Health  Vol.4 No.9 , September 2012
Atypical presentations of propionic acidemia
ABSTRACT
One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) which results from Propionyle-CoA Carboxylase (PCC) enzyme deficiency that is necessary for the catabolism of the branched chain Amino Acids and other metabolites. Classically this disease presented with high anion gap metabolic acidosis with its clinical consequences. We report 4 patients who presented to our facility with sepsis like picture and no metabolic acidosis. All of them were found to have high ammonia level. Diagnosis was confirmed by tandem MS/MS and urine Gas Chromatography/ Mass Spectrometry (GC/MS). All of them were treated supportively and by supplementation of adequate calories and PA formula. The different presentations may be very well attributed to the PCC molecular defects heterogeneity. Mutations in both genes PCCA and PCCB can cause PA with more frequent heterogeneity of PCCA gene. In spite of the fact that PCCB gene is responsible for the most of the oriental cases, our first patient condition was attributed to PCCA gene with a rare mutation which was not described in the literatures.

Cite this paper
Al-Asmari, A. and Al-Makadma, A. (2012) Atypical presentations of propionic acidemia. Health, 4, 629-633. doi: 10.4236/health.2012.49099.
References
[1]   Ogier, H., Charpentier, C., Saudubray, J.M. (1990) Organic acidemias. In: Fernandes, J., Saudubray, J.M., Tada, K., Eds., Inborn Metabolic Diseases, Springer-Verlag, Berlin, 271-299.

[2]   Rosenbery, L.E. and Fenton, W.A. (1989) Disorders of propionate and methylmalonate metabolism. In: Scriver, C.R., Beaudet, A.L. and Valle, D., Eds., The Metabolic Basis of Inherited Disease, 6th Edition, McGraw-Hill, New York, 821-844.

[3]   Sass, J.O., Hofmann, M., Skladal, D., Mayatepek, E., Schwahn, B. and Sperl, W. (2004) Propionic acidemia revisited: A workshop report. Clinical Pediatrics, 43, 837-843. doi:10.1177/000992280404300908

[4]   Wolf, B., Hsia, Y.E., Sweetman, L., et al. (1981) Propionic acedimia: A clinical update. Journal of Pediatrics, 99, 835-846. doi:10.1016/S0022-3476(81)80004-2

[5]   Gravel, R.A., Lam, K.F., Mahuran, D. and Kronis, A. (1980) Purification of human liver propionyl-CoA carboxylase by carbon tetrachloride extraction and monomeric avidin affinity chromatography. Archives of Biochemistry and Biophysics, 201, 669-673. doi:10.1016/0003-9861(80)90557-3

[6]   Kalousek, F., Darigo, M.D. and Rosenberg, L.E. (1980) Isolation and characterization of propionyl-CoA carboxylase from normal human liver: Evidence for a protomeric tetramer of non-identical subunits. Journal of Biological Chemistry, 255, 60-65.

[7]   Lamhonwah, A.M., Troxel, C.E., Schuster, S. and Gravel, R.A. (1990) Two distinct mutations at the same site in the PCCB gene in propionic acidemia. Genomics, 8, 249-254. doi:10.1016/0888-7543(90)90279-4

[8]   Urgarte, M., Perez-Cerda, C., Rodriquez-Pombo, P., Desviat, L.R., Perez, B., Richard, E., et al. (1999) Overview of mutations in the PCCA and PCCB genes causing propionic acidemia. Human Mutation, 14, 275-282. doi:10.1002/(SICI)1098-1004(199910)14:4<275::AID-HUMU1>3.0.CO;2-N

[9]   Ohura, T., Miyabashi, S., Narisawa, K., Tada, K. (1991) Genetic heterogeneity of propionic acidemia: Analysis of Japanese patients. Human Genetics, 87, 41-44. doi:10.1007/BF01213089

[10]   Ozand, P.T., Rashed, M., Gascon, G.G., Youssef, N.G., Harfi, H., Rahbeeni, Z., Al Garawi, S. and Al Aqeel, A. (1994) Unusual presentations of propionic acidemia. Brain and Development, 16, 46-57. doi:10.1016/0387-7604(94)90096-5

[11]   Al Essa, M., Rahbeeni, Z., Jumaah, S., Joshi, S., Al Jishi, E., Rashed, M.S., Al Amoudi, M. and Ozand, P.T. (1998) Infectious complications of propionic acidemia in Saudia Arabia. Clinical Genetics, 54, 90-94. doi:10.1111/j.1399-0004.1998.tb03702.x

[12]   Rashed, M. (2001) Clinical applications of tandem mass spectrometry: Ten years of diagnosis and screening for inherited metabolic diseases. Journal of Chromatography, 758, 27-48.

[13]   Leonard, J.V., Daish, P., Naughten, E.R. and Bartlett, K. (1984) The management and long term outcome of organic acidaemias. Journal of Inherited Metabolic Disease, 7, 13-17. doi:10.1007/BF03047367

[14]   Surtees, R.A., Matthews, E.E. and Leonard, J.V. (1992) Neurologic outcome of propionic acidemia. Pediatr Neurol, 8, 333-337. doi:10.1016/0887-8994(92)90085-D

[15]   Lucke, T., Perez-Cerda, C., Baumgartner, M., et al. (2004) Propionic acidemia: Unusual course with late onset and fatal outcome. Metabolism, 53, 809-810. doi:10.1016/j.metabol.2003.12.025

[16]   North, K.N., Korson, M.S., Gopal, Y.R., et al. (1995) Neonatal onset propionic acidemia: Neurologic and developmental profiles, and implications of management. Journal of Pediatrics, 126, 916-922.

[17]   Tokatli, A., Coskun, T. and Ozalp, I. (1993) A retrospective evaluation of 78 cases with organic acidemia. Turkish Journal of Medical Sciences, 18, 47-53.

[18]   Desviat, L.R., Pérez, B., Pérez-Cerdá, C., Rodríguez-Pombo, P., Clavero, S. and Ugarte, M. (2004) Propionic acidemia: Mutation update and functional and structural effects of the variant alleles. Molecular Genetics and Metabolism, 83, 28-37. doi:10.1016/j.ymgme.2004.08.001

 
 
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