Cobalaminmangel bei Hund und Katze

Franziska Hanisch; Linda Toresson; Thomas Spillmann

doi:10.15654/TPK-180458

Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere, Table of Contents

Tierarztl Prax Ausg K Kleintiere Heimtiere 2018; 46(05): 309-314
DOI: 10.15654/TPK-180458

Übersichtsartikel – Review Article

Georg Thieme Verlag KG Stuttgart · New York

Cobalaminmangel bei Hund und Katze

Cobalamin deficiency in dogs and cats

Authors

Franziska Hanisch

¹Tierarztpraxis Dr. Deicke, Halberstadt
Linda Toresson

²Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, Helsinki University, Finland

³Evidensia Specialist Animal Hospital, Helsingborg, Sweden
Thomas Spillmann

²Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, Helsinki University, Finland

Abstract

Zusammenfassung

Cobalamin ist ein Vitamin der B-Gruppe und als Kofaktor an Stoffwechselabläufen wie der Nukleinsäuresynthese, der Aminosäuresynthese und dem Zitratzyklus beteiligt. Da Säugetiere Cobalamin nicht selbst synthetisieren können, sind sie auf die Zufuhr über die Nahrung angewiesen. Die Resorption des Vitamins setzt bei Hund und Katze ein funktionales exokrines Pankreas voraus. Sie erstreckt sich über Magen und Duodenum bis hin zum Ileum und stellt einen äußerst komplexen Prozess dar. Somit kann eine Fülle gastrointestinaler Erkrankungen wie z. B. chronische Enteropathien, intestinales Lymphom oder exokrine Pankreasinsuffizienz zur Hypocobalaminämie führen. Ferner wurde bei einigen Hunderassen (Riesenschnauzer, Border Collie, Australian Shepherd und Beagle) ein primärer, hereditärer Cobalaminmangel (Imerslund-Gräsbeck-Syndrom) nachgewiesen. Zu den klinischen Sympto men einer Hypocobalaminämie zählen Inappetenz, Erbrechen, Diarrhö, Wachstumsstörungen und neuronale Defizite. Als labordiagnostische Veränderungen wurden nichtregenerative Anämie, Leukopenie, Hypoglykämie und Hyperammonämie beschrieben. Bei Verdacht auf einen Cobalaminmangel wird die Vitaminkonzentration bei Hund und Katze üblicherweise mittels Immunoassay im Blut gemessen. Da jedoch Blut- und Zellgehalt des Vitamins differieren können, ist die isolierte Cobalaminmessung in ihrer Aussagekraft limitiert. Die Therapie hängt in erster Linie von der Primärerkrankung ab und hat zum Ziel, die Ursache der Hypocobalaminämie zu beseitigen. Oftmals zeigt sich ein Behandlungserfolg der gastrointestinalen Erkrankung allerdings erst dann, wenn zusätzlich parenteral oder oral Cobalamin verabreicht wird. Bei Patienten mit Imerslund-Gräsbeck-Syndrom ist die regelmäßige und lebenslange Substitution essenziell.

Summary

Cobalamin is a member of the B-group of vitamins and a cofactor for metabolic processes like nucleic acid synthesis, amino acid synthesis, and the citric acid cycle. Mammals are unable to synthesize cobalamin and therefore rely on adequate food intake. Cobalamin absorption is a complex process in the stomach, duodenum, and ileum, requiring a functional exocrine pancreas. Thus, a great number of gastrointestinal diseases like chronic enteropathies, intestinal lymphoma, or exocrine pancreatic insufficiency can lead to hypocobalaminemia. Furthermore, some dog breeds (Giant Schnauzer, Border Collie, Australian Sheperd Dog, and Beagle) can have a primary, hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome). Clinical signs of cobalamin deficiency comprise anorexia, vomiting, diarrhoea, failure to thrive, and neuropathies. Laboratory findings like non-regenerative anemia, leukopenia, hypoglycemia, and hyperammonaemia have also been described. When hypocobalaminemia is suspected usually in dogs and cats, the cobalamin concentration is usually measured by immunoassay. Because the concentrations of cobalamin in blood and cells can differ the sole measurement of the vitamin concentration is of limited informative value. Treatment depends on the underlying disease aiming at eliminating the cause of hypocobalaminemia. However, successful therapy of gastrointestinal diseases often requires an additional oral or parenteral cobalamin supplementation. In patients with Imerslund-Gräsbeck syndrome, a regular and lifelong cobalamin supplementation is essential.

