Bile Acid Synthesis Disorder Masquerading as Intractable Vitamin D-Deficiency Rickets

Osman Ahmad; Janaina Nogueira; James E. Heubi; Kenneth D. R. Setchell; Ambika P. Ashraf


J Endo Soc. 2019;3(2):397-402. 

In This Article

Abstract and Introduction


Vitamin D-deficiency rickets, not responding to large treatment doses of oral vitamin D, suggest rare receptor mutations, malabsorption, or hepatobiliary dysfunction. We present a set of twins of Hispanic origin who presented with refractory vitamin D-deficiency rickets and failure to thrive (FTT) at 6 months of age. On follow-up, mild elevations in serum alanine transaminases and normal aspartate aminotransferase were noted. Subsequently, patients manifested fat-soluble vitamin deficiencies. More targeted evaluations revealed a diagnosis of 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. Treatment with oral bile acid replacement with cholic acid resolved rickets and promoted weight gain. Bile acid synthesis disorders should be suspected in refractory rickets in infancy, particularly in a clinical setting of FTT, even in the absence of substantial abnormalities in liver-function tests.


Vitamin D-deficiency rickets is biochemically characterized by a low-serum 25-hydroxy vitamin D (25OHD) level, normal- or low-serum calcium, low-serum phosphorous, elevated serum alkaline phosphatase, and increased parathyroid hormone (PTH). Vitamin D is solublized by intraluminal bile acids and is absorbed through the brush border of the intestinal enterocytes, mainly in the jejunum and ileum. Intestinal absorption of vitamin D is impaired in patients with intestinal, pancreatic, and hepatobiliary disorders and disorders of bile acid synthesis (BASD) or secretion.

BASD are a group of autosomal recessively inherited metabolic disorders that impair the hepatic synthesis of primary bile acids from cholesterol. Bile acids synthesized in the liver play a pivotal role in the absorption of fats and fat-soluble vitamins and in the elimination of cholesterol from the body.[1,2] BASD present with disparate phenotypes, including cholestasis, failure to thrive (FTT), steatorrhea, hepatosplenomegaly, malabsorption of fats and fat-soluble vitamins in infants and children, and advanced liver disease in later life.[1,3,4] If undiagnosed, life-threatening complications, such as liver cirrhosis and eventually, liver failure, can occur.

We present a set of twins, presenting at 6-months of age, with refractory vitamin D-deficiency rickets and FTT caused by a BASD. Their cousins, who are affected by the same disorder, only manifested hepatobiliary abnormalities.