Characteristics of Liver Disease in 100 Individuals With Joubert Syndrome Prospectively Evaluated at a Single Center.
J Pediatr Gastroenterol Nutr
; 66(3): 428-435, 2018 03.
Article
in En
| MEDLINE
| ID: mdl-29112083
ABSTRACT
BACKGROUND AND AIMS:
Joubert Syndrome (JS) is a rare, inherited, ciliopathy defined by cerebellar and brainstem malformations and is variably associated with liver, kidney, and ocular dysfunction. This study characterizes the hepatic findings in JS and identifies factors associated with probable portal hypertension.METHODS:
Hundred individuals with JS were prospectively evaluated at the National Institutes of Health Clinical Center. Laboratory tests, imaging, and DNA sequencing were performed. Patients were stratified based on the spleen length/patient height ratio as a marker of splenomegaly, used as a surrogate for probable portal hypertension.RESULTS:
Forty-three patients (43%) had liver involvement based on elevated liver enzymes and/or liver hyperechogenicity and/or splenomegaly. None of the patients had macroscopic liver cysts or bile duct dilatation. Based on the spleen length/patient height ratio, 13 patients were stratified into a probable portal hypertension group. We observed significant elevations in alkaline phosphatase (269 vs 169âU/L, Pâ≤â0.001), alanine aminotransferase (92 vs 42âU/L, Pâ=â0.004), aspartate aminotransferase (77 vs 40âU/L, Pâ=â0.002), and gamma-glutamyl transferase (226 vs 51âU/L, Pâ≤â0.001) in the probable portal hypertension group. Platelets were lower in the probable portal hypertension cohort (229 vs 299â×â10 cells/µL, Pâ=â0.008), whereas synthetic function was intact in both groups. Probable portal hypertension was also more prevalent in patients with kidney disease (Pâ=â0.001) and colobomas (Pâ=â0.02), as well as mutations in the TMEM67 gene (Pâ=â0.001).CONCLUSIONS:
In JS, probable portal hypertension is associated with abnormal hepatic enzymes, as well as presence of kidney disease, coloboma, and/or mutation in TMEM67. These findings may allow early identification of JS patients who have or are more likely to develop liver disease.
Full text:
1
Database:
MEDLINE
Main subject:
Retina
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Abnormalities, Multiple
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Cerebellum
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Eye Abnormalities
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Kidney Diseases, Cystic
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Liver Diseases
Type of study:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
/
Male
Language:
En
Journal:
J Pediatr Gastroenterol Nutr
Year:
2018
Type:
Article