Dados do Trabalho

Título

CAPN1 mutation associated with spastic paraplegia, a rare progressive gait disorder with few reports in literature.

RESUMO

CAS PRESENTATION: Two young patients attended our clinic presenting difficulties to walk at the same age, 30 years old, with progressive worsening. A woman, with a history of two ischemic strokes, the first at 24, and later with 40 years of age, struggles to walk at 30 years of age, associated with weakness in the lower limbs, hypertonia, signs of pyramidal release and ataxia. Neuroimaging showed only an area of previous ischemic stroke at the right frontoparietoinsular region. She had no similar family history or consanguinity but is of German descent. She improved symptons with thiozidine. The second case, a man, started the symptoms with difficulty in walking, progressivly worsening, associated with dysarthria, global spasticity, ataxia, significant postural instability and club foot. Neuroimaging showed atrophy of the brainstem and cerebellum. He had No pathological antecedents and had Portuguese ancestry. The man has family members with confirmed disease, a sister who started symptoms at 20 years old (homozygous) and another asymptomatic sister (heterozygous). Both cases were diagnosed after genetic testing, confirming the CAPN1 mutation.
DISCUSSION: CAPN1 is a gene involved in protein coding and related to nervous system development and the integrin pathway, also associated with autophagy-lysossomal pathway in cerebral ischemia scenario. Structural alterations in this gene are associated with Autosomal Recessive Spastic Paraplegia 76, spasticity and possibly with neuronal damage secondary to impairment in autophagic flux during an cerebral ischemia. Autosomal recessive spastic paraplegia spastic type 76 usually begins in adulthood with slow progression, leading to spasticity and hyperreflexia, as well as dysarthria. Other findings that may be found are foot deformities (clubfoot), plantar extension reflex and ataxia.
FINAL COMMENTS: the finding of gait disturbances with progressive worsening in youth or early adulthood should raise as a suspicion, among other etiologies, of genetic diseases. Often seen as sporadic forms of spastic paraplegia, only with genetic testing is a correct diagnosis possible.

Palavras Chave

CAPN1, spastic paraplegia, ataxia, cerebral ischemia