Abstract:
Glutaric aciduria is an autosomal recessively inherited metabolic disorder caused by deficiency of the enzyme glutaryl-coenzyme-A-dehydrogenase. It is characterized by encephalopathic crises resulting in striatal lesions and severe dystonic movement disorder. Its early diagnosis, by neonatal screening, is usually based on increased glutarylcarnitine in blood and glutaric acid and 3-hydroxyglutaric acid in urine. We present a retrospective review of the patients diagnosed in our center in the last 25 years to evaluate comparatively the medium-long term clinical evolution of those diagnosed by newborn screening (NBS) versus those diagnosed clinically. Of 11 patients (6 males and 5 females), 9 were diagnosed by NBS and 2 (cases 1 and 2) by clinical diagnosis. Case 1, debuted with clinical encephalitis at 11 years of age, causing severe dystonic spastic tetraparesis, and died at 34 years of age due to acute respiratory failure. The second case is a false negative of NBS due to low excretion of glutaric acid in urine with normal glutarylcarnitine levels in blood. He was identified by elevation of glutarylcarnitine in urine after clinical onsetat 14 months with encephalopathy during viral infectious. His subsequent neurological development was favorable except for slight muscle spasticity. Of the NBS group, 100% have normal neurocognitive development (IQ performed in 6/9 patients: normal), 22% presentattention deficit hyperactivity disorder (ADHD) and one patient has tics. Only 18% of the series presented macrocephaly, although 66% of NBS patients maintained evolutionary head circumference >80% and 27% presented enlargement of the subarachnoid spaces. Other manifestations were language disorders in three patients. None of NBS patients presented encephalopathic crises after diagnosis. All of them received treatment with carnitine and a diet restrictive in lysine and tryptophan, with slight dietary liberalization from the first decade of life. Thirteen different variants were identified in the GCDH gene, two (R88H and L103F) not previously described, being R227P the most frequent variant (18% of alleles).
Audience Takeway
- The medium-long term follow-up of our series corroborates the importance of neonatal screening to improve the prognosis of this entity, allowing a good quality of life, without remarkable neurodevelopmental alterations in adherent patients.
- To highlight the evidence of hyperactivity/attention deficit disorder and language disorders in 27% of the patients.
- To highlight the role of urine glutarylcarnitine as a screening marker in false negative cases.
