L-2-hidroksiglutarik asidüri hastalarında klinik, nöroradyolojik ve genetik bulguların değerlendirilmesi

Abstract

Aim: L-2-hydroxyglutaric aciduria is a slowly progressive neurometabolic disorder caused by an enzymatic deficiency of L-2-hydroxyglutarate dehydrogenase. Here, we aimed to evaluate the clinical, neuroradiologic, and genotypic characteristics of patients with L-2-hydroxyglutaric aciduria who were followed in our outpatient clinic. Material and Methods: Twenty-five patients with L-2-hydroxyglutaric aciduria were enrolled in the study. Data regarding demographic, clinical, and neuroradiologic findings and molecular analysis were evaluated retrospectively. Results: The mean age of patients at the time of diagnosis was 12.09±8.02 years, whereas the mean age at the time of the first symptoms was 39.47±29.96 months. Diagnostic delay was found as 9.95±7.78 years. Developmental delay, decrease in school success, and seizures were the most common initial symptoms; however, behavioral problems and seizures became more prominent in the disease course. At the time of diagnosis, mental retardation and at least one pathologic cerebellar finding were detected in all symptomatic patients. Three patients developed brain tumors. The most common neuroimaging findings were subcortical white matter changes and cerebellar dentate nucleus involvement. In one patient, there was only isolated basal ganglia involvement without white matter lesions. Patients with similar genotypic features exhibited different clinical and radiologic findings. Conclusion: Although clinical symptoms appear early in L-2-hydroxyglutaric aciduria, there is approximately a ten-year delay in diagnosis. In subjects in whom brain tumor is detected in early childhood, L-2-hydroxyglutaric aciduria should be considered in the differential diagnosis in the presence of mental retardation accompanied by developmental delay, cerebellar and pyramidal findings, and behavior disorders in a wide spectrum ranging from autism spectrum disorder to psychosis. In patients with L-2-hydroxyglutaric aciduria, incipient headache, tinnitus, altered consciousness, and seizures can be indicative of brain tumors.

From Shadows to Diagnosis: Unraveling L-2 Hydroxyglutaric Aciduria in Adulthood

“…Several publications have reported delayed diagnosis in adult patients in their late 40s and 50s. 3 Cases diagnosed in the third and fourth decades of their lives were also reported in the studies of Zübarioğlu et al 12 from Turkey.…”

Glutaric aciduria and L-2-hydroxyglutaric aciduria: Clinical and molecular findings of 35 patients from Turkey

“…Crises are usually triggered by febrile illness and catabolic stress [ 1 , 3 ]. In the literature, the mean age at first symptom varies between 1 and 6 months, and the mean age at first diagnosis varies between 4 and 14 months [ 1 , 3 , [7] , [8] , [9] , [10] , [11] ]. In our cohort, while the age of first AEC was consistent with the literature, the mean age at first symptoms was older.…”

“…The most common variants in L2HGDH gene were c.164G > A (p.Gly55Asp) and c.1115delT (p.Met372fs). The c.164G > A mutation in the L2HGDH gene was previously reported only in Turkish patients [ 9 , 10 ]. The novel variant of the L2HGDH gene was the c.738 + 5A > G splice variant.…”