Audiological and otologic manifestations of glutaric aciduria type I

Abstract

Background: Glutaric aciduria type 1 (GA-1) is a rare disease connected with speech delay and neurological deficits. However, the audiological and otologic profiles of GA-1 have not yet been fully characterized. To our knowledge, this is the largest study of comprehensive audiological and otologic evaluation in patients with GA-1 to date.

Methods: Thirteen patients diagnosed with GA-1 between January 1994 and December 2019 with audiological, radiological and genetic manifestations were retrospectively analyzed. Hearing tests were performed in all patients. MRI was performed for radiological evaluation.

Results: Hearing loss was found in 76.9% (10/13) of GA-1 patients, including slight hearing loss in 46.1% (6/13) of patients, mild hearing loss in 15.4% (2/13) of patients, and moderate hearing loss in 7.7% (1/13) of patients. Normal hearing thresholds were seen in 23% (3/13) of patients. Patients with intensive care unit (ICU) admission history showed significantly worse hearing than those without (29.17 ± 12.47 vs 13.56 ± 3.93 dB HL, 95% CI 2.92-24.70, p = 0.0176). One patient had moderate sensorineural hearing loss and a past history of acute encephalopathic crisis. No usual causative gene mutations associated with hearing loss were found in these patients. MRI showed a normal vestibulocochlear apparatus and cochlear nerve. One patient with extensive injury of the basal ganglia on MRI after acute encephalopathic crisis was found to have moderate sensorineural hearing loss. Two patients with disability scores above 5 were found to have mild to moderate hearing impairment. No obvious correlation between macrocephaly and hearing loss was found.

Conclusion: A high prevalence of hearing impairment is found in GA-1 patients. Adequate audiological evaluation is essential for these patients, especially for those after encephalopathic crises or with ICU admission history.

Keywords: Glutaric aciduria type 1; Hereditary hearing loss; Syndromic hearing loss.

Fig. 1

Mean hearing thresholds in patients with and without an ICU admission history. Patients with a history of ICU admission showed worse hearing performance than those without (mean ± SD = 29.17 ± 12.47 vs 13.56 ± 3.93 dB HL, 95% confidence interval (CI) − 0.04558 to 28.05, p = 0.0176, *p < 0.05)

Fig. 2

MR images of patients with GA-1. A-C. The pattern of putamen injury in case 6 with a history of seizure and acute encephalopathic crisis is shown. (A) T2 weighted (T2W) MRI. The red arrow indicates extensively hyperintense striatal involvement in T2W MRI. (B) Diffusion weighted images. The red arrow reveals injury with clearly elevated diffusion of the dorsolateral putamen on diffusion weighted images. (C) Apparent diffusion coefficient map. The image shows minimal restricted diffusion affecting the bilateral putamen. (D) Illustration of imaging of the central auditory pathway. An oblique coronal section onT2WI MRI of case 3 shows the hypointense white matter tract. Letters (a) to (e) denote the apparatus of the auditory pathway. (a) Auditory cortex, (b) Thalamus (medial geniculate body), (c) Midbrain (inferior colliculus), (d) Pons (superior olivary nucleus), (e) Cochlea. Note that no space occupying lesion was noted along the tracts