Clinical Presentations of Patients with Polyol Abnormalities

Abstract

Since our description of a patient with leukoencephalopathy and highly elevated polyols in the brain and body fluids, we started screening for polyol abnormalities in patients highly suspected of a metabolic disorder. We identified four additional patients with consistent abnormalities in sugar and polyol profiles in body fluids. The clinical, neuroimaging, and biochemical findings of the five patients detected so far are described in the present paper. In four patients neurological problems dominated the clinical picture, whereas liver failure dominated in the other patient. The sugar and polyol profiles were abnormal in body fluids in all patients, but the profiles were different in individual patients. A deficiency of transaldolase was found in the patient presenting with liver failure. We were not able to identify the basic defect in the four patients with predominantly neurological problems. The differences in clinical picture, MRI abnormalities, and sugar and polyol profiles in these patients suggest that the underlying defects may be different. Whether the abnormal sugar and polyol profiles are directly related to the cause of disease via defects in polyol metabolism or transport remains to be elucidated.

Key words

Metabolic disorders - neuroimaging - polyol - sugars - transaldolase

References

• 1 Alizade M A, Brendel K, Gaede K. Chirality of xylitol-oxidizing enzymes from mammalian liver.  FEBS Lett. 1976;  67 41-44
• 2 Berry G T. The role of polyols in the pathophysiology of hypergalactosemia.  Eur J Pediatr. 1995;  154 S53-S64
• 3 Berry G T, Hunter J V, Wang Z, Dreha S, Mazur A, Brooks D G. et al . In vivo evidence of brain galactitol accumulation in an infant with galactosemia and encephalopathy.  J Pediatr. 2001;  138 260-262
• 4 Gabbay K H. Hyperglycemia, polyol metabolism, and complications of diabetes mellitus.  Annu Rev Med. 1975;  26 521-536
• 5 Gibson K M, Lee C F, Chambliss K L, Kamali V, Francois B, Jaeken J. et al . 4-Hydroxybutyric aciduria: application of a fluorometric assay to the determination of succinic semialdehyde dehydrogenase activity in extracts of cultured human lymphoblasts.  Clin Chim Acta. 1991;  196 219-221
• 6 Hickman J, Ashwell G. A sensitive and stereospecific enzymatic assay for xylulose.  J Biol Chem. 1959;  234 758-761
• 7 Jakoby W B, Fredericks J. Erythritol dehydrogenase from Aerobacter aerogenes.  Biochim Biophys Acta. 1961;  48 26-32
• 8 Jansen G, Muskiet F A, Schierbeek H, Berger R, van der Slik S W. Capillary gas chromatographic profiling of urinary, plasma and erythrocyte sugars and polyols as their trimethylsilyl derivatives, preceded by a simple and rapid prepurification method.  Clin Chim Acta. 1986;  157 277-293
• 9 Kusmierz J, DeGeorge J J, Sweeney D, May C, Rapoport S I. Quantitative analysis of polyols in human plasma and cerebrospinal fluid.  J Chromatogr. 1989;  497 39-48
• 10 Makinen K K. Effect of long-term, peroral administration of sugar alcohols on man.  Swed Dent J. 1984;  8 113-124
• 11 Onkenhout W, Groener J E, Verhoeven N M, Yin C, Laan L A. l-Arabinosuria: a new defect in human pentose metabolism.  Mol Genet Metab. 2002;  77 80-85
• 12 Santer R, Schneppenheim R, Dombrowski A, Gotze H, Steinmann B, Schaub J. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome.  Nat Genet. 1997;  17 324-326
• 13 Shetty H U, Holloway H W, Rapoport S I. Capillary gas chromatography combined with ion trap detection for quantitative profiling of polyols in cerebrospinal fluid and plasma.  Anal Biochem. 1995;  224 279-285
• 14 Touster O, Shaw D. Biochemistry of the acyclic polyols.  Physiol Rev. 1962;  42 181-225
• 15 van der Knaap M S, Wevers R A, Struys E A, Verhoeven N M, Pouwels P J, Engelke U F. et al . Leukoencephalopathy associated with a disturbance in the metabolism of polyols.  Ann Neurol. 1999;  46 925-928
• 16 Verhoeven N M, Huck J HJ, Roos B, Struys E A, Salomons G S, Douwes A C. et al . Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway.  Am J Hum Genet. 2001;  68 1086-1092
• 17 Weidinger S, Cleve H, Schwarzfischer F, Postel W, Weser J, Gorg A. Transferrin subtypes and variants in Germany; further evidence for a Tf null allele.  Hum Genet. 1984;  66 356-360