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Vitamin B12) Deficiency in Johanson–Blizzard Syndrome

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Vitamin B12) Deficiency in Johanson–Blizzard Syndrome European Journal of Clinical Nutrition (2013) 67, 1118 & 2013 Macmillan Publishers Limited All rights reserved 0954-3007/13 www.nature.com/ejcn LETTER TO THE EDITOR Pancytopenia from severe cobalamin (Vitamin B12) deficiency in Johanson–Blizzard syndrome European Journal of Clinical Nutrition (2013) 67, 1118; doi:10.1038/ insufficiency and villous atrophy.3 Defective absorption of ejcn.2013.140; published online 31 July 2013 cobalamin may occur in 40–50% of patients with pancreatic insufficiency,5 exact mechanism(s) remain unclear. Proteolytic degradation of non-intrinsic factor-cobalamin binders has been proposed as the pancreas’ primary role in cobalamin metabolism.6 Johanson–Blizzard syndrome is a rare autosomal recessive Additional studies suggest that adequate bicarbonate is necessary disorder characterized by nasal, auditory and dental abnormalities, for pancreatic proteases to function in the intestinal lumen, and 1 there may be interaction between pancreatic enzymes and bile, and exocrine pancreatic insufficiency. These patients require 5 oral pancreatic enzyme replacement and fat-soluble vitamin affecting R binder degradation and cobalamin absorption. supplements.2 In Johanson–Blizzard syndrome, however, ductular output of fluid and electrolytes is preserved.2 Cobalamin (vitamin B12) is essential for several important enzymatic processes in the body that lead to energy metabolism, As patients with exocrine pancreatic insufficiency are on DNA synthesis and blood cell production. Patients with cobalamin fat-soluble vitamin (A,D, E,K) supplements because of steatorrhea deficiency can develop hematological and neuropsychiatric and risk of malabsorption of these vitamins, the clinicians focus on abnormalities. Absorption of cobalamin is complex. Two distinct monitoring the status of these four vitamins. Cobalamin deficiency cobalamin-binding proteins haptocorrin (R binder) and intrinsic is generally not considered. As severe cobalamin deficiency can factor (IF) compete for free cobalamin released in the stomach. occur in patients with Johanson–Blizzard syndrome with exocrine In the acidic environment, haptocorrin binds free cobalamin pancreatic insufficiency, routine monitoring of cobalamin status with much greater affinity than IF. Pancreatic enzymes degrade with serum cobalamin, homocysteine and methylmalonic the haptocorrin–cobalamin complex in the small intestine, acid levels is recommended for early detection of this deficiency releasing free cobalamin to bind to IF for its eventual absorption to avert serious, potentially life-threatening complications. in the terminal ileum.3 Cobalamin deficiency can occur rarely in patients with exocrine pancreatic insufficiency (for example, cystic fibrosis), although the precise mechanisms remain unclear.4 CONFLICT OF INTEREST We report this complication occurring in Johanson–Blizzard The authors declare no conflict of interest. syndrome. A 19-year-old male with known Johanson–Blizzard syndrome S Aubrey1, B Crooks2 and M Rashid1 presented with progressive fatigue, anorexia and weight loss. 1Division of Gastroenterology and Nutrition, Department of He was diagnosed with Johanson–Blizzard syndrome in infancy Paediatrics, Faculty of Medicine, Dalhousie University, IWK Health and had hypoplasia of alae nasi, hearing deficit (requiring aids), Centre, Halifax, Nova Scotia, Canada and visual impairment, hypodontia (later) and exocrine pancreatic 2Division of Haematology and Oncology, Department of Paediatrics, insufficiency. Over the years, he was followed regularly and had Faculty of Medicine, Dalhousie University, IWK Health Centre, done generally well with oral pancreatic enzymes and fat-soluble Halifax, Nova Scotia, Canada vitamin supplements. Assessment revealed marked pallor, severe E-mail: [email protected] pancytopenia, decreased serum vitamin B12 level and markedly elevated serum homocysteine and methylmalonic acid. Serum ferritin, folate and vitamin E levels were normal. Bone marrow REFERENCES aspirate revealed hypercellularity but no malignancy. He required 1 Rezaei N, Sabbaghian M, Liu Z, Zenker M. Johanson-Blizzard syndrome. Eur J Pediatr a blood transfusion and received intramuscular vitamin B12 daily. 2011; 170: 179–183. The pancytopenia rapidly improved and peripheral smear normal- 2 Jones NL, Hofley PM, Durie PR. Pathophysiology of the pancreatic defect in ized. He was discharged on oral vitamin B12 supplements. Johanson-Blizzard syndrome: A disorder of acinar development. J Pediatr 1994; At follow-up 6 weeks later, symptoms had resolved, weight 125: 406–408. 3 Langan RC, Zawistoski KJ. Update on vitamin B deficiency. Am Fam Physician improved, and blood counts and vitamin B12 level normalized. Six 12 2011; 83: 1425–1430. months later the patient remained well on oral vitamin B12 supplements with normal blood indices and cobalamin status. 4 Rucker RW, Harrison GM. Vitamin B12 deficiency in cystic fibrosis. NEJM 1973; 289: 329. Causes of cobalamin deficiency include strict vegetarianism, 5 Bernstein L, Herbert V. The role of pancreatic exocrine secretions in the absorption hypochlorhydria (gastrectomy, pernicious anemia), ileal resection, of vitamin B12 and iron. J Clin Nutr 1973; 26: 340–346. small bowel bacterial overgrowth, congenital deficiency in 6 Herzlich B, Herbert V. The role of the pancreas in cobalamin (vitamin B12) transcobalamin II and malabsorptive states such as pancreatic absorption. Am J Gastroenterol 1984; 79: 489–493..
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