Highlights
- •Inherited metabolic disorders (IMDs) are often associated with hearing loss (HL).
- •We systematically reviewed associations between IMDs and HL.
- •Incidence, etiology, pathophysiology, and treatment were discussed.
- •Better understanding of these associations may improve diagnosis and treatment.
Abstract
Inherited metabolic disorders (IMDs) have been observed in individuals with hearing
loss (HL), but IMDs are rarely the cause of syndromic HL. With early diagnosis, management
of HL is more effective and cortical reorganization is possible with hearing aids
or cochlear implants. This review describes relationships between IMDs and HL in terms
of incidence, etiology of HL, pathophysiology, and treatment. Forty types of IMDs
are described in the literature, mainly in case reports. Management and prognosis
are noted where existing. We also describe IMDs with HL given age of occurrence of
HL. Reviewing the main IMDs that are associated with HL may provide an additional
clinical tool with which to better diagnose syndromic HL.
Abbreviations:
AR (autosomal recessive), CDG (congenital disorder of glycosylation), CI (cochlear implant), DBP (D-bifunctional protein deficiency), ERT (enzyme replacement therapy), GAG (glycosaminoglycan), HL (hearing loss), IEM (inborn error of metabolism), IRD (infantile Refsum disease), MGA (methylglutaconic aciduria), MPS (mucopolysaccharidosis), MRI (magnetic resonance imaging), NALD (neonatal adrenoleukodystrophy), P-NALD (pseudoneonatal adrenoleukodystrophy), ROS (reactive oxygen species), SNHL (sensorineural hearing loss), SOS (spondylo ocular syndrome), X-ALD (X-linked adrenoleukodystrophy), ZS (Zellweger syndrome), ZSD (Zellweger spectrum disorder)Keywords
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References
- Sensorineural hearing loss in children.Lancet. 2005 Mar 5; 365: 879-890
- Inborn errors of metabolism.Adv Clin Chem. 2016; 73: 195-250
- Inborn errors of metabolism overview: pathophysiology, manifestations, evaluation, and management.Pediatr Clin North Am. 2018; 65: 179-208
- Maladies héréditaires du métabolisme: signes anténatals et diagnostic biologique [prenatal symptoms and diagnosis of inherited metabolic diseases].Arch Pediatr. 2012 Sep; 19: 959-969
- Inborn errors of metabolism in the 21st century: past to present.Ann Transl Med. 2018 Dec; 6: 467
- Newborn screening: history, current status, and future directions.Pediatr Clin North Am. 2018; 65: 389-405
- Visual cross-modal re-organization in children with cochlear implants.PLoS One. 2016; 11e0147793
- Hearing loss is a common feature of symptomatic children with profound biotinidase deficiency.J Pediatr. 2002 Feb; 140: 242-246
- Localization of biotinidase in the brain: implications for its role in hearing loss in biotinidase deficiency.Hear Res. 2002 Nov; 173: 62-68
- Outcomes of oral biotin treatment in patients with biotinidase deficiency - twenty years follow-up.Mol Genet Metab Rep. 2015 Dec; 5: 33-35
- Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.Ann Neurol. 2017 Dec; 82: 1004-1015
- Increased reactive oxygen species (ROS) production and low catalase level in fibroblasts of a girl with MEGDEL association (Leigh syndrome, deafness, 3-methylglutaconic aciduria).Folia Neuropathol. 2011; 49: 56-63
- Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.Mol Genet Metab. 2006 May; 88: 47-52
- Congenital cataract, muscular hypotonia, developmental delay and sensorineural hearing loss associated with a defect in copper metabolism.J Inherit Metab Dis. 2005; 28: 479-492
- Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with congenital cataracts, hearing loss, and low serum copper and ceruloplasmin.Am J Hum Genet. 2012 Jan 13; 90: 61-68
- Huppke-Brendel syndrome in a seven months old boy with a novel 2-bp deletion in SLC33A1.Metab Brain Dis. 2016; 31: 1195-1198
- Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment.J Inherit Metab Dis. 2011 Feb; 34: 159-164
- The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives.Orphanet J Rare Dis. 2012 Oct 29; 7: 83
- Mutations in riboflavin transporter present with severe sensory loss and deafness in childhood.Muscle Nerve. 2014 Nov; 50: 775-779
- Neurotologic and functional MRI findings in a patient with bilateral profound deafness having Brown-Vialetto-Van Leare syndrome.Otol Neurotol. 2014 Oct; 35: 1495-1500
- Auditory neuropathy spectrum disorder with Brown-Vialetto-Van Laere syndrome: challenges in hearing rehabilitation.J Laryngol Otol. 2015 May; 129: 504-508
- Cochlear implantation in children with auditory neuropathy: lessons from Brown-Vialetto-Van Laere syndrome.Cochlear Implants Int. 2019; 20: 31-38
- Ichthyosiform dermatosis with systemic lipidosis.Arch Dermatol. 1974 Aug; 110: 261-266
- Neutral-lipid storage disease: a new disorder of lipid metabolism.Br Med J. 1975 Mar 8; 1: 553-555
- Ichthyosis and neutral lipid storage disease.Am J Med Genet. 1985 Apr; 20: 711-726
- Chanarin-Dorfman syndrome.Turk J Gastroenterol Off J Turk Soc Gastroenterol. 2019; 30: 105-108
- Neurological symptoms in Hypophosphatasia.Osteoporos Int. 2019 Feb; 30: 469-480
- An X-linked syndrome characterised by hyperuricaemia, deafness, and neurodevelopmental abnormalities.The Lancet. 1982 Jul; 320: 68-70
- An inborn error of purine metabolism, deafness and neurodevelopmental abnormality.Neuropediatrics. 1985 May; 16: 106-108
- Inherited superactivity of phosphoribosylpyrophosphate synthetase: association of uric acid overproduction and sensorineural deafness.Am J Med. 1988 Sep; 85: 383-390
- Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.Nat Genet. 1999 Jul; 22: 300-304
- Targeted disruption of Slc19a2, the gene encoding the high-affinity thiamin transporter Thtr-1, causes diabetes mellitus, sensorineural deafness and megaloblastosis in mice.Hum Mol Genet. 2002 Nov 1; 11: 2951-2960
- Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome.Am J Med Genet A. 2004 Mar 15; 125A: 299-305
- Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families.Acta Paediatr Oslo Nor 1992. 2006 Jan; 95: 99-104
- Hereditary myoclonus and progressive muscular atrophy: a new syndrome.Trans Am Neurol Assoc. 1978; 103: 116-118
- Acid ceramidase deficiency associated with spinal muscular atrophy with progressive myoclonic epilepsy.Neuromuscul Disord. 2015 Dec; 25: 959-963
- Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia.Orphanet J Rare Dis. 2017 13; 12: 30
- Mutations in ABHD12 cause the neurodegenerative disease PHARC: an inborn error of endocannabinoid metabolism.Am J Hum Genet. 2010 Sep 10; 87: 410-417
- Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC and assessment of their functional effects.Hum Mutat. 2013 Dec; 34: 1672-1678
- Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome.J Peripher Nerv Syst. 2020; 25: 112-116
- Prevalence of lysosomal storage disorders.JAMA. 1999 Jan 20; 281: 249-254
- Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease.Brain J Neurol. 2007 Jan; 130: 143-150
- Hearing loss in Fabry disease: the effect of agalsidase alfa replacement therapy.J Inherit Metab Dis. 2003; 26: 787-794
- Vestibular and auditory deficits in Fabry disease and their response to enzyme replacement therapy.J Neurol. 2007 Oct; 254: 1433-1442
