[Spinal muscular atrophy : Time for newborn screening?] / Spinale Muskelatrophie : Zeit für das Neugeborenenscreening?

The most common neurodegenerative disease in childhood is spinal muscular atrophy (SMA). The severe infantile type 1 (Werdnig-Hoffman disease) makes 60% of SMA in total. These children usually die within 18 months without ventilation. New therapeutic approaches have led from the theoretical concept to randomized controlled clinical trials in patients. For the first time, a pharmacological treatment of SMA has been approved. The early detection of the disease is decisive for the success of therapy. All previous data suggest starting treatment early and when possible prior to the onset of symptoms considerably improves the outcome in comparison to a delayed start. The goal must be the presymptomatic diagnosis in order to initiate treatment before motor neuron degeneration. Technical and ethical prerequisites for a molecular genetic newborn screening are given.

Mielitis transversa focal posvaricelosa tardía: a propósito de un caso. Revisión y puesta al día / Focal delayed post-chickenpox myelitis. Case report. A review and update

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Genetic testing of sperm donors for cystic fibrosis and spinal muscular atrophy: evaluation of clinical utility.

OBJECTIVE: To evaluate the clinical utility of genetic testing for cystic fibrosis (CF) and spinal muscular atrophy (SMA) in sperm donors. STUDY DESIGN: We studied the results of the genetic tests for CF and SMA applied to 372 sperm donor candidates. The CF carrier screening test analysed 32 mutations on the CFTR gene. Regarding SMA, the carrier test studied possible deletions of SMN1/2 by Multiplex Ligation-dependent Probe Amplification (MLPA) methodology. RESULTS: The carrier frequency obtained was greater for SMA than for CF. After adjusting the results obtained for the sensitivity of the tests, and taking into account the prevalence of female carriers in our population, the probability of transmission of the disease to the child from a donor with a negative genetic test was about five times lower in the case of SMA than in CF, although this difference was not statistically significant. The number of donors needed to screen (NNS) to avoid the occurrence of a child being affected by CF and SMA in our population was similar in both cases (1591 vs. 1536). CONCLUSIONS: This study demonstrates the need to include SMA among the diseases for which genetic screening is performed in the process of sperm donor selection. We believe that testing donors for SMA is as important and as useful as doing so for CF.

Spinal muscular atrophy: a time for screening.

PURPOSE OF REVIEW: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. Even though a specific therapy for SMA is not currently available, a newborn screening test may allow the child to be enrolled in a clinical trial before irreversible neuronal loss occurs and enable patients to obtain more proactive treatments. Until an effective treatment is found to cure or arrest the progression of the disease, prevention of new cases through carrier detection and prenatal diagnosis becomes extremely important. RECENT FINDINGS: The correlation between the SMA phenotype and the SMN2 copy number and the demonstration that sufficient SMN protein from SMN2 in transgenic mice can ameliorate the disease has made the SMN2 gene an obvious target that is being modulated in current therapeutic trials. Most recent work, utilizing gene therapy, has also shown a rescue of the phenotype in the mouse model. Since SMA children are often asymptomatic at birth, newborn screening is a means which will allow the implementation of the most early intervention to take place, before the irreversible loss of motor neurons. Since there is no effective cure for SMA presently, prevention through the identification of carriers becomes an important alternative and has recently been initiated. SUMMARY: Treatment and prevention of SMA are complementary responses to the scourge presented by SMA. This review first describes the molecular genetics of SMA and then focuses on newborn screening, as a means of ensuring the earliest intervention, and the prevention through population carrier screening.

Spinal muscular atrophy (SMA) after conception using gametes from anonymous donors: recommendations for the future.

OBJECTIVE: To discuss the diagnosis of spinal muscular atrophy in a child conceived using donor gametes. DESIGN: None. SETTING: None. PATIENT(S): Offspring of gamete donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): A child conceived using gametes from anonymous sperm and ova donors was diagnosed with spinal muscular atrophy type 1. CONCLUSION(S): Gamete donor facilities are not required to perform extensive genetic testing on their donors; however, the well-being of the children conceived through assisted reproductive technologies should be a primary objective of reproductive medicine. The risk for specific medical problems in donor offspring can be significantly reduced by incorporating carrier screening for common, severe disorders such as spinal muscular atrophy into donor screening practices. Future efforts should focus on communicating the limitations of genetic screening to donor gamete recipients and educating them about their reproductive options.