Background: Bile acid synthesis disorders (BASD) are a group of uncommon metabolic disorders caused by inborn genetic defects in the synthesis of bile acids. Bile acids are a chemical compound that are produced in the liver to promote the flow and excretion of bile in the liver, a key element in absorption of fats and fat-soluble vitamins, and also work in the elimination of cholesterol from the body. Defects in the bile acid synthesis process lead to a failure in creating normal bile acids, resulting in malabsorption of vital nutrients, and the overproduction of hepatotoxic bile acids. BASD can present with features of cholestasis, poor weight gain, steatorrhea, hepatosplenomegaly, malabsorption of fats, and fat-soluble vitamins. If unrecognized and untreated this can eventually progress to cause life-threatening complications such as liver cirrhosis and eventually liver failure. Method/Results: We analyze a case study of 7-month-old female Hispanic twins, who initially presented to Endocrinology with hypocalcemic rickets and failure to thrive. Hypocalcemic vitamin D deficiency rickets is characterized by low serum calcium and phosphorus, elevated alkaline phosphatase and parathyroid hormone, and rachitic changes in the radiography. The twins had serum and radiographically abnormalities consistent with severe rickets and were started on treatment. At their follow-up appointments with Endocrinology, they were not gaining weight and had mildly elevated alanine transaminase of 50 U/Liter and 81 U/Liter (normal 5-45 U/liter), normal aspartate aminotransferase and bilirubin, so were referred to Gastroenterology. A liver work-up was continued that led to analysis of their urine by fast atom bombardment mass spectrometry showing sulfate and glycol-sulfate conjugates that are characteristic of a diagnosis of 3β-hydroxy-Δ5-C27-steroid dehydrogenase (3β-HSDH) deficiency. Its deficiency is the most common inborn error of bile acid synthesis. The genetic analysis of the twins showed this is the first reported case of a defect caused by a Nucleotide change at c.890delT. Treatment with oral bile acid replacement called cholic acid was started at a dose of 10mg/kg/day. Within three months of treatment each child had considerable clinical and biochemical improvement. Conclusion: Bile acid synthesis disorders are a rare disorder, patients initially do not always present with liver disease. It is important to understand that clinical and lab values that assist in the appropriate diagnosis. BASD should be suspected in infantile rickets, particularly in a clinical setting of cholestasis, poor weight gain, liver disease of unknown cause, or abnormalities of fat or fat-soluble vitamin absorption. Early diagnosis and treatment is imperative because bile acid replacement will help with overall improvement of liver function, fat-soluble vitamin deficiency, and weight gain. A thorough work-up and multi-disciplinary approach can improve diagnosis and treatment of a 3β-HSDH deficiency, preventing the complications of cirrhosis and eventually liver failure in these twins.
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Section on Pediatric Trainees| August 01 2019
Intractable Vitamin D Deficiency Rickets in twin siblings
Pediatrics (2019) 144 (2_MeetingAbstract): 831.
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Osman Ahmad, Janaina Nogueira, Ambika Ashraf; Intractable Vitamin D Deficiency Rickets in twin siblings. Pediatrics August 2019; 144 (2_MeetingAbstract): 831. 10.1542/peds.144.2MA9.831
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