Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent). Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay), and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts) and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15–18 weeks' gestation, or chorionic villus cells obtained at about 10–12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The lack of precise understanding of the neurological dysfunction has precluded development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation, including management of dysarthria and dysphagia, special devices to enable hand control, appropriate walking aids, and a programme of posture management to prevent deformities are recommended. Self-injurious behaviour must be managed by a combination of physical restraints, behavioural and pharmaceutical treatments

Biomechanical approaches to understanding the potentially injurious demands of gymnastic-style impact landings

<p>Abstract</p> <p>Gymnasts are exposed to a high incidence of impact landings due to the execution of repeated dismount performances. Biomechanical research can help inform recent discussions surrounding a proposed rule change in potentially injurious gymnastic dismounting. The review examines existing understanding of the mechanisms influencing the impact loads incurred in gymnastic-style landings achieved using biomechanical approaches. Laboratory-based and theoretical modelling research of inherent and regulatory mechanisms is appraised. The integration of the existing insights into injury prevention interventions studies is further considered in the appraisals. While laboratory-based studies have traditionally been favoured, the difficulty in controlling and isolating mechanisms of interest has partially restricted the understanding gained. An increase in the use of theoretical approaches has been evident over the past two decades, which has successfully enhanced insight into less readily modified mechanisms. For example, the important contribution of mass compositions and 'tuned' mass coupling responses to impact loading has been evidenced. While theoretical studies have advanced knowledge in impact landing mechanics, restrictions in the availability of laboratory-based input data have suppressed the benefits gained. The advantages of integrating laboratory-based and theoretical approaches in furthering scientific understanding of loading mechanisms have been recognised in the literature. Since a multi-mechanism contribution to impact loading has been evident, a deviation away from studies examining isolated mechanisms may be supported for the future. A further scientific understanding of the use of regulatory mechanisms in alleviating a performer's inherent injury predisposition may subsequently be gained and used to inform potential rule changes in gymnastics. While the use of controlled studies for providing scientific evidence for the effectiveness of gymnastics injury counter measures has been advocated over the past decade, a lack of information based on randomised controlled studies or actual evaluation of counter measures in the field setting has been highlighted. The subsequent integration of insight into biomechanical risk factors of landing with clinical practice interventions has been recently advocated.</p