Cholelithiasis in an infant with Klinefelter's syndrome.

ABSTRACT

Cholelithiasis has been reported only rarely in infants. We describe a case of cholelithiasis in a 1-month-old infant with Klinefelter's syndrome. This association has not been previously reported.

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CHOLELITHIASIS is uncommon in childhood and rare in infancy. (1-3) We report a case of cholelithiasis in a 1-month-old infant with Klinefelter's syndrome. To our knowledge, this association has not previously been reported.

CASE REPORT

This male white infant was born to a gravida 2, para 1 39-year-old mother at term. The father was 44 years old and in good health. There was no history of consanguinity. Amniocentesis at 20 weeks' gestation had shown that the infant had a 47,XXY karyotype consistent with Klinefelter's syndrome. Cesarean section was done because the mother had uterine fibroids, and her labor failed to progress. Apgar scores were 9 at 1 minute and 9 at 5 minutes. At birth, the infant weighed 3.6 kg and was 50 cm long. The immediate neonatal course was uneventful. He was not treated with any medication and did not require total parenteral nutrition. There was no blood group incompatibility.

The infant was brought to the emergency department of the Alberta Children's Hospital at 1 month of age with a 1day history of projectile, nonbilious vomiting. He had vomited 2 or 3 times on that day before admission. There was no associated fever or diarrhea. The infant did not have any contact with individuals with gastroenteritis. There was no family history of hemolytic disorders, cholelithiasis, or gallbladder disease. The infant was afebrile and alert, and the findings on physical examination were essentially normal. In particular, the infant was not dehydrated or jaundiced, and no pyloric mass was felt.

On admission, the hemoglobin level was 128 g/L, white blood cell count was 7.4 x [10.sup.9]/L with a normal differential, and platelet count 594 x [10.sup.9]/L. The red cell morphology was normal. Laboratory studies disclosed the following values: serum sodium, 135 mmol/L; potassium, 5 mmol/L; chloride, 100 mmol/L; bicarbonate, 25 mmol/L; glucose, 6.7 mmol/L; urea, 3.5 mmol/L; creatinine, 19 [micro]mol/L; total bilirubin, 16 [micro]mol/L; direct bilirubin, 4 [micro]mol/L; alkaline aminotransferase, 261 IU/L; asparate aminotransferase, 32 IU/L; lactate dehydrogenase, 226 IU/L; alkaline phosphatase, 344 IU/L; lipase, 8 IU/L; triglycerides, 4.67 mmol/L; and cholesterol, 3.19 mmol/L. Abdominal ultrasonography showed a thickened gallbladder with a single echogenic stone in the bladder neck. There was no evidence of pyloric stenosis.

The infant did not vomit after admission to the hospital. He was treated conservatively with Pedialyte (Abbott Laboratories, Abbott Park, Ill); breast-feeding was resumed after 24 hours. He was discharged from the hospital on the third day after admission. Repeated abdominal ultrasonography 2 weeks later showed two echogenic gallstones, with no evidence of pericholecystic edema or thickening of the gallbladder wall.

DISCUSSION

Although rare, cholelithiasis has been detected in infants with increased frequency in the past decade, largely because of widespread access to ultrasonography and improvement of the sensitivity of the procedure. (4) Many risk factors are known to predispose children to cholelithiasis. These risk factors include hemolytic disease, congenital anomalies of the biliary tract, total parenteral nutrition, prolonged fasting, small-bowel resection and short-bowel syndrome, cystic fibrosis, inflammatory bowel disease, intercurrent infection, dehydration, multiple blood transfusions, prematurity, polycythemia, bronchopulmonary dysplasia, hypotension, prenatal calcium supplementation, furosemide or ceftriaxone therapy, hyperbilirubinemia, phototherapy, umbilical catheterization, metachromatic leukodystrophy, and Wilson's disease. (3,5-9) In late childhood and adolescence, obesity, biliary dyskinesia, pregnancy, and the use of oral contraceptives are typical predisposing factors. (10,11)

Cholelithiasis in association with Down syndrome, regardless of whether there is any associated gastrointestinal malformation, has also been described. (12,13) Recently, Aynaci et al (14) performed ultrasonography on 29 children with Down syndrome and found cholelithiasis in 2 (6.9%) of them. Cholelithiasis has not been reported with other chromosomal disorders, however.

