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Título

A NOVEL SPLICE-SITE SGCB MUTATION CAUSING LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2E IN A BRAZILIAN PATIENT

Apresentação do caso

An 8-year-old girl, born from consanguineous parents, was admitted with a history of difficulty getting up from the floor since the second year of life. Thereafter, she developed muscle pain, exercise intolerance (particularly walking long distances) and evident hyperlordosis. On neurological examination, there was flaccid proximal-predominant tetraparesis. There was no evidence of sensory or cardiac involvement. During the investigation, aldolase, creatine phosphokinase (CPK), lactate dehydrogenase (DHL), and alanine aminotransferase (ALT) were found to be remarkably elevated ( up to 5x the upper limit of normal). Genetic testing revealed the likely pathogenic splice-site c.753+5G>A SGCB variant in homozygosis, which confirmed the hypothesis of limb-girdle muscular dystrophy (LGMD 2E).

Discussão

DISCUSSION: The SGCB gene encodes the beta subunit of the sarcoglycan protein complex, which is important for maintenance of sarcolemmal integrity. The sarcoglycanopathies are caused by pathogenic variants in any of the genes related to the sarcoglycan complex. They are considered the most severe forms of autosomal recessive LGMDs (LGMD 2). Genetic epidemiology studies reveal that the most frequent form worldwide is LGMD 2D, followed by LGMD 2C, and then LGMD 2E and LGMD 2F. Approximately 50 mutations in the SCGB gene have been identified in people with LGM 2E, which is characterized by muscle weakness and wasting, particularly in the shoulders, hips, and limbs. Dilated cardiomyopathy is a conspicuous finding later in disease course. Severe clinical DMD - like presentations tend to be more common among sarcoglycanopathies patients, with onset early in childhood and confinement to a wheelchair before the age of sixteen; nevertheless, milder courses (including pseudometabolic phenotypes) have also been described in LGMD 2C, LGMD 2D, and LGMD 2E patients as well as intrafamilial variability.

Comentários finais

CONCLUSION: This case describes a milder manifestation of LGMD 2E, a sarcoglycanopathy caused by biallelic SGCB loss-of-function variants. It has been associated with muscle weakness of pelvic and scapular girdle as well as cardiomyopathy. Proper recognition of this rare LGMD subtype in children enables adequate management and genetic counseling.

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Área

Neurogenética