19307547 Visualization

A newborn Age boy Sex of healthy Family_history nonconsanguineous Family_history parents Family_history was delivered Clinical_event at 37 Date weeks’ Date gestation Date by cesarean Therapeutic_procedure section Therapeutic_procedure .
His mother Subject ( primipara Family_history , 32 Family_history years Family_history old Family_history ) had been admitted Clinical_event to our hospital Nonbiological_location 2 Date weeks Date previously Date because of reduced Lab_value fetal Sign_symptom intrauterine Sign_symptom movements Sign_symptom and polyhydramnios Sign_symptom .
The child’s birthweight Diagnostic_procedure was 2,330 Lab_value g Lab_value ( <10th Lab_value percentile Lab_value ), length Diagnostic_procedure 47 Lab_value cm Lab_value , and head Diagnostic_procedure circumference Diagnostic_procedure 33.2 Lab_value cm Lab_value (25th percentile).
He had low Sign_symptom - set Sign_symptom ears Sign_symptom and bilateral Sign_symptom clubfoot Sign_symptom .
Apgar Diagnostic_procedure scores Diagnostic_procedure were 2 Lab_value , 6 Lab_value , and 7 Lab_value at 1 Time , 5 Time , and 10 Time minutes Time .
The child presented Clinical_event with severe Severity hypotonia Sign_symptom and generalized Sign_symptom muscle Sign_symptom weakness Sign_symptom , requiring ventilatory Therapeutic_procedure assistance Therapeutic_procedure and total Therapeutic_procedure parenteral Therapeutic_procedure nutrition Therapeutic_procedure .
Weaning failed because of inadequate pulmonary ventilation and respiratory Disease_disorder acidosis Disease_disorder .
Hearing Sign_symptom loss Sign_symptom was detected by auditory Diagnostic_procedure evoked Diagnostic_procedure potentials Diagnostic_procedure , while cranial Biological_structure MRI Diagnostic_procedure showed mildly Lab_value enlarged Lab_value ventricles Biological_structure and liquor Biological_structure spaces Biological_structure .
Two Date days Date after Date birth Date , the infant presented with severe Severity abdominal Sign_symptom distension Sign_symptom with a hypoactive Sign_symptom bowel Sign_symptom .
MRI Diagnostic_procedure revealed marked Severity intestinal Sign_symptom dilation Sign_symptom without mechanical Sign_symptom obstruction Sign_symptom .
Laboratory Diagnostic_procedure investigations Diagnostic_procedure showed hypoglycemia Sign_symptom ( 27 Lab_value mg/dL Lab_value ), hypomagnesemia Sign_symptom ( 0.58 Lab_value mmol/L Lab_value ), and hypokalemia Sign_symptom ( 2.4 Lab_value mmol/L Lab_value ).
Blood Diagnostic_procedure lactate Diagnostic_procedure was normal Lab_value ( 1.3 Lab_value mmol/L Lab_value , normal Detailed_description range Detailed_description 0.5–2.2 mmol/L Detailed_description ) and liver Diagnostic_procedure enzymes Diagnostic_procedure were unremarkable Lab_value .
A skeletal Biological_structure muscle Biological_structure biopsy Diagnostic_procedure was performed and showed scattered Detailed_description , hypertrophic Detailed_description cytochrome Diagnostic_procedure c Diagnostic_procedure oxidase Diagnostic_procedure (COX)-deficient and succinate Diagnostic_procedure dehydrogenase Diagnostic_procedure – positive Lab_value muscle Biological_structure fibers Biological_structure (figure), suggesting a mitochondrial Disease_disorder disorder Disease_disorder .
Molecular Diagnostic_procedure genetic Diagnostic_procedure studies Diagnostic_procedure revealed marked Severity mtDNA Sign_symptom depletion Sign_symptom in muscle ( 93% Lab_value decrease Lab_value as compared Detailed_description to Detailed_description age Detailed_description - matched Detailed_description controls Detailed_description ), while a screen Diagnostic_procedure for Diagnostic_procedure mtDNA Diagnostic_procedure rearrangements Diagnostic_procedure within individual Biological_structure COX Biological_structure - positive Biological_structure and COX Biological_structure - deficient Biological_structure fibers4 was negative Lab_value .
We sequenced Diagnostic_procedure the entire Detailed_description coding Detailed_description region Detailed_description and Detailed_description intron Detailed_description - exon Detailed_description boundaries Detailed_description of the POLG1 Biological_structure gene Biological_structure , identifying two Lab_value reported heterozygous Sign_symptom missense Sign_symptom mutations Sign_symptom in compound c.679C>T Sign_symptom predicting Sign_symptom p.R227W Sign_symptom and c.2542G>A Sign_symptom predicting Sign_symptom p.G848S.
Sequencing Diagnostic_procedure of Diagnostic_procedure parental Diagnostic_procedure samples Diagnostic_procedure confirmed recessive Sign_symptom inheritance Sign_symptom .
The infant died Outcome at 20 Date days Date of respiratory Disease_disorder failure Disease_disorder .
At autopsy Diagnostic_procedure , the brain Biological_structure did not show remarkable Sign_symptom changes Sign_symptom on gross Diagnostic_procedure examination Diagnostic_procedure .
Histology Diagnostic_procedure was not informative due to poor preservation of tissue; there was no evidence of neuronal Sign_symptom damage Sign_symptom in the spinal Biological_structure cord Biological_structure .
The liver Biological_structure showed diffuse Detailed_description cholestasis Sign_symptom , consistent with total parenteral nutrition; hepatocyte Biological_structure steatosis Sign_symptom , necrosis Sign_symptom , or liver Biological_structure fibrosis Sign_symptom were not observed.
The testicles were undescended, while remaining visceral organs were normal except for a marked dilation Sign_symptom and thinning Sign_symptom of the bowel Biological_structure wall Biological_structure .
Despite normal histology, analysis of stomach Biological_structure , ileum Biological_structure , and colon Biological_structure homogenates Biological_structure revealed severe Severity mtDNA Sign_symptom depletion Sign_symptom ( up Lab_value to Lab_value 94% Lab_value decrease Lab_value ; table e-1 on the Neurology® Web site at www.neurology.org).
Laser Diagnostic_procedure capture Diagnostic_procedure microdissection Diagnostic_procedure analysis5 revealed that the mtDNA Coreference depletion Coreference was confined to the muscularis Biological_structure propria Biological_structure , being most prominent in its external Detailed_description layer Detailed_description (figure).
Ganglion Biological_structure cells Biological_structure from the myenteric Biological_structure plexus Biological_structure showed milder Severity mtDNA Coreference depletion Coreference , restricted to the small Biological_structure intestine Biological_structure (figure).
There was no mtDNA Sign_symptom depletion Sign_symptom in liver Biological_structure (not shown).