Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Germany, Austria: Friedrich-Baur-Institut, Medizinische FakultГ¤t der Ludwig-Maximilians-UniversitГ¤t MГјnchen, Europe: TREAT-NMD Network Further innovative experimental treatment approaches are in development and new treatments are anticipated ( Govoni A et al). In these therapies, the mutated SMN1 gene is replaced through an adeno-associated virus vector incorporating the SMN1 gene producing SMN proteins. Another pilot study including infants with SMA-type I presented neuromuscular improvements after single dose of an intravenous applied gene-replacement therapy ( Mendell JR et al). Half of the affected individuals with early onset (infantile) SMA showed an improvement motor skills and increased survival rate without severe adverse reactions. Repeated injections are applied intrathecally and leads to increased production of SMN proteins by the SMN2 genes ( Finkel RS et al). Nusinersen is a new antisense oligonucleotide treatment for standard care. In Europe, a medicinal product Nusinersen, used to treat 5q-associated SMA in pediatric and adult affected persons, has been approved. Fasciculation of the muscle especially legs und upper arms.Diagnostics for SMA are recommended with the following clinical manifestations. Symptoms for late onset forms of SMA are similar to Early onset forms typically in milder presentations.

Reduced fetal movements during pregnancy muscular hypotonia (proximal, symmetric) or muscular weakness of unknown origin.ДЄny occurrence of muscular hypotonia, chronic cough, feeding difficulties, reflux, recurrent vomiting and respiratory infectionsД«y 3 months of life вЂ“ cannot hold the head up from the baseД«y 5 months of life вЂ“ no head control in upright positionД«y 10 months of life вЂ“ no sitting unassistedД«y 17 months of life вЂ“ no standing unassistedД«y 19 months of life вЂ“ no walking unassisted.Diagnostics for SMA are recommended in the following scenarios (See also Table 1): Developmental milestones will not be reached or already acquired skills are disappearing. Typical symptoms for early onset (infantile) SMA is symmetric, proximal impairment with muscular hypotonia and weakness, reduced or absent reflexes, legs are affected more than arms. These diagnostic tools offer the opportunity of a feasible prevention program like in newborn screening or with suspected cases like infants with muscular hypotonia or a rather floppy infant. Today, efficient and specific diagnostic tests for SMA are available. An early diagnosis of affected newborns is important ( Chien YH et al) because this enables an adequate drug or therapy intervention at an early stage, even before clinical manifestation ( Finkel et al, Mendell et al). Experts suggest primary molecular genetic testing for faulty SMN1 genes in cases of suspected SMA ( TREAT-NMD). At present, only a carrier screening is recommended (ACOG, Muralidharan K et al, Boardman FK et al).

SMA diagnosis typically occurs from four to 44 months of life ( Lin CW et al). For early onset SMA, clinical symptoms begin at two to 39 months of life on average.

The life expectancy of affected patients varies from few months to normal life expectancy, depending on phenotype. In general, SMA affects all muscles however usually progressive muscular weakness begins in proximal muscles like the hip, thigh and shoulder. The clinical manifestation of SMA varies from reduced fetal movements before birth to severe muscular weakness, delayed or missing motor skills, feeding difficulties, breathing problems with risk of aspiration and recurrent infections of the lungs ( Kindernetzwerk e.V.). Approximately one third of affected persons suffer from milder forms like SMA type II and type III (Dubowitz and Kugelberg-Welander disease, respectively). Characteristically, clinical manifestation of this type begins during the first months of life und is associated with severe disease course and death in early childhood. Most affected infants (approximately 70%) suffer from SMA type I (Werdnig-Hofmann disease) ( Muralidharan et al).

Type II (chronic infantile or intermediate form).

The different SMA types are divided into the following categories ( Early onset SMA: The clinical spectrum of SMA is categorized by the severity of symptoms and the age of clinical manifestation. The phenotype of 5q-SMA is modified by a second gene, the survival motor neuron 2 gene, The SMN2 gene is not able to produce functional SMN protein in adequate quantity however the number of SMN2 copies as well as the sequence of those copies influences the phenotypeВ ( Prior TW).

Sma type 3