Schlüsselwörter

Vitamin B₁₂ - Hypocobalaminämie - Imerslund-Gräsbeck-Syndrom - Methylmalonsäure - Homozystein

Keywords

Vitamin B₁₂ - hypocobalaminemia - Imerslund-Gräsbeck syndrome - methyl malonic acid - homocysteine

Full Text

References

Literatur
1 Allenspach K, Wieland B, Gröne A, Gaschen F. Chronic enteropathies in dogs: Evaluation of risk factors for negative outcome. J Vet Intern Med 2007; 21: 700.
2 Banerjee R. B12 trafficking in mammals: A for coenzyme escort service. ACS Chem Biol 2006; 01: 149-159.
3 Batchelor DJ, Noble PM, Taylor RH, Cripps PJ, German AJ. Prognostic factors in canine exocrine pancreatic insufficiency: Prolonged survival is likely if clinical remission is achieved. J Vet Intern Med 2007; 21: 54.
4 Batt RM, Horadagoda NU, McLean L, Morton DB, Simpson KW. Identification and characterization of a pancreatic intrinsic factor in the dog. Am J Physiol 1989; 256: 517-523.
5 Battersby IA, Giger U, Hall EJ. Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border Collie. J Small Anim Pract 2005; 46: 392-395.
6 Berghoff N, Suchodolski JS, Steiner JM. Association between serum cobalamin and methylmalonic acid concentrations in dogs. Vet J 2012; 191: 306-311.
7 Berghoff N, Parnell NK, Hill SL, Suchodolski JS, Steiner JM. Serum cobalamin and methylmalonic acid concentrations in dogs with chronic gastrointestinal disease. Am J Vet Res 2013; 74: 84-89.
8 Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med Scand 1968; 184: 247-258.
9 Carmel R, Green R, Rosenblatt DS, Watkins D. Update on cobalamin, folate and homocysteine. Hematology 2003; (01) 62-81.
10 Fordyce HH, Callan MB, Giger U. Persistent cobalamin deficiency causing failure to thrive in a juvenile beagle. J Small Anim Pract 2000; 41: 407-410.
11 Fowler B. Genetic defects of folate and cobalamin metabolism. Eur J Pediatr 1998; 157: 60-66.
12 Fyfe JC, Jezyk PF, Giger U. et al. Inherited selective malabsorption of vitamin B12 in Giant Schnauzers. J Am Anim Hosp Assoc 1989; 25: 533-539.
13 Fyfe JC, Hall CA, Jezyk PF, Klumpp SA, Levine JS, Patterson DF. Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs. Pediatr Res 1991; 39: 24-31.
14 Fyfe JC. Feline intrinsic factor (IF) is pancreatic in origin and mediates ileal cobalamin (CBL) absorption. J Vet Intern Med 1993; 07: 133.
15 Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, De la Chapelle A, He QC, Moestrup SK. The functional cobalamin-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood 2004; 103: 1573-1579.
16 Fyfe JC, Hemker SL, Venta PJ. et al. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs. Mol Genet Metab 2013; 109: 390-396.
17 Fyfe JC, Hemker SL, Venta PJ, Stebbing B, Giger U. Selective intestinal cobalamin malabsorption with proteinuria (Imerslund-Gräsbeck Syndrome) in juvenile beagles. J Vet Intern Med 2014; 28: 356-362.
18 Gold AJ, Scott MA, Fyfe JC. Failure to thrive and life-threatening complications due to inherited selective cobalamin malabsorption effectively managed in a juvenile Australian shepherd dog. Can Vet J 2015; 56: 1029-1034.
19 Gołyński M, Lutnicki K, Krumrych W, Szczepanik M, Gołyńska M, Wilkołek P, Adamek Ł, Sitkowski Ł, Kurek Ł. Relationship between total homocysteine, folic acid, and thyroid hormones in hypothyroid dogs. J Vet Intern Med 2017; 31: 1403-1405.
20 Gräsbeck R, Gordin R, Kantero I, Kuhlback B. Selective cobalamin malabsorption and proteinuria in young people. Acta Med Scand 1960; 167: 289-296.
21 Grützner N, Bishop MA, Suchodolski JS, Steiner JM. Association study of cobalamin deficiency in the Chinese Shar Pei. J Hered 2010; 101: 211-217.
22 Grützner N, Heilmann RM, Stupka KC, Rangachari VR, Weber K, Holzenburg A, Suchodolski JS, Steiner JM. Serum homocysteine and methylmalonic acid concentrations in Chinese Shar-Pei dogs with cobalamin deficiency. Vet J 2013; 197: 420-426.
23 He Q, Madsen M, Kilkenney A. et al. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin absorption in vivo. Blood 2005; 106: 1447-1453.
24 Imerslund O. Idiopathic chronic megaloblastic anemia in children. Acta Paediatr Scand 1960; 49: 1-115.
