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Background  Without neonatal initiation of treatment, 80–90% of patients with glutaric aciduria type 1 (GA1) develop striatal injury during the first six years of life resulting in a complex, predominantly dystonic movement disorder. Onset of motor symptoms may be  acute  following encephalopathic crisis or  insidious  without apparent crisis. Additionally, so-called  late-onset  GA1 has been described in single patients diagnosed after the age of 6 years. With the aim of better characterizing and understanding  late-onset  GA1 we analyzed clinical findings, biochemical phenotype, and MRI changes of eight  late-onset  patients and compared these to eight control patients over the age of 6 years with early diagnosis and start of treatment.    Results  No  late-onset  or control patient had either dystonia or striatal lesions on MRI. All  late-onset  (8/8) patients were high excretors, but only four of eight control patients. Two of eight  late-onset  patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. Frontotemporal hypoplasia and white matter changes were present in all eight and subependymal lesions in six  late-onset  patients. At comparable age a greater proportion of  late-onset  patients had (non-specific) clinical symptoms and possibly subependymal nodules compared to control patients, in particular in comparison to the four clinically and MR-wise asymptomatic low-excreting control patients.    Conclusions  While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of  late-onset  GA1 and should trigger diagnostic investigation for this rare disease. Apart from their apparent non-susceptibility for striatal injury despite lack of treatment, patients with  late-on s et  GA1 are not categorically different from early treated control patients. Differences between  late-onset  patients and early treated control patients most likely reflect greater cumulative neurotoxicity in individuals remaining undiagnosed and untreated for years, even decades as well as the higher long-term risk of high excretors for intracerebral accumulation of neurotoxic metabolites compared to low excretors.    Electronic supplementary material  The online version of this article (doi:10.1186/s13023-017-0612-6) contains supplementary material, which is available to authorized users.

Extrastriatal changes in patients with late-onset glutaric aciduria type I highlight the risk of long-term neurotoxicity