Abstract
Metabolic studies are described in a patient who presented at 3 weeks of age with severe anaemia, hyperbilirubinaemia and hypotonicity. Clinically, glycogen storage disease type II (Pompe disease) was suspected because of a massively enlarged heart and hepatosplenomegaly. This was confirmed biochemically by the demonstration of glycogen accumulation in skeletal muscle and undetectable acid α-1,4-glucosidase activity in fibroblasts. Further biochemical studies in this patient surprisingly revealed homocystinuria and methylmalonic aciduria, suggesting a defect in the uptake, transport or intracellular metabolism of vitamin B12. Studies in cultured fibroblasts from the patient revealed a low uptake of [57Co]cyanocobalamin and an impaired intracellular conversion to both 5′-deoxyadenosylcobalamin and methylcobalamin. Moreover, the incorporation of labelled propionate into proteins as well as the formation of labelled methionine from labelled 5-methyltetrahydrofolate was deficient in fibroblasts from the patient. Complementation studies revealed the presence of the cblC mutation in this patient. No treatment was initiated and the patient died at the age of 31 days. We conclude that the patient was affected by both glycogen storage disease type II and cblC disease. The remarkable combination of these two rare inborn errors can be the result of the consanguinity of the parents.
Similar content being viewed by others
Abbreviations
- AdoCbl:
-
5′-deoxyadenosylcobalamin
- MeCbl:
-
Methylcobalamin
References
Batholomew DW, Allen RH, Roe CR, Rosenblatt DS, Valle DL, Francomano CA, Batshaw ML (1988) Therapeutic approaches to cobalamin-C methylmalonic acidemia and homocystinuria. J Pediatr 112:32–39
Cooper BA, Rosenblatt DS (1987) Inherited defects of vitamin B12 metabolism. Ann Rev Nutr 7:291–320
Fenton WA, Rosenberg LE (1989) Inherited disorders of cobalamin transport and metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 2065–2082
Fusch C, Huenges R, Moser HW, Sewell AC, Roggendorf W, Kustermann-Kuhn B, Poulos A, Carey WF, Harzer K (1989) A case of combined Farber and Sandhoff disease. Eur J Pediatr 148:558–562
Goodman SI, Moe PG, Hammond KB, Mudd SH, Uhlendorf BW (1970) Homocystinuria with methylmalonic aciduria: Two cases in a sibship. Biochem Med 4:550–515
Halley DJJ, Konings A, Hupkes P, Galjaard H (1984) Regional mapping of the human gene for lysosomal α-glucosidase by in situ hybridization. Hum Genet 67:326–328
Hers HG (1963) α-glucosidase deficiency in generalized glycogen storage disease (Pompe's disease). Biochem J 86:1–6
Hers HG, Van Hoof F, De Barsel T (1989) Glycogen storage disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease 6th edn. McGraw-Hill, New York, pp 425–452
Reuser AJJ, Koster JF, Hoogeveen A, Galjaard H (1978) Biochemical, immunological and cell genetic studies in glycogenosis type II. Am J Hum Genet 30:132–143
Ribes A, Briones P, Vilaseca MA, Lluch M, Rodes M, Maya A, Campistol J, Pascual P, Suormala T, Baumgartner R (1990) Methylmalonic aciduria with homocystimuria: biochemical studies, treatment, and clinical course of a Cbl-C patient. Eur J Pediatr 149:412–415
Rosenblatt DS, Cooper BA (1987) Inherited disorders of vitamin B12 metabolism. Blood Rev 1:177–182
Rosenblatt DS, Cooper BA, Pottier A, Lue-Shing H, Matiaszuk N, Grauer K (1984) Altered vitamin B12 metabolism in fibroblasts from a patient with megaloblastic anemia and homocystinuria due to a new defect in methionine biosynthesis. J Clin Invest 74:2149–2156
Rosenblatt DS, Hosack A, Matiaszuk NV (1985) Defect in vitamin B12 release from lysosomes: newly described inborn error of vitamin B12 metabolism. Science 228:1319
Tuchman M, Kelly P, Watkins D, Rosenblatt DS (1988) Vitamin B12-responsive megaloblastic anemia, homocystinuria, and transient methylmalonic acidura in CblE disease. J Pediatr 113:1052–1056
Watkins D, Rosenblatt DS (1986) Failure of lysosomal release of vitamin B12: a new complementation group causing methylmalonic aciduria (CblF). Am J Hum Genet 39:404–408
Watkins D, Rosenblatt DS (1988) Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG. J Clin Invest 81: 1690–1694
Watkins D, Rosenblatt DS (1989) Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. Am J Med Genet 34:427–434
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wijburg, F.A., Rosenblatt, D.S., Vos, G.D. et al. Clinical and biochemical observations in a patient with combined Pompe disease and cblC mutation. Eur J Pediatr 151, 127–131 (1992). https://doi.org/10.1007/BF01958957
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01958957