GMPPA defects cause a neuromuscular disorder with α-dystroglycan hyperglycosylation.

GDP-mannose-pyrophosphorylase-B (GMPPB) facilitates the generation of GDP-mannose, a sugar donor required for glycosylation. GMPPB defects cause muscle disease due to hypoglycosylation of α-dystroglycan (α-DG). Alpha-DG is part of a protein complex, which links the extracellular matrix with the cytoskeleton, thus stabilizing myofibers. Mutations of the catalytically inactive homolog GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR syndrome), which also involves muscle weakness. Here, we showed that Gmppa-KO mice recapitulated cognitive and motor deficits. As structural correlates, we found cortical layering defects, progressive neuron loss, and myopathic alterations. Increased GDP-mannose levels in skeletal muscle and in vitro assays identified GMPPA as an allosteric feedback inhibitor of GMPPB. Thus, its disruption enhanced mannose incorporation into glycoproteins, including α-DG in mice and humans. This increased α-DG turnover and thereby lowered α-DG abundance. In mice, dietary mannose restriction beginning after weaning corrected α-DG hyperglycosylation and abundance, normalized skeletal muscle morphology, and prevented neuron degeneration and the development of motor deficits. Cortical layering and cognitive performance, however, were not improved. We thus identified GMPPA defects as the first congenital disorder of glycosylation characterized by α-DG hyperglycosylation, to our knowledge, and we have unraveled underlying disease mechanisms and identified potential dietary treatment options.

Nutritional practices in pediatric patients with neuromuscular disorders.

Children with neuromuscular disorders (NMDs) may experience a spectrum of nutritional issues with adverse health consequences. This review summarizes the current understanding of nutritional care in pediatric NMDs, recognizing disease-specific aspects of nutrition alongside the challenges and needs in dietetic care. General or disease-related nutritional issues for children with NMDs include being underweight, overweight, or obese and having swallowing difficulty, gastroesophageal reflux, diarrhea, and/or constipation. Specific challenges in NMD nutritional assessment include alterations in body composition and energy requirements and difficulties in measuring anthropometry. Multidisciplinary dietetic intervention focuses on optimizing nutrient intakes to avert growth failure or obesity and managing feeding difficulties and gastrointestinal problems. Care guidelines are disease specific and vary in approach and detail. To promote best clinical practice across diverse settings, a standardized approach to assessing growth and nutrition across all pediatric NMDs is needed to direct optimal care centered on individual requirements. Future studies should focus on determining the prevalence of specific nutritional issues and the effectiveness of specific interventions among various pediatric NMD populations.

Nutrition management for the patient requiring prolonged mechanical ventilation.

Patients requiring prolonged mechanical ventilation are often medically complex and present with a wide range of pulmonary conditions, including neuromuscular diseases, chronic pulmonary diseases, and chronic critical illness. These patients present the nutrition support professional with many challenges. However, accurate nutrition assessment, timely and effective nutrition interventions, and careful monitoring will help patients meet their medical and nutrition goals.

Avaliação da ingestão alimentar de indivíduos com esclerose lateral amiotrófica / Assessment of dietary intake of individuals with amyotrophic lateral sclerosis / Evaluación de la ingesta dietética de las personas con esclerosis lateral amiotrófica

