Achalasia as the Harbinger of a Novel Mitochondrial Disorder in Childhood

Chelimsky, Gisela; Shanske, Sara; Hirano, Michio; Zinn, Arthur B.; Cohen, Mark H.; McNeeley, Kevin; Chelimsky, Thomas C.

doi:10.1097/01.mpg.0000155185.38754.ee

Cited by 9 publications

(9 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Possibly, achalasia results from a failure of smooth muscle fibers to relax which may cause a sphincter to remain closed and fail to open when needed. Achalasia is an exceedingly rare GI manifestation of pediatric MIDs but has been occasionally reported in adults [Chelimsky et al 2005; Kornblum et al 2001]. In a 6-year-old female and a 6-month-old male with multiple mtDNA deletions, achalasia was the dominant feature and occurred at 3 and 7 years of age respectively [Chelimsky et al 2005].…”

Section: Resultsmentioning

confidence: 99%

“…Achalasia is an exceedingly rare GI manifestation of pediatric MIDs but has been occasionally reported in adults [Chelimsky et al 2005; Kornblum et al 2001]. In a 6-year-old female and a 6-month-old male with multiple mtDNA deletions, achalasia was the dominant feature and occurred at 3 and 7 years of age respectively [Chelimsky et al 2005]. Gastroesophageal reflux was found only in the male starting at age 6 months [Chelimsky et al 2005].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Finsterer

Frank

2016

Therap Adv Gastroenterol

View full text Add to dashboard Cite

Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy. Rare GI manifestations of MIDs include dry mouth, paradontosis, tracheoesophageal fistula, stenosis of the duodeno-jejunal junction, atresia or imperforate anus, liver cysts, pancreas lipomatosis, pancreatic cysts, congenital stenosis or obstruction of the GI tract, recurrent bowel perforations with intra-abdominal abscesses, postprandial abdominal pain, diverticulosis, or pneumatosis coli. Diagnosing GI involvement in MIDs is not at variance from diagnosing GI disorders due to other causes. Treatment of mitochondrial GI disease includes noninvasive or invasive measures. Therapy is usually symptomatic. Only for myo-neuro-gastro-intestinal encephalopathy is a causal therapy with autologous stem-cell transplantation available. It is concluded that GI manifestations of MIDs are more widespread than so far anticipated and that they must be recognized as early as possible to initiate appropriate diagnostic work-up and avoid any mitochondrion-toxic treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Finsterer

Frank

2016

Therap Adv Gastroenterol

View full text Add to dashboard Cite

show abstract

“…Achalasia is a rare disorder with an annual incidence of 1 case per 100,000, of which childhood achalasia accounts for less than 5% [8]. Therefore, neither pediatric nor adult literature has provided sufficient evidence to conclude that either endoscopic or surgical therapy is superior.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of treatment of childhood achalasia

Lee

Kays

Chen

et al. 2010

Journal of Pediatric Surgery

View full text Add to dashboard Cite

Purpose The optimal management of achalasia in children and adolescents remains unclear. The aim of this study was to review a single institution experience of endoscopic and surgical interventions in children with achalasia. Methods A retrospective review was conducted of the medical records of children treated for achalasia from 1978 to 2008. Patient demographics and interventions were reviewed. Outcomes after procedural intervention were evaluated. Results 35 patients with achalasia were identified, and data were available for 34 (age 13±6 years, male 62%). 18 patients underwent esophageal dilation (ED), and 16 patients underwent Heller myotomy (HM). Follow-up was available for 30 patients (15 ED, 15 HM). There was symptom recurrence in 15/15 ED cases and 8/15 (53%) HM cases (p<0.01). Additional interventions were performed in 14/15 (93%) ED cases and 6/15 (40%) HM cases (p<0.01). Conclusions Heller myotomy may provide more durable long-term outcomes, as defined by symptom recurrence and need for subsequent intervention, and may be considered the procedure of choice.

show abstract

“…Table S3). However, these have been noted as features of mitochondrial disorders either in general or specifically for other genes [Chelimsky et al, 2005;Garcia-Cazorla et al, 2005;Wolny et al, 2009;Gronlund et al, 2010;Schaefer et al, 2013;Mehawej et al, 2014] Thus, we have significantly expanded the phenotypic range for this class of important mitochondrial genes.…”

mentioning

confidence: 99%

Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA SynthetaseIARS2in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome

et al. 2014

View full text Add to dashboard Cite

Mutations in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases are associated with a range of clinical phenotypes. Here, we report a novel disorder in three adult patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia. Using SNP genotyping and whole-exome sequencing, we identified a single likely causal variant, a missense mutation in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl-tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level was reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. This is the first report of clinical findings associated with IARS2 mutations.

show abstract

Achalasia as the Harbinger of a Novel Mitochondrial Disorder in Childhood

Cited by 9 publications

References 17 publications

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Outcomes of treatment of childhood achalasia

Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA SynthetaseIARS2in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome

Contact Info

Product

Resources

About