- Ear symptoms in children with Fabry disease: data from the Fabry outcome survey.J Inherit Metab Dis. 2009 Dec; 32: 739
- Hearing loss in children with Fabry disease.J Inherit Metab Dis. 2017; 40: 725-731
- Otologic histopathology of Fabry’s disease.Ann Otol Rhinol Laryngol. 1989 May; 98: 359-363
- The changing landscape of Fabry disease.Clin J Am Soc Nephrol. 2020 07; 15: 569-576
- Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations.J Inherit Metab Dis. 2018; 41: 865-876
- Hearing loss is part of the clinical picture of ENPP1 loss of function mutation.Horm Res Paediatr. 2014; 81: 63-66
- Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.Nat Rev Nephrol. 2019; 15: 435-455
- Hypophosphatemic rickets.Pediatr Clin North Am. 2019 Feb 1; 66: 179-207
- Hearing loss and fluctuating hearing levels in X-linked hypophosphataemic osteomalacia.J Laryngol Otol. 2009 Jan; 123: 136-140
- Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options.Neurotherapeutics. 2013 Apr; 10: 186-198
- SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness.Brain J Neurol. 2007 Mar; 130: 862-874
- Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion.Mol Genet Metab. 2017; 120: 213-222
- Phenotypic heterogeneity in families with the myoclonic epilepsy and ragged-red fiber disease point mutation in mitochondrial DNA.Ann Neurol. 1993; 33: 640-645
- Expanded phenotypic spectrum of the m.8344A>G “MERRF” mutation: data from the German mitoNET registry.J Neurol. 2016 May; 263: 961-972
- Maternally inherited diabetes and deafness: a multicenter study.Ann Intern Med. 2001 May 1; 134: 721-728
- Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation.Diabet Med. 2008 Apr; 25: 383-399
- The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation.Diabetologia. 1998 May; 41: 584-588
- Melas: an original case and clinical criteria for diagnosis.Neuromuscul Disord. 1992; 2: 125-135
- MELAS: a nationwide prospective cohort study of 96 patients in Japan.Biochim Biophys Acta. 2012 May; 1820: 619-624
- Audiological and vestibular findings in subjects with MELAS syndrome.J Int Adv Otol. 2019 Aug; 15: 296-303
- Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review.Orphanet J Rare Dis. 2018 21; 13: 35
- Cochlear origin of hearing loss in MELAS syndrome.Ann Neurol. 1998 Mar; 43: 350-359
- Cochlear implantation in maternal inherited diabetes and deafness syndrome.J Laryngol Otol. 2002 May; 116: 373-375
- MELAS syndrome: clinical manifestations, pathogenesis, and treatment options.Mol Genet Metab. 2015 Oct; 116: 4-12
- Hearing loss is an early consequence of Npc1 gene deletion in the mouse model of Niemann-Pick disease, type C.J Assoc Res Otolaryngol. 2014 Aug; 15: 529-541
- Otorhinolaryngological, audiovestibular and swallowing manifestations of patients with Niemann-Pick disease Type C.Int J Pediatr Otorhinolaryngol. 2016 Jan; 80: 1-4
- Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study.Lancet Neurol. 2007 Sep; 6: 765-772
- Prevalence of hearing loss in patients with late-onset Pompe disease: audiological and otological consequences.Int J Audiol. 2013 Dec; 52: 816-823
- Hearing loss in infantile Pompe’s disease and determination of underlying pathology in the knockout mouse.Neurobiol Dis. 2004 Jun; 16: 14-20
- Hearing loss in Pompe disease revisited: results from a study of 24 children.J Inherit Metab Dis. 2010 Oct; 33: 597-602
- Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: report of seven new cases.Am J Med Genet A. 2019; 179: 1756-1763
