435 BILE ACID (BA) TRANSPORT DEFECT: ONE CAUSE OF REFRACTORY INFANTILE DIARRHEA (R.I.D.)

Abstract

A 5 3/4 year old white male with R.I.D. required parenteral alimentation for 27 months. Watery diarrhea (mean fecal wt. 542 gm.) and steatorrhea (mean fecal fat 15.4 gm./day), persistently low serum cholesterol averaging 72 mg% and vitamin B12 malab-sorption have been present since birth. Small intestinal morphology is normal by lipid histochemical and electron microscopic examination. Surgical exploration revealed normal anatomy. Mean intraluminal BA after meal stimulation are 3.70 mM/L for the first meal and 1.01 mM/L for the third meal of the day. Fecal excretion of oral cholic-carboxyl-14C at 20 months was 58% for the first 24 hours vs. 4.8% ± 1.0 in 5 normal controls. Mean fecal aqueous supernatant BA are 1102 μM/24 hours vs. 100.2 μM ± 35.3/24 hours in 5 normal controls. Cholic acid kinetic studies at 64 and 68 months revealed a fractional turnover rate (FTR) of 1.78 and 2.55 days−1, pool size of 21.8 and 49.1 mg/m2 and synthetic rate was 38.9 and 125.2 mg/m2/day respectively. At 64 mos. the chenodeoxycholic pool size was 48.2 mg/m2, FTR was 0.82 days−1 and the synthetic rate was 39.4 mg/m2/day. No secondary BA were present. Very rapid BA turnover, contracted pool sizes, low intraluminal bile salt concentrations, elevated fecal bile salts, absence of secondary BA and abnormal B12 absorption strongly suggests that failure of BA reabsorption and consequent BA deficiency cause this child's R.I.D. and constitute a specific congenital metabolic defect.