Spastic paraplegia with crystalline retinopathy: A recognisable phenotype?

Abstract

Objective: Genetic diagnosis of hereditary spastic paraparesis (HSP) is often challenging because of lack of typical clinical or biochemical abnormalities. Case: An eight year old girl presented at the consultation with severe spastic paraparesis which had developed slowly over the last two years. More recently, a tremor in the hand became apparent. Perinatal history was unremarkable and early milestones were reached within normal limits. Cognitive functioning was normal. Dysmorphic features and skin lesions were not seen. Cerebral MRI and MRI of the spine were normal. Work-up was done for hereditary spastic paraparesis. Results: Fundoscopy showed a crystalline retinopathy as is typically seen in Sjögren-Larsson syndrome. As ichtyosis was absent in this patient we performed MRI spectroscopy, which did not reveal the abnormal lipid peak as seen in Sjögren-Larsson syndrome. Whole exome sequencing was performed and pathogenic mutations were not detected in ALDH3A2 nor in any other gene related to HSP. However, mutations where detected in an other gene related to aldehyde metabolism. Conclusion: Spastic paraplegia and crystalline retinopathy might be a new recognisable phenotype of HSP. We are looking for additional subjects to validate candidate genes.