- The natural course and complications of alpha-mannosidosis--a retrospective and descriptive study.J Inherit Metab Dis. 2014 Jan; 37: 79-82
- Hearing loss due to mannosidosis and otitis media with effusion. A case report and review of audiological assessments in children with otitis media with effusion.J Laryngol Otol. 2003 Apr; 117: 307-309
- Alpha-Mannosidosis: therapeutic strategies.Int J Mol Sci. 2018 May; 17: 19(5)
- Effective treatment of alpha-mannosidosis by allogeneic hematopoietic stem cell transplantation.J Pediatr. 2004 May; 144: 569-573
- β-Mannosidosis caused by a novel homozygous intragenic inverted duplication in MANBA.Cold Spring Harb Mol Case Stud. 2019; 5
- Atypical Gilles de la Tourette Syndrome with beta-mannosidase deficiency.Arch Neurol. 2006 Jan; 63: 129-131
- Clinical and biochemical spectrum of D-bifunctional protein deficiency.Ann Neurol. 2006 Jan; 59: 92-104
- Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency.Neurol Genet. 2016 Dec; 2e114
- The inflammatory response in acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy).Endocrinology. 2012 Jun; 153: 2568-2575
- Peroxisomal acyl CoA oxidase deficiency.J Pediatr. 2002 Jan; 140: 128-130
- Straight-chain acyl-CoA oxidase deficiency presenting with dysmorphia, neurodevelopmental autistic-type regression and a selective pattern of leukodystrophy.J Inherit Metab Dis. 2004; 27: 105-108
- Adrenoleukodystrophy and Zellweger syndrome.Prog Clin Biol Res. 1990; 321: 511-535
- Peroxisome biogenesis disorders.Biochim Biophys Acta. 2006 Dec; 1763: 1733-1748
- Clinical approach to inherited peroxisomal disorders: a series of 27 patients.Ann Neurol. 1998 Nov; 44: 720-730
- Peroxisome biogenesis disorders with prolonged survival: phenotypic expression in a cohort of 31 patients.Am J Med Genet A. 2004 May 1; 126A: 333-338
- Audiological findings in Infantile Refsum disease.Int J Pediatr Otorhinolaryngol. 2015 Aug; 79: 1366-1369
- A newly identified mutation in the PEX26 gene is associated with a milder form of Zellweger spectrum disorder.Cold Spring Harb Mol Case Stud. 2019 Feb 1; 5: a003483
- Peroxisome biogenesis disorders in the Zellweger spectrum: an overview of current diagnosis, clinical manifestations, and treatment guidelines.Mol Genet Metab. 2016 Mar; 117: 313-321
- CDG nomenclature: time for a change!.Biochim Biophys Acta. 2009 Sep; 1792: 825-826
- RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation.J Inherit Metab Dis. 2009 Dec; 32: S335-S338
- Compound heterozygous variants in MOGS inducing congenital disorders of glycosylation (CDG) IIb.J Hum Genet. 2019 Mar; 64: 265-268
- ALG11-CDG: three novel mutations and further characterization of the phenotype.Mol Genet Metab Rep. 2015 Mar; 2: 16-19
- PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia.Am J Hum Genet. 2014 Jul 3; 95: 96-107
- Large deletion in PIGL: a common mutational mechanism in CHIME syndrome?.Genet Mol Biol. 2018 Mar; 41: 85-91
- Spondyloocular syndrome: novel mutations in XYLT2 gene and expansion of the phenotypic spectrum.J Bone Miner Res. 2016; 31: 1577-1585
- Auditory characteristics in patients with mucopolysaccharidosis.Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol. 2019; 40: e955-e961
- ENT and mucopolysaccharidoses.Ital J Pediatr. 2018 Nov 16; 44: 127
- Assessment of hearing loss by pure-tone audiometry in patients with mucopolysaccharidoses.Mol Genet Metab. 2014 Apr; 111: 533-538
- Audiological findings in children with mucopolysaccharidoses type i-iv.Acta Otorrinolaringol Esp. 2017 Oct; 68: 262-268
- Neurophysiology of hearing in patients with mucopolysaccharidosis type IV.Mol Genet Metab. 2018; 123: 472-478
