Menkes kinky hair disease: A case report

An eight month old male infant with protein energy malnutrition was admitted in the hospital with the history of repeated attacks of convulsion since four months of age. He was also suffering from frequent attacks of cough and cold since 6 months of age which was marked prior to admission. The infant had fair complexion, sparse fuzzy wooly hair with marked trunkal hypotonia. He had also mental retardation. Serum copper and ceruloplasmin levels were low, MRI showed prominent extraaxial spaces with gliosis, MR angiography revealed tortuosity of cerebral vessels. Microscopic examination of hair revealed pili torti. The patient was diagnosed as Menkes disease and treated symptomatically. For lack of facilities we were not able to do genetic study

Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules

Enhancing the robustness of functional biomacromolecules is a critical challenge in biotechnology, which if addressed would enhance their use in pharmaceuticals, chemical processing and biostorage. Here we report a novel method, inspired by natural biomineralization processes, which provides unprecedented protection of biomacromolecules by encapsulating them within a class of porous materials termed metal-organic frameworks. We show that proteins, enzymes and DNA rapidly induce the formation of protective metal-organic framework coatings under physiological conditions by concentrating the framework building blocks and facilitating crystallization around the biomacromolecules. The resulting biocomposite is stable under conditions that would normally decompose many biological macromolecules. For example, urease and horseradish peroxidase protected within a metal-organic framework shell are found to retain bioactivity after being treated at 80 °C and boiled in dimethylformamide (153 °C), respectively. This rapid, low-cost biomimetic mineralization process gives rise to new possibilities for the exploitation of biomacromolecules.Kang Liang, Raffaele Ricco, Cara M. Doherty, Mark J. Styles, Stephen Bell, Nigel Kirby, Stephen Mudie, David Haylock, Anita J. Hill, Christian J. Doonan, Paolo Falcar

MUSCLE ACTIVATION DURING PUSHUPS PERFORMED IN A STABLE AND UNSTABLE ENVIRONMENT IN FEMALE COLLEGIATE SOCCER PLAYERS

Majid M.A. Syed, Dhwani S. Soni, Brittney A. Passini, Palak A. Patel, Robert G. Koeller, Dylan M. Baker, David T. Miller, Thomas J. Pujol, FACSM, Jeremy T. Barnes, Ryan J. Johnson, William M. Miller, Jason D. Wagganer; Southeast Missouri State University, Cape Girardeau, Missouri. Many strength training programs incorporate pushup exercises, which primarily activate upper body muscles. Past data supports the fact that shoulder girdle muscles (i.e., triceps and anterior deltoid) exhibit greater electromyography activity when a push-up is performed on an unstable vs. stable surface (Park, 2011; Andrade, 2011). While greater muscle activation has been shown for healthy athletes (Freeman, 2006), very little research has been conducted on triceps and anterior deltoid muscle activation in lower body trained athletes (i.e. soccer players). Moreover, the majority of past research using EMG analysis has been performed on male athletes (Beach, 2008; Lehman, 2007; Sandhu, 2008; Andrade, 2011). PURPOSE: To determine if differences exist in muscle activation between pushups in a stable vs. unstable environment in female collegiate soccer players. METHODS: Twenty-four female collegiate soccer players (Ht:164.8 ±7.6 cm; Wt:61.7±8.4 kg) participated voluntarily. Subjects had their triceps and anterior deltoid activity assessed using electromyography (EMG) while randomly performing three consecutive regular and three consecutive suspended pushups. A repeated measures (2x2) analysis of variance (ANOVA) was conducted using SPSS (v19.0) to analyze the difference between the triceps and anterior deltoid muscle activation in two push up positions. RESULTS: The absolute integral (AI), which measured electrical activity based upon a standardized baseline, showed significantly higher muscle activation for the unstable compared to the stable push up for the triceps 181.1±227.9 mV (pCONCLUSIONS: The significant increase in muscle activation was attributed to the lack of hand stability incorporated into the unstable push up position. While the female soccer players in this study are well trained, their training regimen primarily activates lower body muscles. These findings provide further support that well-trained one-sport athletes can exhibit increased muscle activation in muscles that are not part of their primary sport focus. Moreover, performing exercises (i.e., pushups) in an unstable environment can effectively increase muscle activation, even for a well-trained female collegiate soccer player

