Patients and methods

A total of 139 children with DS (age range 1 month to 19 years, median 36 months), from the area around Naples, referred between March and December 1999 were recruited to the study. Abdominal ultrasound examination was performed in 126. Thirteen patients referrred were not studied for various reasons. None had undergone cholecystectomy. The control group consisted of 577 children (age range 1 month to 19 years, median 40 months), living in the same area, referred to our department for problems unrelated to gallstones. None had a known risk factor for cholelithiasis. Their clinical problems included urinary tract infections and/or urinary tract obstruction (145/577), hepatitis B carriers (117/577), recurrent abdominal pain (114/577), disorders of pubertal development (58/577), inborn errors of metabolism (57/577), multiple congenital anomalies (29/577), and others (57/577). The examinations were performed after an eight hour fast, using a real time ultrasound scanner with a 3.5 MHz linear transducer.

Patients were recruited with informed parental consent. The study was approved by the local ethical committee.

Results

Of the 126 patients with DS who underwent abdominal ultrasound examination, six (4.7%) were found to have cholelithiasis. The four girls were aged 6, 12, 18, and 21 months, respectively; both boys were 6 years old. Among the controls, only one (0.2%) 7 year old girl had gallstones. All seven children with cholelithiasis in our study were born at term, were asymptomatic, and did not have identifiable risk factors for gallstones. The six with DS had normal serum bilirubin, haptoglobin, lipase, and ceruloplasmin concentrations, whole blood carboxyhaemoglobin concentration, reticulocyte count, and liver function tests (alkaline phosphatase, aspartate and alanine aminotransferase, γ glutamyltransferase, prothrombin time, and activated partial thromboplastin time).

In the six children with DS and cholelithiasis, abdominalx ray did not show radiopaque gallstones. In five of the six patients there were between two and five gallstones, varying in diameter between 3.5 and 5.2 mm. In two cases gallstones were present in the infundibulum. In one case a single gallstone was present with a diameter of 3.7 mm. There was no evidence of biliary obstruction.

Discussion

Ultrasonography in 3500 neonates without known risk factors for gallstones has indicated a prevalence of cholelithiasis of 0.5%.1 Palasciano and colleagues2 reported a prevalence of 0.13% in a population study of 1570 subjects aged 6–19 years, living in Southern Italy, as were our patients and controls. Nomura and colleagues3 reported that none of 742 Japanese infants and children had gallstones. Gallstone prevalence in adults is known to vary greatly among ethnic groups and geographic regions. We performed a case–control study, because the previous report of Palasciano and colleagues2 only investigated children aged 6–19 years. The prevalence rate of cholelithiasis in our controls was similar to that reported in the general population under 19 years of age.

Our results strongly suggest that paediatric subjects with DS are at increased risk of cholelithiasis. It is of interest that in our series four patients with DS and cholelithiasis were in the first two years of life.

Bocconi et al studied lipid metabolism in DS and showed that trisomy 21 is associated with hypercholesterolaemia during the intrauterine life.6 Its relation with the increased prevalence of cholelithiasis in the first two years of life requires further study.

Cholelithiasis is often asymptomatic or associated with non-specific symptoms (abdominal pain, vomiting, and fever). Complications including acute cholecystitis, cholangitis, biliary or gall bladder perforation, obstructive jaundice, biliary cirrhosis, and gall bladder carcinoma may occur.4 Clinicians should be aware of the increased risk of gallstones and their possible complications in children with DS.