A esclerose lateral amiotrófica (ELA) caracteriza-se por paralisia progressiva, secundária ao comprometimento de neurônios motores inferiores e superiores. Com a evolução da doença observa-se disfunção motora generalizada e insuficiência respiratória, perda progressiva de peso corporal e alterações na ingestão alimentar. O trabalho teve como objetivo avaliar o consumo alimentar, qualitativo e quantitativo, de pacientes com ELA, acompanhados no setor de Doenças Neuromusculares do HC-UNICAMP. Aplicou-se questionário de freqüência de consumo alimentar e o recordatório de 24 horas, em 23 pacientes. Os alimentos mais consumidos diariamente foram óleo (100%), arroz (96%), leite (96%), feijão (91%) e pão francês (74%). Todos os pacientes apresentaram inadequação para energia, fibras, cálcio e vitamina E. Considerando-se a predominância topográfica do comprometimento muscular na doença, foram observadas diferenças significativas entre pacientes predominantemente bulbares e de predomínio apendicular. Nos pacientes com maior envolvimento apendicular houve maior ingestão energética (p=0,02), de gordura saturada (p=0,03), monoinsaturada (p=0,04) e polinsaturada (p=0,001), além de colesterol (p=0,001) e fibras (p=0,001). Os resultados obtidos permitiram conhecer os hábitos alimentares desta população e estimar a ingestão alimentar. Os dados podem ser aplicados no atendimento nutricional, e orientações específicas poderão proporcionar uma alimentação mais adequada.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive paralysis, secondary to the involvement of upper and lower motor neurons. With disease progression there is widespread motor dysfunction and respiratory failure, progressive loss of body weight and changes in food intake. The study aimed to assess food intake, quality and quantity of ALS patients, accompanied in the field of neuromuscular disorders of the HC-UNICAMP. Questionnaire was used for food frequency and recall of 24 hours in 23 patients. The daily food consumption were oil (100%), rice (96%), milk (96%), beans (91%) and French bread (74%). All patients had inadequate energy, fiber, calcium and vitamin E. Considering the prevalence of topographic affected muscle groups, significant differences were found between predominantly bulbar patients and predominantly appendicular. In patients with greater involvement appendicular energy intake was higher (p = 0.02), saturated fat (p = 0.03), monounsaturated (p = 0.04), polyunsaturated fat (p = 0.001), cholesterol (p = 0.001) and fiber (p = 0.001). The results helped to understand the eating habits of this population and to estimate the dietary intake. The data can be applied in the nutritional intervention, and specific guidelines may provide a more appropriate feeding.

La esclerosis lateral amiotrófica (ELA) se caracteriza por parálisis progresiva, secundaria a la implicación de la parte superior e inferior de las neuronas motoras. Con la progresión de la enfermedad existe disfunción motora generalizada e insuficiencia respiratoria, pérdida progresiva de peso corporal y cambios en la ingesta de alimentos. El objetivo del estudio fue evaluar la ingesta de alimentos, la calidad y la cantidad de pacientes de ELA, acompañado en el campo de los trastornos neuromusculares de la HC-UNICAMP. Se utilizó el cuestionario sobre la frecuencia de alimentos y recordatorio de 24 horas en 23 pacientes. El consumo diario de alimentos fueron aceite (100%), arroz (96%), leche (96%), frijol (91%) y pan francés (74%). Todos los pacientes tenían insuficiencia de energía, fibra, calcio y vitamina E. Teniendo en cuenta la prevalencia de la topográfico grupos musculares afectados, se encontraron diferencias significativas entre los pacientes predominantemente bulbar y predominantemente apendicular. En pacientes con afectación apendicular aumento fue mayor ingesta de energía (p = 0,02), grasa saturada (p = 0,03), monoinsaturados (p = 0,04), grasa poliinsaturada (p = 0,001), colesterol (p = 0,001) y fibra (p = 0,001). Los resultados ayudaron a comprender los hábitos alimentarios de esta población y para estimar la ingesta alimentaria. Los datos pueden ser aplicados en la intervención nutricional, y unas directrices específicas pueden proporcionar una alimentación más adecuada.

High-dose vitamin D supplementation in children with cerebral palsy or neuromuscular disorder.

Adequate vitamin D levels are essential for normal skeletal development and mineralization. This is particularly important in children with cerebral palsy or other neuromuscular disorders who are at an increased risk of osteoporosis. The aim of this study was to evaluate the effect of high-dose vitamin D3 supplementation on vitamin D status in 44 disabled children. Vitamin D was administered during school days (1000 IU vitamin D3 per orally five days per week for 10 weeks) to half of the children (N=21) while the others (N=23) continued without supplementation. At baseline the median serum 25-hydroxyvitamin D was 44 nmol/L (range 26-82 nmol/L). The concentration increased significantly during the 10 weeks intervention in the supplemented group (median 56 nmol/L, range 39-88 nmol/L; p=0.012 for the difference from baseline) and decreased in the control group (median 37 nmol/L, range 24-74 nmol/L; p=0.038). No significant changes in any of the other measured parameters were observed. Hypovitaminosis D is prevalent in disabled children. Supplementation with 1000 IU vitamin D3 perorally five days per week results in a significant increase in vitamin D level and is not associated with hypercalcemia or other adverse effects.