Klinefelter's syndrome, a chromosomal disorder with a 47,XXY karyotype, affects 1 in 500 male patients. (15) The disorder is characterized by testicular failure, androgen deficiency, and impaired spermatogenesis. Beuers et al (16) described the occurrence of a hepatic adenoma in a 20-year-old man with Klinefelter's syndrome. Since hepatic adenomas typically occur in women of child-bearing age who use oral contraceptives, the authors suggest that hormonal imbalance might be responsible for the development of the hepatic adenoma. It is not known whether patients with Klinefelter's syndrome are more prone to cholelithiasis, but since our patient was only 1 month old, was otherwise in good health, and did not seem to have any known risk factors, such a possibility does exist. With our report of this case, perhaps more case reports will be forthcoming. Prospective ultrasonographic studies of patients with Klinefelter's syndrome will help to elucidate whether these individuals are prone to cholelithiasis.

References

(1.) Boyle RJ, Sumner TE, Volberg FM: Cholelithiasis in a 3-week-old small premature infant. Pediatrics 1983;71:967-969

(2.) Asabe K, Handa N: Infant cholelithiasis: report of a case. Surg Today 1997; 27:71-75

(3.) St. Vil D, Yazbeck S, Luks FI, et al: Cholelithiasis in newborns and infants. J Pediatr Surg 1992; 27:1305-1307

(4.) Suchet IB, Labatte MF, Dyck CS, et al: Fetal cholelithiasis: a case report and review of the literature. J Clin Ultrasound 1993; 21:198-202

(5.) Ghose I, Stringer MD: Successful nonoperative management of neonatal acute calculous cholecystitis. J Pediatr Surg 1999; 34:1029-1030

(6.) Jacir NN, Anderson KD, Eichelberger M, et al: Cholelithiasis in infancy: resolution of gallstones in three of four infants. J Pediatr Surg 1986; 21:567-569

(7.) Leung AK: Cholelithiasis in a premature infant: association with short-term total parenteral nutrition, Bol Asoc Med P R 1987; 79:105-107

(8.) Powell RW: Pure calcium carbonate gallstones in a two year old in association with prenatal calcium supplementation. J Pediatr Surg 1985; 20:143-144

(9.) Rosenfield N, Grand RJ, Watkins JB, et al: Cholelithiasis and Wilson disease. J Pediatr 1978; 92:210-213

(10.) Rescorla FJ: Cholelithiasis, cholecystitis, and common bile duct stones. Curr Opin Pediatr 1997; 9:276-282

(11.) Schirmer WJ, Grisoni ER, Gauderer MW: The spectrum of cholelithiasis in the first year of life. J Pediatr Surg 1989; 24:1064-1067

(12.) Zarnitsky C, Lhuintre JP, Joly JP, et al: Association d'une maladie de Hirschsprung, d'un diverticule de Meckel et d'une lithiase vesicularie chez une jeune mongolienne. Ann Gastroenterol Hepatol 1988; 24:21-22

(13.) Aughton DJ, Gibson P, Cacciarelli A: Cholelithiasis in infants with Down syndrome: three cases and literature review. Clin Pediatr 1992; 31:650-652

(14.) Aynaci FM, Orhan F, Celep F, et al: Frequency of cardiovascular and gastrointestinal malformations, leukemia and hypothyroidism in children with Down syndrome in Trabzon, Turkey. Turk J Pediatr 1998; 40:103-109

(15.) Smyth CM, Bremner WJ: Klinefelter syndrome. Arch Intern Med 1998; 158:1309-1314

(16.) Beuers U, Richter WO, Ritter MM, et al: Klinefelter syndrome and liver adenoma. J Clin Gastroenterol 1991; 13:214-216

RELATED ARTICLE: KEY POINTS

* Cholelithiasis is rare in infancy.

* A 1-month-old infant with Klinefelter's syndrome was found to have gallstones without any identifiable risk factors for cholelithiasis.

* Patients with Klinefelter's syndrome may be more prone to cholelithiasis.

From the Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta, Canada.

Reprint requests to Alexander K. C. Leung, MBBS, Alberta Children's Hospital, 1820 Richmond Rd SW, Calgary, Alberta, Canada T2T 5C7.