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.

The biochemical subtype is a predictor for cognitive function in glutaric aciduria type 1: a national prospective follow-up study

“…Anthropometric and MRI studies elucidated phenotypic differences between the two biochemical phenotypes; HE individuals more often than LE individuals developed macrocephaly and progressive white matter abnormalities with unclear clinical relevance 24,25 . Recently, chronic kidney dysfunction, which was not impacted by recommended therapy or the neurologic phenotype, was identified as a first non-neurologic disease manifestation 1,4 , and malignant brain tumours and audiological manifestations were described in single patients 26,27 . It had been hypothesized that the clinical phenotype of GA1 individuals does not typically include cognitive impairment regardless of severe dystonic MD 14 .…”

Sensorineural Hearing Loss in a Child with Succinic Semialdehyde Dehydrogenase Deficiency

“… 25 However, the prevalence of sensorineural hearing loss was found to be significantly higher in patients with glutaric aciduria type 1 treated in intensive care units for metabolic crises. 26 One of the hallmarks of glutaric aciduria type 1 is the presence of abnormally high signal in globi pallidi detected by MRI. 27 Moreover, decreased functional connectivity in ipsilateral globus pallidus was found in patients with unilateral hearing loss by the use of resting state functional connectivity MRI.…”

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

“…Hearing function : A recent Taiwanese study with 13 patients, with methodical limitations, however, reported on mild hearing impairment, particularly in patients after intensive care treatment 212 . It is unknown whether early or late‐treated individuals with GA1 are generally at increased risk for developing hearing impairment.…”