MUSCLE ACTIVATION DURING PUSHUPS PERFORMED IN A STABLE AND UNSTABLE ENVIRONMENT IN FEMALE COLLEGIATE SOCCER PLAYERS

Majid M.A. Syed, Dhwani S. Soni, Brittney A. Passini, Palak A. Patel, Robert G. Koeller, Dylan M. Baker, David T. Miller, Thomas J. Pujol, FACSM, Jeremy T. Barnes, Ryan J. Johnson, William M. Miller, Jason D. Wagganer; Southeast Missouri State University, Cape Girardeau, Missouri. Many strength training programs incorporate pushup exercises, which primarily activate upper body muscles. Past data supports the fact that shoulder girdle muscles (i.e., triceps and anterior deltoid) exhibit greater electromyography activity when a push-up is performed on an unstable vs. stable surface (Park, 2011; Andrade, 2011). While greater muscle activation has been shown for healthy athletes (Freeman, 2006), very little research has been conducted on triceps and anterior deltoid muscle activation in lower body trained athletes (i.e. soccer players). Moreover, the majority of past research using EMG analysis has been performed on male athletes (Beach, 2008; Lehman, 2007; Sandhu, 2008; Andrade, 2011). PURPOSE: To determine if differences exist in muscle activation between pushups in a stable vs. unstable environment in female collegiate soccer players. METHODS: Twenty-four female collegiate soccer players (Ht:164.8 ±7.6 cm; Wt:61.7±8.4 kg) participated voluntarily. Subjects had their triceps and anterior deltoid activity assessed using electromyography (EMG) while randomly performing three consecutive regular and three consecutive suspended pushups. A repeated measures (2x2) analysis of variance (ANOVA) was conducted using SPSS (v19.0) to analyze the difference between the triceps and anterior deltoid muscle activation in two push up positions. RESULTS: The absolute integral (AI), which measured electrical activity based upon a standardized baseline, showed significantly higher muscle activation for the unstable compared to the stable push up for the triceps 181.1±227.9 mV (pCONCLUSIONS: The significant increase in muscle activation was attributed to the lack of hand stability incorporated into the unstable push up position. While the female soccer players in this study are well trained, their training regimen primarily activates lower body muscles. These findings provide further support that well-trained one-sport athletes can exhibit increased muscle activation in muscles that are not part of their primary sport focus. Moreover, performing exercises (i.e., pushups) in an unstable environment can effectively increase muscle activation, even for a well-trained female collegiate soccer player

Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I

Diagnosis and management of glutaric aciduria type I - revised recommendations

Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline

Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)

Glutaryl-CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the disease is characterized by accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatography-mass spectrometry of organic acids or tandem mass spectrometry of acylcarnitines. Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and, subsequently, dystonia. During the last three decades attempts have been made to establish and optimize therapy for GCDH deficiency. Maintenance treatment consisting of a diet combined with oral supplementation of L-carnitine, and an intensified emergency treatment during acute episodes of intercurrent illness have been applied to the majority of patients. This treatment strategy has significantly reduced the frequency of acute encephalopathic crises in early-diagnosed patients. Therefore, GCDH deficiency is now considered to be a treatable condition. However, significant differences exist in the diagnostic procedure and management of affected patients so that there is a wide variation of the outcome, in particular of pre-symptomatically diagnosed patients. At this time of rapid expansion of neonatal screening for GCDH deficiency, the major aim of this guideline is to re-assess the common practice and to formulate recommendations for diagnosis and management of GCDH deficiency based on the best available evidence

Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency

Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare inborn disorder Of L-lysine, L-hydroxylysine, and L-tryptophan metabolism complicated by striatal damage during acute encephalopathic crises. Three decades after its description, the natural history and how to treat this disorder are still incompletely understood. To study which variables influenced the outcome, we conducted an international cross-sectional study in 35 metabolic centers. Our main outcome measures were onset and neurologic sequelae of acute encephalopathic crises. A total of 279 patients (160 male, 119 female) were included who were diagnosed clinically after clinical presentation (n = 218) or presymptomatically by neonatal screening (n = 23), high-risk screening (n = 24), or macrocephaly (n = 14). Most symptomatic patients (n = 185) had encephalopathic crises, characteristically resulting in bilateral striatal damage and dystonia, secondary complications, and reduced life expectancy. First crises usually occurred during infancy (95% by age 2 y); the oldest age at which a repeat crisis was reported was 70 mo. In a few patients, neurologic disease developed without a reported crisis. Differences in the diagnostic criteria and therapeutic protocols for patients with GCDH deficiency resulted in a huge variability in the outcome worldwide. Recursive partitioning demonstrated that timely diagnosis in neurologically asymptomatic patients followed by treatment with L-carnitine and a lysine-restricted diet was the best predictor of good outcome, whereas treatment efficacy was low in patients diagnosed after the onset of neurologic disease. Notably, the biochemical phenotype did not predict the clinical phenotype. Our study proves GCDH deficiency to be a treatable disorder and a good candidate for neonatal screening