25 Jugan MC, August JR. Serum cobalamin concentrations and small intestinal ultrasound changes in 75 cats with clinical signs of gastrointestinal disease: a retrospective study. J Feline Med Surg 2017; 19: 48-56.
26 Kempf J, Hersberger M, Mellinger RH, Reusch CE, Kook PH. Effects of 6 weeks of parenteral cobalamin supplementation on clinical and biochemical variables in cats with gastrointestinal disease. J Vet Intern Med 2017; 31: 1664-1672.
27 Kempf J, Melliger RH, Reusch CE, Kook PH. Effects of storage conditions and duration on cobalamin concentration in serum samples from cats and dogs. J Am Vet Med Assoc 2018; 252: 1368-1371.
28 Kiefer I, Rieder A. Homocystein und Hyperhomocysteinämie. J Kardiol 2001; 08: 58-63.
29 Kook PH, Zerbe P, Reusch CE. Exocrine pancreatic insufficiency in the cat. Schweiz. Arch. Tierheilk 2011; 153: 19-25.
30 Kook PH, Lutz S, Sewell AC, Bigler B, Reusch CE. Untersuchungen zur Serumcobalaminkonzentration bei Katzen mit gastrointestinaler Symptomatik. Schweiz Arch Tierheilk 2012; 154: 479-486.
31 Kook PH, Reusch CE, Hersberger M. Prospective long-term evaluation of parenteral hydroxocobalamin supplementation in juvenile beagles with selective intestinal cobalamin malabsorption (Imerslund-Gräsbeck syndrome). J Vet Intern Med 2018; 32: 1033-1040.
32 Lutz S, Sewell AC, Reusch CE, Kook PH. Clinical and laboratory findings in Border Collies with presumed hereditary juvenile cobalamin deficiency. J Am Anim Hosp Assoc 2013; 49: 197-203.
33 Morgan LW, McConnell J. Cobalamin deficiency associated with erythroblastic anemia and methylmalonic aciduria in a border collie. J Am Anim Hosp Assoc 1999; 35: 392-395.
34 Obeid R. Methylmalonsäure: Ein Biomarker für Vitamin B12-Mangel. Dialog 2014; 1-3.
35 Patterson BE, Barr JW, Fosgate GT, Berghoff N, Steiner JM, Suchodolski JS, Black DM. Homocysteine in dogs with systemic inflammatory response syndrome. J Small Anim Pract 2013; 54: 620-624.
36 Rossi S, Rossi G, Giordano A, Paltrinieri S. Homocysteine measurement by an enzymatic method and potential role of homocysteine as a biomarker in dogs. J Vet Diagn Invest 2008; 20: 644-649.
37 Ruaux CG, Steiner JM, Williams DA. Metabolism of amino acids in cats with severe cobalamin deficiency. Am J Vet Res 2001; 62: 1852-1858.
38 Ruaux CG, Steiner JM, Williams DA. Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia. J Vet Intern Med 2005; 19: 155-160.
39 Ruaux CG. Laboratory tests for the diagnosis of intestinal disorders. In: Small Animal Gastroenterology. Steiner JM. ed. Hannover: Schlütersche; 2008: 50-55.
40 Ruaux CG, Steiner JM, Williams DA. Relationships between low serum cobalamin concentrations and methylmalonic acidemia in cats. J Vet Intern Med 2009; 23: 472-475.
41 Ruaux CG. Cobalamin in companion animals: Diagnostic marker, deficiency states and therapeutic implications. Vet J 2013; 196: 145-152.
42 Senger VG. Wissenschaftliche Bewertung des Einsatzes von Vitaminen und ausgewählten Antioxidanzien in der Ernährung von Katzen, Hunden und Pferden: Anspruch und Wirklichkeit. Dissertation: Tierärztliche Fakultät der Ludwig-Maximilians-Universität München; 2004
43 Solomon LR. Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev 2007; 21: 113-130.
44 Toresson L, Steiner JM, Suchodolski JS, Spillmann T. Oral cobalamin supplementation in dogs with chronic enteropathies and hypocobalaminemia. J Vet Intern Med 2016; 30: 101-107.
45 Toresson L, Steiner JM, Olmedal G, Larsen MB, Suchodolski JS, Spillmann T. Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study. J Feline Med Surg 2017; 19: 1302-1306.
46 Toresson L, Steiner JM, Razdan P, Spodsberg E, Olmedal G, Suchodolski JS, Spillmann T. Comparison of efficacy of oral and parenteral cobalamin supplementation in normalising low cobalamin concentrations in dogs: A randomised controlled study. Vet J 2018; 232: 27-32.
47 Volkmann M, Steiner JM, Fosgate GT, Zentek J, Hartmann S, Kohn B. Chronic diarrhea in dogs – retrospective study in 136 cases. J Vet Intern Med 2017; 31: 1043-1055.
48 Worhunsky P, Toulza O, Rishniw M, Berghoff N, Ruaux CG, Steiner JM, Simpson KW. The relationship of serum cobalamin to methylmalonic acid concentrations and clinical variables in cats. J Vet Intern Med 2013; 27: 1056-1063.