Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity.

Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p < 0.001). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving z-score value in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.

Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study.

BACKGROUND: The development of both gross and fine motor skills in a child with Down syndrome is generally delayed. The most seriously affected stage is the achievement of independent walking ability, which influences the onset of all following motor and cognitive skills. The study objectives were: 1) to assess the time taken to achieve independent walking ability in a cohort of children with Down syndrome; 2) to examine differences in walking onset by patient characteristics; and 3) to verify the effect of early physical therapy (neurodevelopmental treatment based on Bobath Concept practiced within the first months of life) in the achievement of that skill. METHODS: A retrospective study was carried out on a cohort of 86 children with Down Syndrome. The knowledge of the exact age of walking onset and information about comorbidities and rehabilitation practiced since birth were the eligibility criteria. RESULTS: The average age at which walking began in the sample was 26 months (standard deviation=9.66). Some patient characteristics proved to be related negatively to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity. When practiced, early physical therapy was able to contrast the delay in walking. CONCLUSIONS: NDT-Bobath is a well-known and valid instrument for a child with Down syndrome to attain his highest possible psychomotor functioning level. This study pointed out for the first time ever its capability to contrast the delay on walking onset, which can influence positively the development of the following motor and cognitive skills.

Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria.

The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load. Fourteen phenylketonuric patients aged ≥13 years were enrolled in a 6-week protocol. Oral acute Phe loads of 250 and 500 mg were added to the evening meal together with srLNAAs (0.5 gr/kg). Phe and tyrosine were dosed before dinner, 2h-after dinner, and after the overnight fast. After oral Phe loads, mean plasma Phe remained stable and below 600 µmol/L. No Phe peaks were registered. Tyrosine levels significantly increased, and Phe/Tyrosine ratio decreased. No adverse events were registered. In conclusion, a single oral administration of srLNAAs at the dose of 0.5 gr/kg is effective in maintaining stable plasma Phe during acute oral loads with Phe-containing food and may be added to the dietetic scheme in situations in which patients with generally good adherence to diet foresee a higher than prescribed Phe intake due to their commitments.

Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience.

BACKGROUND: In GM1 gangliosidosis the lack of function of ß-galactosidase results in an accumulation of GM1 ganglioside and related glycoconjugates in visceral organs, and particularly in the central nervous system, leading to severe disability and premature death. In the type 2 form of the disease, early intervention would be important to avoid precocious complications. To date, there are no effective therapeutic options in preventing progressive neurological deterioration. Substrate reduction therapy with Miglustat, a N-alkylated sugar that inhibits the enzyme glucosylceramide synthase, has been proposed for the treatment of several lysosomal storage disorders such as Gaucher type 1 and Niemann Pick Type C diseases. However, data on Miglustat therapy in patients with GM1 gangliosidosis are still scarce. METHODS: We report here the results of Miglustat administration in four Italian children (average age: 55 months, range 20-125) affected by GM1 gangliosidosis type 2 treated in three different Italian pediatric hospitals specialized in metabolic diseases. CONCLUSION: This treatment was safe and relatively well tolerated by all patients, with stabilization and/or slowing down of the neurological progression in three subjects.

Large Neutral Amino Acids (LNAAs) Supplementation Improves Neuropsychological Performances in Adult Patients with Phenylketonuria.

Phenylketonuria is an inborn error of phenylalanine (Phe) metabolism diagnosed by newborn screening and treated early with diet. Although diet prevents intellectual disability, patients often show impairment of executive functions, working memory, sustained attention, and cognitive flexibility. Large neutral amino acids (LNAAs) have been proposed as a dietary supplement for PKU adults. Few studies show that LNAAs may help in improving metabolic control as well as cognitive functions. In this study, 10 adult PKU patients with poor metabolic control were treated for 12 months with LNAAs (MovisCom, 0.8-1 g/kg/day) and underwent Phe and Tyrosine (Tyr) monitoring monthly. Neuropsychological assessment was performed at T0, T+3, and T+12 months by using the American Psychological General Well-Being Index, the Wisconsin Card Sorting Test, the Test of Attentional Performance, and the 9-Hole Peg Test. No change in plasma Phe levels was observed during LNAAs supplementation, while Tyr levels significantly improved during LNAAs supplementation (p = 0.03). Psychometric tests showed an improvement of distress and well-being rates, of executive functions, attention, and vigilance, whereas no difference was noted regarding hand dexterity. This study adds evidence of the advantage of LNAAs supplementation in improving cognitive functions and well-being in patients with PKU with poor metabolic control.