Clinical and pathologic findings in two draft horses with progressive muscle atrophy, neuromuscular weakness, and abnormal gait characteristic of shivers syndrome.

Two Belgian geldings, 4 and 14 years old, respectively, with muscle atrophy, weakness, and abnormal gait characteristic of severe advanced shivers were examined clinically and on necropsy. Neurologic examination revealed no evidence of ataxia, and the clinical diagnosis was neuromuscular weakness and shivers. Necropsies of both horses, including examination of pituitary, brain, spinal cord, spinal roots and ganglia, and peripheral nerves, revealed no gross or histologic abnormalities. Examination of multiple skeletal muscle specimens revealed chronic myopathic changes and periodic acid-Schiff positive, amylase-resistant inclusions within muscle fibers, characteristic of equine polysaccharide storage myopathy. It is suggested that underlying metabolic myopathy may be the cause of muscle weakness and cramping in horses with shivers.

Relation of endometriosis and neuromuscular disease of the gastrointestinal tract: new insights.

OBJECTIVE: To investigate the neuromuscular activity of the gastrointestinal tract by antroduodenal manometry in women with endometriosis documented by laparoscopy, to assess the effects of diet and drug therapy on symptoms, and to assess the bacterial overgrowth that is commonly associated with these nerve diseases. DESIGN: Prospective, open-label study. SETTING: A clinical center for the care of women's health. PATIENT(S): Fifty women with endometriosis documented by laparoscopy and gastrointestinal tract symptoms characterized by chronic abdominal pain, nausea, vomiting, early satiety, bloating and distention, and altered bowel habits. INTERVENTION(S): Motility of the gastrointestinal tract was recorded and bacterial overgrowth was assessed. Treatment consisted of dietary changes, including reduction of glycemic carbohydrates, balancing with omega 9 oils, elimination of foods with caffeine and tyramine, and addition of omega 3 fatty acids, as well as drug therapy with clonazepam (0.25 mg 3 times per day). RESULT(S): All 50 women showed a characteristic motility change (ampulla of Vater-duodenal wall spasm, a seizure equivalent of the enteric nervous system). Forty of the women showed bacterial overgrowth. There was a significant reduction in the total symptom score after 8 weeks of treatment. CONCLUSION(S): This study suggests that endometriosis and gastrointestinal tract symptoms are a result of the dysfunction of hollow organs. Correction of the biochemical imbalance of the eicosanoid system and the hypersecretion of insulin that results from excessive intake of glycemic carbohydrates and lack of essential fatty acids significantly decreases symptoms in patients with endometriosis and associated neuromuscular disease of the gastrointestinal tract.

Autosomal dominant syndrome of lipid neuromyopathy with normal carnitine: successful treatment with long-chain fatty-acid-free diet.

A family (mother and two sons) have had lifelong muscle weakness and intolerance to fatty food. Histochemistry of muscle biopsies of all three patients demonstrated increased lipids in type I muscle fibers and type II muscle fiber atrophy and paucity. Electronmicroscopy of muscle revealed increased lipids, abnormal mitochondria, and increased lipofuscin granules. Electronmicroscopy of sural nerve showed inclusions in most of the Schwann cell cytoplasm, with lipid droplets, zebra bodies, lipofuscin granules, and abnormal mitochondria. Carnitine and CPT I and II levels were normal in serum and muscle. Treatment with long-chain fatty-acid-free diet resulted in remarkable clinical improvement and in decrease of lipid droplets in the muscle. This dietary program may be useful in other forms of lipid myopathy.

Reversal of debrancher deficiency myopathy by the use of high-protein nutrition.

A child with debrancher deficiency presented with myopathy, recurrent hypoglycemia, and growth failure. Evidence for enhanced gluconeogenesis was demonstrated by low postabsorptive gluconeogenic plasma amino acids, a marked fall in alanine during fasting, and a substantial rise in plasma glucose following protein ingestion. The patient was treated with high-protein nocturnal intragastric therapy, which resulted in marked improvement in exercise tolerance, muscle strength and mass, electromyographic findings, and growth.