Recently, Vaz et al. reported four families with complex hereditary spastic paraplegia (cHSP) and biallelic variants in PCYT2 encoding CTP: phosphoethanolamine cytidylyltransferase (ET), the rate-limiting enzyme for phosphatidylethanolamine biosynthesis. Patient-derived fibroblasts and plasma had significant abnormalities in both neutral etherlipid and etherphospholipid metabolism (Vaz et al., 2019). We wish to broaden the phenotypic and genetic spectrum of PCYT2-related disorders with two additional patients. Clinical features are detailed in Table 1. Case 1, a 46-year-old male, was born after a normal pregnancy from healthy first cousin consanguineous Spanish parents. He had an older sister who died at the age of 2 years due to a severe progressive muscle weakness of unknown aetiology. His development was considered as normal during childhood, until 12 years of age when he began to experience frequent falls and difficulties in running and climbing. Over the years, he reported weakness and lower limb stiffness. At age 49, neurological examination showed increased tone with proximal symmetrical weakness (MRC

4/5) of the lower limbs. Force and tone were normal in upper limbs. Deep tendon reflexes were globally brisk in all four limbs, with clonus and bilateral extensor plantar responses. He had hypopallesthesia of ankles with no other sensory deficits. No clinical signs of cerebellar involvement were present. He complained of urinary urge incontinence, was treated with baclofen, but improvement in leg spasticity was not clear and urinary urge worsened. Brain MRI at age 46 was strictly normal. EMG and nerve conduction studies were largely normal. Currently he is aged 59 years and walks with ankle-foot orthosis braces and needs a walking aid (cane) for longer distances. He finished primary school without difficulties, and obtained a job as a driver. Hitherto, there is no evidence of cognitive impairment. Case 2 is a 7-years-old male born to healthy, non-consanguineous African American parents. He has two healthy younger sisters. The patient’s mother had a positive group B strep test and she was treated with antibiotics prior to delivery. She reported occasional cannabis consumption during pregnancy. The patient was born at 38 weeks and 2 days