Congenital bile acid malabsorption is a rare, autosomal recessive disease caused by mutations in the ileal sodium bile acid cotransporter. This condition occurs in the first few months of life and is associated with failure to thrive, diarrhea, steatorrhea, and in few cases, deficiencies of fat-soluble vitamins. To our knowledge, the following case is the first reported incidence of hemorrhagic vitamin K deficiency secondary to bile acid malabsorption.

Case Presentation

A 16-week-old Amish male infant was brought to the hospital with a 3-day history of intermittent vomiting, decreased oral intake, and lethargy. He was delivered vaginally with no prenatal complications to a 20-year-old healthy mother who had no significant medical history. The mother had received routine prenatal care, and the baby was reported to have been delivered with a midwife, at home. The birth weight was 3187 g, and physical examination findings were normal immediately after delivery. He received vitamin K at birth, and until this illness was breast feeding well. His weight gain was 28 g/day, and he was developing normally. He had not received any immunizations.

The infant was admitted to the hospital. Three days earlier, he had vomited 4 to 5 times throughout the day, not in association with feedings. During the next 3 days, the vomiting increased in frequency, and he became less alert and responsive and was sleeping excessively. On the morning of presentation he had 2 episodes of coffee ground emesis and was increasingly lethargic.

Physical examination revealed a lethargic but arous-able, afebrile, mildly hypotonic infant. His heart rate was 140 to 170 beats/min, and his anterior fontanelle was noted to be bulging; the remainder of the examination was normal. Initial laboratory studies, including serum electrolytes and chest radiography, were normal.

Figure—Head CT scan showing large right frontoparietal intracranial hemorrhage with effacement of the right lateral ventricle and significant midline shift.

A complete blood cell count was normal, except for a hemoglobin of 12.8 g/dL (normal, 13.5-17 g/dL). Coagulation studies revealed a prothrombin time (PT) of 24.5 seconds and a partial thromboplastin time (PTT) of 72 seconds. Fibrinogen level and liver function studies, including bilirubin level, were normal. Levels of factors II, VII, IX, and X were low. A computed tomography (CT) scan of the head revealed a large right frontoparietal intracranial bleed, with effacement of the right lateral ventricle and significant midline shift (Figure). A skeletal survey excluded trauma, and an ophthalmologic examination was normal. Further questioning of the parents revealed that a paternal cousin had died at age 7 months from chronic diarrhea secondary to bile acid transporter defects.

The diagnosis of congenital bile acid malabsorption was confirmed in our patient by a positive selenohomocholic acid taurine test. He was given vitamin K and 2 units of fresh frozen plasma, which immediately normalized the coagulation parameters. Neurosurgical decompression was achieved with a ventricular shunt, and repeat CT scans in the next 2 weeks showed no further bleeding and gradual reductions in midline shift and ventriculomegaly. The infant resumed breast feeding, and was discharged home at age 24 weeks.

Discussion

The causes associated with intracranial bleeding in an infant vary widely (Table). The most common differential diagnoses for an intracranial bleed in a 4-month-old infant include trauma, congenital vascular anomalies, bleeding disorders, and intrapartum or perinatal insult. More rare etiologies include other causes of stroke, platelet disorders, and platelet glycoprotein receptor abnormalities.

Prolonged PT in infants is generally a result of congenital or acquired factor VII deficiency or an underlying liver disease, such as alpha₁-antitrypsin deficiency, Alagille syndrome, or biliary tree abnormalities. The most common causes of combined PT and PTT prolongation include disseminated intravascular coagulation, liver disease, and inherited or acquired deficiencies of prothrombin, fibrinogen, factor V, and factor X.

Congenital bile acid malabsorption is a rare, autosomal recessive disease caused by mutations in the ileal sodium bile acid cotransporter. It usually affects infants in the first few months of life, manifested as chronic diarrhea and steatorrhea as a result of the inability to properly absorb and process lipids.^1-3 Bile acids are critical for intestinal digestion of lipids and for assimilation of lipid-soluble nutrients and vitamins. This inability to properly absorb and process lipids leads to a fat-losing state, resulting in the infant’s failure to thrive. This condition can also present with signs and symptoms similar to cystic fibrosis; therefore, a sweat test should always be performed in an infant with chronic diarrhea and steatorrhea.

Bile acid malabsorption states must also be distinguished from intrinsic biliary tree disorders, such as biliary atresia, choledochal cysts, as well as other genetic bile duct anomalies, including Alagille syndrome, characterized by the absence of cholestasis, and conjugated hyperbilirubinemia.^2,4,5 Infants with bile acid malabsorption states have normal biliary tree anatomy and no evidence of intrahepatic or gallbladder involvement.

Vitamin K, along with vitamins A, D, and E, comprise the 4 lipid-soluble vitamins absorbed in the gastrointestinal tract. Symptoms of vitamin K deficiency occur within the first 48 to 72 hours of life, and factor levels usually return to normal by day 7 to 10 without treatment as a result of intrahepatic synthesis of vitamin K. In rare cases, vitamin K deficiency presents with vitamin K deficiency bleeding (previously referred to as “hemorrhagic disease of the newborn”)⁶ during the first week of life, with an incidence of 0.25% to 1.7%.⁶ This results from transient deficiencies of vitamin K-dependent factors II, VI, IX, and X. Vitamin K deficiency bleeding is characterized by gastrointestinal, nasal, subgaleal, or intracranial hemorrhage. Such infants also may develop severe osteomalacia and early-onset rickets secondary to vitamin D deficiency in the first year of life.⁶

Treatment is accomplished by vitamin A, D, E, and K supplementation. The American Academy of Pediatrics now recommends giving all newborns a 0.5 to 1.0 mg intramuscular dose of vitamin K to prevent vitamin K deficiency bleeding.⁶

Patients with mild-to-moderate bile acid malabsorption generally respond well to bile acid binders, such as cholestyramine. Those with severe congenital malabsorption require lifelong supplementation with medium-chain triglycerides and a low-fat diet.¹ In addition, cholylsarcosine may be used as replacement therapy, although efficacy may be limited.²

Conclusion

Infants with bile acid malabsorption disorders present within the first few months of life with signs of vitamin K deficiency. With early recognition and prompt treatment, rapid resolution of the coagulopathy occurs and normal growth and development is expected.

References

1. Westergaard H. Bile acid malabsorption. Curr Treat Options Gastroenterol. 2007;10:28-33.
2. Eusufzai S. Bile acid malabsorption: mechanisms and treatment. Dig Dis. 1995;13:312-321.
3. Oelkers P, Kirby LC, Heubi JE, et al. Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J Clin Invest. 1997;99:1880-1887.
4. Kamath BM, Piccoli DA. Heritable disorders of the bile ducts. Gastroenterol Clin North Am. 2003;32:857-875, vi.
5. Tomer G, Shneider BL. Disorders of bile formation and biliary transport. Gastroenterol Clin North Am. 2003;32:839-855, vi.
6. American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. Pediatrics. 2003; 112:191-192.