Analysis of clinical features and the results of mass spectrometry with glutaric acidemia type I

Objective For clinically understanding of glutaric acidemia type Ⅰ (GA-Ⅰ), the relationship of the clinical manifestations and the serum levels of free carnitine (C0), glutarylcarnitine (C5DC), and capryloylcarnitine (C8) as well as the urinary levels of glutaric acid and mevalonolactone of patients with GA-Ⅰ were studied. Methods From December 2007 to April 2016, a total of 62 patients with GA-Ⅰ (GA-Ⅰ group) and 62 healthy children (control group) were included. Tandem mass spectrometry was used to measure the blood levels of C0, C5DC, and C8, while, gas chromatography-mass spectrometry was used to measure the urine levels of glutaric acid and mevalonolactone. Results Total 62 cases, 36 males and 26 females, median age 1.2 years (range from 27 days to 9.3 years) were enrolled. Clinical features included macrocephaly, dyskinesia, seizures, growth and mental retardation, abnormal muscular tension, as well as feeding difficulties. The median levels of C5DC, C5DC/C8, glutaric acid, mevalonolactone were 0.90 μmol/L, 24.25, 936.30 mmol/mol creatinine, and 141.5 mmol/mol creatinine respectively, which were higher than those of the control group (all P<0.01). While the median level of C0 was between the reference value, and the median level of C8 was lower than the control group (0.04 vs 0.10 μmol/L). Cranial magnetic resonance image (MRI) had been carried out in 34 patients. Multiple and symmetrical abnormal signal in white matter and basal ganglia, widening of the sylvian fissure, expansion of cerebro-spinal fluid spaces anterior to the temporal lobes were cardinal signs of GA-Ⅰ. Conclusions Patients with GA-Ⅰ present with complex and variable clinical features, mainly including abnormal increase of head circumference, retarded motor and language development, repeated convulsions and characteristic abnormalities in brain MRI. Significant increase in the blood levels of C5DC and C5DC/C8 and in urine level of glutaricacid and mevalonolactonemay are specific to the diagnosis of GA-Ⅰ. For mild cases, repeated tests and genomic mutation analysis are necessary. (Chin J Endocrinol Metab, 2017, 33: 730-734) Key words: Glutaric acidemia Ⅰ; Glutarylcarnitine; Glutaric acid; Tandem mass spectrometry; Gas chromatography-mass spectrometry