Exome sequencing reveals two FA2H mutations in a non-consanguineous Italian family

Hereditary spastic paraplegia (HSP, MIM 18260) comprises a group of inherited neurodegenerative disorders that are characterized by progressive spasticity and weakness of lower extremities, due to a length dependent dying back degeneration of corticospinal tracts. Clinically, HSP can be classified as pure if spastic paraparesis occurs in isolation, and complex if other neurological or non-neurological features are present. Autosomal dominant (AD), autosomal recessive (AR) and X linked modes of inheritance have been described).Among these, the autosomal recessive spastic paraplegia form 35 (SPG35) is characterized by childhood onset of spasticity, cognitive decline and leukodystrophy). Additional clinical features such as seizures, dysphagia, dysarthria, dystonia, neuropathy and brain iron accumulation were also observed (2-3). Several patients were described with different combination of these features. Mutations in the fatty acid 2-hydroxylase (FA2H) gene have been associated to the SPG35 form. FA2H encodes a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent monooxygenase, involved in the synthesis of 2-hydroxy fatty acid galactolipids, that are the major component of myelin sheath).