Spastic Paraplegia 64, Autosomal Recessive

A number sign (#) is used with this entry because autosomal recessive spastic paraplegia-64 (SPG64) is caused by homozygous mutation in the ENTPD1 gene (601752) on chromosome 10q24.

For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).

Clinical Features

Novarino et al. (2014) performed whole-exome sequencing network analysis to identify mutations in consanguineous families with hereditary spastic paraplegia. In 1 family with a complicated form of spastic paraplegia (family 1242), 2 brothers presented between 3 and 4 years of age with abnormal gait. When last examined, one brother, aged 12, was nonambulatory, and the other, aged 6, could walk with support. Both brothers had deep tendon reflexes, dysarthria, and spasticity. Neither had had an MRI, but both had borderline IQ, aggressiveness, delayed puberty, and microcephaly. In another family with a complicated form of spastic paraplegia (family 1800), a brother and sister presented at age 1 year with unsteady gait. When last examined, one at age 11 years and the other at age 21 years, they could still walk without support. Both sibs had dysarthria and spasticity; 1 had absent reflexes, and the other had normal reflexes. Both had mild white matter changes on brain MRI and moderate intellectual disability.

Molecular Genetics

In affected members of 2 consanguineous families segregating autosomal recessive spastic paraplegia, Novarino et al. (2014) identified homozygosity for a missense mutation (G217R; 601752.0001) and a nonsense mutation (E181X; 601752.0002).