Fibrosis in Australia and New Zealand (NZ)'. CF dietitians formulated 68 practice questions which were used to guide a systematic literature search and review of the evidence for nutrition in CF. Identified papers underwent quality and evidence assessment using the American Dietetic Association quality criteria checklist and the National Health and Medical Research Council of Australia (NHMRC) rankings. Evidence statements, graded recommendations and practice points were developed covering core nutrition topics (assessment and nutrition interventions including oral, enteral and micronutrient supplementation); nutrition-related co-morbidities (including pancreatic insufficiency, CF-related diabetes, bone health and distal intestinal obstruction syndrome); and key new topic areas (genetic modulator therapies, overweight/obesity and complementary therapies). This paper showcases highlights from the guidelines, focussing on new topic areas and geographic and climate considerations for vitamin D, salt and hydration.

Risk of metabolic consequences of rapid weight gain and catch-up growth in the first two years of life: a systematic review protocol.

REVIEW QUESTION: The specific review question to be addressed in this review is: what is the risk of metabolic outcomes for individuals who experience rapid weight gain or catch-up growth during the first two years of life?

Preliminary report of the (13)C-mixed triglyceride breath test to assess timing of pancreatic enzyme replacement therapy in children with cystic fibrosis.

BACKGROUND: Despite guidelines suggesting pancreatic enzyme replacement therapy (PERT) should be taken before or during a meal, it is currently unknown whether this has benefits over administration after a meal in individuals with cystic fibrosis (CF). METHODS: 18 children with pancreatic insufficient CF were randomised to two (13)C-mixed triglyceride ((13)C-MTG) breath tests to assess lipase activity with PERT administered 10min before and 10min after a meal. Results were expressed as percentage cumulative dose recovered (PCDR) of (13)CO2 and were compared with established values in healthy subjects. Gastric half emptying time (T½) was also assessed by a (13)C-octanoate breath test. RESULTS: There was no difference in mean PCDR of (13)CO2 between taking PERT before versus after the meal (p=0.68). Eleven subjects had a greater PCDR when PERT was taken before and 7 when PERT was taken after the meal. 6/8 subjects (75%) with a lower than normal PCDR at one time point normalised PCDR when PERT timing was changed. When PERT was taken after the meal, PCDR was higher in normal vs. fast T½ (p=0.04). CONCLUSIONS: Changing PERT timing can result in normalised lipase activity. Gastric emptying rate may influence optimal timing of PERT. Clinical Trial Registration Number - This study was undertaken prior to the registration process being a commonly required practice.