Pediatric Neurology Group

The field of nervous system diseases has undergone a major revolution during the recent decades. As a result, many genetic defects are known to be responsible for neurological diseases, but frequently not much is known about the resulting protein products and the pathophysiological basis behind the disease. Both Prof. Hinttala and Prof. Uusimaa have a solid background in characterizing novel disease genes causing neurological and multiorgan disorders from the well-defined patient cohorts of Northern Finland. They have identified and characterized several novel inherited diseases: a hyperkinetic movement disorder caused by pathogenic variants in the striatum-enriched phosphodiesterase 10A (PDE10A) (OMIM 616921) (Diggle et al., 2016), FINCA (fibrosis, infection susceptibility/immunodeficiency/intellectual disability, neurodevelopmental disorder/neurodegeneration and chronic anemia/cerebral angiomatosis) disease caused by variants in NHLRC2 (OMIM 618278) (Paakkola et al., 2018; Uusimaa et al., 2018), HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) caused by variants in PH4TM (OMIM 618493) (Rahikkala et al., 2019), and SCBMS syndrome (seizures, cortical blindness, and microcephaly syndrome) with immunodeficiency and mitochondrial dysfunction caused by variants in the DIAPH1 (OMIM 616632) (Kaustio et al., 2021). In addition, Prof. Uusimaa and her colleagues have recently demonstrated a characteristics urine metabolite pattern as a biomarker for cytosolic phosphoenoylpyruvate carboxykinase (PEPCK) deficiency with a novel Finnish variant (Vieira et al., 2017), and by using this novel biomarker they have identified 23 additional Finnish patients with PEPCK deficiency as a cause of a treatable metabolic disease (Vieira et al., 2021). Since the significantly higher frequency of the novel variant in Finnish population (1:100), PEPCK deficiency is the most recent addition to the Finnish Disease Heritage (Uusimaa et al., 2022).