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Sensorineural Hearing Loss in a Child with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) Treated with Cochlear Implantation

Biochemical/Metabolic and Therapeutics
  • Primary Categories:
    • Metabolic Genetics
  • Secondary Categories:
    • Metabolic Genetics
Introduction
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive mitochondrial DNA maintenance disorder caused by biallelic variants in the TYMP gene. MNGIE is a progressive and multisystemic disease characterized primarily by severe gastrointestinal dysmotility, cachexia, and neurological manifestations such as peripheral neuropathy, chronic progressive external ophthalmoplegia, and leukoencephalopathy.

Disease onset in MNGIE typically occurs in the second decade of life, often with gastrointestinal complaints. Progressive sensorineural hearing loss is increasingly recognized as a neurological feature in MNGIE, commonly presenting in the third to fourth decade. Hearing impairment is rarely present at the time of initial presentation in MNGIE patients and has not been previously reported in a child with MNGIE.

We report here a child presenting with rapidly progressive profound sensorineural hearing loss due to MNGIE who successfully underwent cochlear implantation.

Case Presentation
A 7-year-old Syrian female was referred due to hearing loss and abnormal MRI brain. Developmentally typical until 3.5 years old, she then developed progressive hearing loss after a self-limited febrile upper respiratory infection. Within two weeks, she lost receptive language comprehension. Otoacoustic emissions and auditory brainstem response at age 4 were consistent with profound bilateral sensorineural hearing loss.

After immigrating to the US at age 6, she was evaluated by otolaryngology and cochlear implantation was recommended. Pre-surgical brain MRI discovered asymmetric, confluent, bilateral areas of T2/FLAIR hyperintensities involving the periventricular white matter, centrum semiovale and corona radiata of the frontal, parietal and occipital lobes with sparing of the U-fibers.

Pedigree analysis revealed consanguinity as well as 14-year-old and 11-year-old brothers with short stature and poor weight gain. The younger of whom was also being evaluated for small bowel obstruction.

Physical examination revealed a thin-appearing non-dysmorphic female with weight-to-height ratio 3.3 standard deviations below the mean, and without ophthalmoparesis or ptosis. The remainder of her examination was unremarkable.

 

Diagnostic Workup
Comprehensive biochemical testing was normal. A multi-gene leukoencephalopathy panel identified homozygous pathogenic variants in TYMP (c.83_90dup [p.Pro31Thrfs*12]). Pathogenicity was confirmed with thymidine phosphorylase activity less than 1% of expected and markedly elevated serum thymidine and deoxyuridine.

Treatment and Management
Bilateral cochlear implantation was completed successfully without complication. Surveillance was recommended per the MNGIE International Network, including referrals to cardiology, ophthalmology, neurology and gastroenterology. Hematopoietic stem cell transplantation was discussed with the family, but ultimately not pursued.

Outcome and Follow-Up
Two years after activation, audiologic evaluation indicates hearing detection in the appropriate range bilaterally. She continues to make progress in intensive speech therapy and is enrolled in a hard-of-hearing school. Testing of at-risk family members indicates that her 14-year-old and 11-year-old brothers are both affected with MNGIE; each homozygous for the familial variant in TYMP.

Discussion
Our case highlights a rare presentation of MNGIE, with profound sensorineural hearing loss as an initial symptom in a young child. Hearing loss occurs in 39-45% of MNGIE patients, is generally progressive, adult in onset and often as part of a broader neurological decline. When present, hearing loss is seldom an early symptom or severe enough to necessitate cochlear implantation.

Successful cochlear implantation in this patient aligns with previous studies suggesting benefits in patients with mitochondrial disorders, though progression of retrocochlear degeneration remains a significant long-term concern. Significant improvements in speech perception and quality of life were previously reported in at least two adult MNGIE patients after cochlear implantation despite the presence of progressive polyneuropathy. Our case further supports the utility of cochlear implants for early auditory rehabilitation in MNGIE while underscoring the importance of genetic evaluation for at-risk relatives.

Conclusion
Consider MNGIE in patients with postlingual sensorineural hearing loss and systemic symptoms. Cochlear implantation remains a viable option for MNGIE-associated hearing loss, though longitudinal studies are necessary to evaluate long-term benefits.

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