RESUMO

Background and Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive progressive neurodegenerative primary motor neuron disorder caused by biallelic variants of the survival motor neuron 1 (SMN1) gene. The most recent SMA best practice recommendations were published in 2018 shortly after the approval of the first SMN-enhancing treatment. The availability of disease-modifying therapies for 5q SMA and implementation of SMA newborn screening (NBS) has led to urgency to update the SMA best practice recommendations for diagnosis and to reevaluate the current classification of SMA. In addition, the availability of disease-modifying therapies has opened the door to explore improved diagnosis of adult-onset SMA. Methods: A systematic literature review was conducted on SMA NBS. An SMA working group of American and European health care providers developed recommendations through a modified Delphi technique with serial surveys and virtual meeting feedback on SMA diagnosis to fill information gaps for topics with limited evidence. A community working group of an individual with SMA and caregivers provided insight and perspective on SMA diagnosis and support through a virtual meeting to guide recommendations. Results: The health care provider working group achieved consensus that SMA NBS is essential to include in the updated best practice for SMA diagnosis (100%). Recommendations for the following are described: characterizing NBS-identified infants before treatment; minimum recommendations for starting or offering SMA NBS in a state or country; recommendations for activities and services to be provided by an SMA specialty care center accepting SMA NBS referrals; and recommendations for partnership with individuals with SMA and caregivers to support NBS-identified infants and their caregivers. Limited data are available to advance efficient diagnosis of adult-onset SMA. Discussion: Updating best practice recommendations for SMA diagnosis to include SMA NBS implementation is essential to advancing care for individuals with SMA. In addition to testing, processes for the efficient management of positive newborn screen with access to knowledgeable and skilled health care providers and access to treatment options is critical to successful early diagnosis. Additional evidence is required to improve adult-onset SMA diagnosis.

RESUMO

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity.

Assuntos

RESUMO

Bcl-2-associated athanogene 3 (BAG3) myopathy is a rare myofibrillar myopathy characterized by toe walking and clumsiness in the first decade with rapid progression to cardiomyopathy and restrictive lung disease in the second decade. Most patients (18 patients) have the c.626C >T (p.Pro209Leu) mutation. We describe BAG3 myopathy due to p.Pro209Leu in a 13-year-old girl with initial prominent neuropathic phenotype and no cardiac or respiratory involvement. Parents reported toe walking and clumsiness since 3 years old. Examination at the age of 13 years showed findings suggestive of Charcot-Marie-Tooth disease. Nerve conduction studies revealed demyelinating polyneuropathy. Next-generation sequencing panel for inherited neuropathies was unrevealing. Whole exome sequencing identified a de novo mutation in BAG3. Muscle biopsy confirmed myofibrillar myopathy. No cardiac involvement or symptoms of respiratory involvement at the age of 14 years. This case emphasizes the phenotypic variability of BAG3 myopathy and the importance of thorough electrophysiological examination and muscle pathology for establishing a precise diagnosis.

Assuntos