- Mucopolysaccharidosis VI.Orphanet J Rare Dis. 2010 Apr 12; 5: 5
- Audiometric evaluation in individuals with mucopolysaccharidosis.Clin Sao Paulo Braz. 2018 03; 73: e523
- Clinical and biochemical manifestations of hyaluronidase deficiency.N Engl J Med. 1996 Oct 3; 335: 1029-1033
- The impact of laronidase treatment in otolaryngological manifestations of patients with mucopolysaccharidosis.Braz J Otorhinolaryngol. 2016 Oct; 82: 522-528
- Lysosomal storage diseases.Transl Sci Rare Dis. 2017 May 25; 2: 1-71
- Brain-stem auditory and visual evoked potentials in children with Krabbe disease.Clin Neurophysiol. 2004 Jul; 115: 1653-1656
- Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal cells contribute to hearing loss in neuraminidase 1-deficient mice.Biochim Biophys Acta. 2010 Feb; 1802: 259-268
- Sialidosis: a review of morphology and molecular biology of a rare pediatric disorder.Diagn Basel Switz. 2018 Apr; 25: 8(2)
- Sialidosis type II: expansion of phenotypic spectrum and identification of a common mutation in seven patients.Mol Genet Metab Rep Mol Genet Metab Rep. 2020 Jan 11; 22: 100561
- The biochemistry and clinical features of galactosialidosis.Biochim Biophys Acta. 1994 Feb 22; 1225: 244-254
- Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis-a cross-sectional study.J Inherit Metab Dis. 2019; 42: 295-302
- Galactosialidosis: historic aspects and overview of investigated and emerging treatment options.Expert Opin Orphan Drugs. 2017; 5: 131-141
- Human disorders of peroxisome metabolism and biogenesis.Biochim Biophys Acta. 2016 May; 1863: 922-933
- Inherited ichthyosis: syndromic forms.J Dermatol. 2016 Mar; 43: 252-263
- Refsum disease. 2006 Mar 20 [updated 2015 Jun 11].in: Adam M.P. Ardinger H.H. Pagon R.A. Wallace S.E. LJH Bean Mirzaa G. GeneReviews® [Internet]. University of Washington, Seattle, Seattle (WA)1993–2021
- Refsum’s disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation.J Neurochem. 2002 Mar; 80: 727-735
- The site of the hearing loss in Refsum’s disease.Int J Pediatr Otorhinolaryngol. 2001 Nov 1; 61: 129-134
- Hearing loss in adult Refsum’s disease.Clin Otolaryngol Allied Sci. 2003 Jun; 28: 227-230
- Cochlear implantation in siblings with Refsum’s disease.Ann Otol Rhinol Laryngol. 2017 Aug; 126: 611-614
- Cochlear implantation in Refsum’s disease.Cochlear Implants Int. 2008 Jun; 9: 97-102
- Cochlear implantation in Refsum disease with facial nerve enlargement.Otol Neurotol. 2019; 40: e58-e59
- Refsum’s disease and cochlear implantation.Ann Otol Rhinol Laryngol. 2014 Jun; 123: 425-427
- Lysosomal alpha-N-acetylgalactosaminidase deficiency: a new inherited metabolic disease.Lancet. 1987 Oct 3; 2: 804
- Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria.J Clin Invest. 1991 Aug; 88: 707-711
- Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy.J Clin Invest. 1990 Nov; 86: 1752-1756
- Mild phenotypic expression of alpha-N-acetylgalactosaminidase deficiency in two adult siblings.J Inherit Metab Dis. 1994; 17: 724-731
- Neurologic manifestations of Kanzaki disease.Neurology. 2004 May 11; 62: 1604-1606
- A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Ménière’s syndrome and without mental retardation.Br J Dermatol. 2001 Feb; 144: 363-368
- A new case of Schindler disease.Eur J Case Rep Intern Med. 2019; 6001269
Article info
Publication history
Published online: July 29, 2021
Accepted:
July 15,
2021
Received:
May 2,
2021
Footnotes
☆Funding information: none.
☆☆A protocol was not prepared.
Identification
Copyright
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