Suresh Vijay

The micronutrient status of patients with phenylketonuria on dietary treatment: an ongoing challenge.

Background: In phenylketonuria (PKU), phenylalanine-free L-amino acid supplements are the major source of dietary micronutrients. Methods: Four hundred fifty-two retrospective annual/bi-annual non-fasting blood samples for nutritional markers (plasma zinc, selenium, and serum folate) from 78 subjects aged 1-16 years (median number of blood samples: 6, range 1-14) were analysed over 12 years. Longitudinal blood result data were available for 51 subjects (65%). The dietary intake from supplements was calculated. Results: The median intakes of all of the micronutrients studied were >200% of the reference nutrient intakes (RNI). There was no statistical correlation between dietary intake and nutritional markers outside of the normal reference range (RR) except for selenium, but there was a correlation between a lower plasma zinc, plasma selenium and haemoglobin status and better blood phenylalanine control in 1- to 4-year-old children. On at least one occasion, the individual plasma concentrations of zinc (71%, n = 54/76) and selenium (21%, n = 16/75) were below the RR; however, the concentrations of selenium (41%, n = 31/75) and serum folate (83%, n = 34/41) were also above the RR. Dietary intakes exceeded the upper tolerable intakes for zinc and copper (32%, n = 25) and folate (65%, n = 51). Individual longitudinal data demonstrated little change in micronutrient status over time. Conclusions: In PKU, biochemical micronutrient deficiencies are common despite micronutrient intakes above the RNI. Further study of the nutritional profiling of L-amino acid supplements in PKU is needed.

The challenges of vitamin and mineral supplementation in children with inherited metabolic disorders: a prospective trial

BACKGROUND In order to achieve metabolic stability, dietary treatment of inborn errors of metabolism may require restriction of protein, fat or carbohydrate. Manipulation of dietary intake potentially reduces micronutrient status, and provision of a comprehensive vitamin and mineral supplement becomes an essential adjunct to dietary treatment. AIM To review the efficacy of a new complete vitamin and mineral supplement [Fruitivits, Vitaflo Ltd] in 14 subjects in an open prospective 26-week study. METHOD All subjects had dietary restrictions: low protein diets (57%, n = 8), regular daytime cornstarch and overnight glucose polymer tube feeds (29%, n = 4), low fat diet (7%, n = 1) and modified Atkins diet (7%, n = 1). Plasma nutritional biochemistry, anthropometry and food frequency questionnaires were collected at week 0, 12 and 26 weeks respectively. RESULTS Five nutritional parameters showed a significant improvement from baseline (week 0) to study end (week 26): folate (P = 0.01), vitamin E (P = 0.04), plasma selenium (P = 0.002), whole blood selenium (P = 0.04) and total vitamin D (P = 0.008). All the other nutritional markers did not significantly change. Even with regular monitoring, 37% of the product remained unused. CONCLUSIONS Despite improvements in some nutritional markers, overall use of the vitamin and mineral supplement was less than prescribed. New methods are needed to guarantee delivery of micronutrients in children at risk of deficiencies as a result of an essential manipulation of diet in inborn disorders of metabolism.

The safety of Lipistart, a medium-chain triglyceride based formula, in the dietary treatment of long-chain fatty acid disorders: a phase I study

Abstract Background: Children with long-chain fatty acid β-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children. Methods: In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7–13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored. Results: Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500–1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed. Conclusions: This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.

Oculomotor abnormalities in children with Niemann-Pick type C

Niemann-Pick type C (NP-C) is a rare recessive disorder associated with progressive supranuclear gaze palsy. Degeneration occurs initially for vertical saccades and later for horizontal saccades. There are studies of oculomotor degeneration in adult NP-C patients [1, 2] but no comparable studies in children. We used high-resolution video-based eye tracking to record monocular vertical and horizontal eye movements in 2 neurological NP-C patients (children with clinically observable oculomotor abnormalities) and 3 pre-neurological NP-C patients (children without clinically observable oculomotor abnormalities). Saccade onset latency, saccade peak velocity and saccade curvature were compared to healthy controls (N=77). NP-C patients had selective impairments of vertical saccade peak velocity and vertical saccade curvature, with slower peak velocities and greater curvature. Changes were more pronounced in neurological than pre-neurological patients, showing that these measures are sensitive to disease progress, but abnormal curvature and slowed downward saccades were present in both groups, showing that eye-tracking can register disease-related changes before these are evident in a clinical exam. Both slowing, curvature and the detailed characteristics of the curvature we observed are predicted by the detailed characteristics of RIMLF population codes. Onset latencies were not different from healthy controls. High-resolution video-based eye tracking is a promising sensitive and objective method to measure NP-C disease severity and neurological onset. It may also help evaluate responses to therapeutic interventions.

How to use a controlled fast to investigate hypoglycaemia

Controlled fasts can play a valuable role in the diagnosis and management of hypoglycaemia in paediatric clinical practice, but are no substitute for the collecting of appropriate critical samples at the time of hypoglycaemia for metabolic and endocrine studies. Fatty acid oxidation defects, hyperinsulinism and adrenal insufficiency should always be excluded prior to organising controlled fasts. Controlled fasts are safe if conducted in an experienced setting with strict protocols in place. Failure to adhere to protocol can defeat the purpose of the study and can potentially be dangerous. Proper planning in conjunction with the laboratory and close supervision by staff experienced in controlled fasts is crucial to ensure the best quality information is yielded from these procedures.

Clinical presentation and follow-up of patients with the attenuated phenotype of mucopolysaccharidosis type I: Clinical features in attenuated mucopolysaccharidosis I

Aim: To review the heterogeneity and severity of the clinical features at the attenuated end of the mucopolysaccharidosis (MPS) type I disease spectrum. Methods: The course of disease in 29 patients with attenuated mucopolysaccharidosis I who attended the MPS clinic in Manchester, UK, was reviewed. Results: For more than half of the patients, onset of symptoms was in the first 2 y of life, and the age at diagnosis ranged from 15 mo to 40 y. Joint stiffness, corneal clouding, umbilical hernia and recurrent ear, nose and throat symptoms were the commonest features at presentation. Patients experienced significant morbidity during the course of this inherited disease. Skeletal problems predominated and cardiac valve pathology, upper airway obstruction and hearing deficits were detected in a notable number of patients. Nerve decompression for carpal tunnel syndrome, cervical cord decompression, and grommet insertion for serous otitis media were the most frequent surgical interventions.