Hereditary triosephosphate isomerase (TPI) deficiency : two severely affected brothers one with and one without neurological symptoms

• Published in: Human genetics Vol. 92; no. 5; pp. 486 - 490
• Main Authors: HOLLAN, S, FUJII, H, HIRONO, A, HIRONO, K, KARRO, K, MIWA, S, HARSANYI, V, GYODI, E, INSELT-KOVACS, M
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-11-1993; Berlin; New York, NY
• Subjects: Adult; Age of Onset; Anemia, Hemolytic, Congenital - enzymology; Anemia, Hemolytic, Congenital - genetics; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; case reports; Central Nervous System Diseases - enzymology; Central Nervous System Diseases - genetics; Child; deficiency; Dihydroxyacetone Phosphate - blood; Errors of metabolism; Erythrocytes - enzymology; Female; Heterozygote; Homozygote; Humans; Hyperkinesis - enzymology; Hyperkinesis - genetics; Male; man; Medical sciences; Metabolic diseases; Metabolism, Inborn Errors - genetics; neurology; triose-phosphate isomerase; Triose-Phosphate Isomerase - deficiency; Triose-Phosphate Isomerase - genetics; Hungary; Europe; Human; Nervous system diseases; Intramolecular oxidoreductases; Enzyme; Family study; Deficiency; Red blood cell; Metabolic diseases; Hemopathy; Enzymopathy; Triose-phosphate isomerase; Involuntary movement; Case study; Isomerases; Hemolytic anemia; Adolescent; Neurological disorder; Extrapyramidal syndrome; Dyskinesia
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/BF00216456

A 13-year-old Hungarian boy (B.J.Jr.) with congenital haemolytic anaemia (CHA) and hyperkinetic torsion dyskinesia was found to have severe triose-phosphate isomerase (TPI) deficiency. One of his two brothers (A.J.), a 23-year-old amateur wrestler, has CHA as well, but no neurological symptoms. Both have less than 10% TPI activity and a highly increased dihydroxyacetone phosphate (DHAP) level in their red blood cells. Their TPI had a slow electrophoretic mobility and was heat unstable. Both parents and a third brother are healthy heterozygous carriers of the defect. A.J. represents a unique phenotype from the point of view that all published "homozygotes" had severe neurological alterations from infancy or early childhood except one infant who died at 11 months, probably too young for neurological symptoms to be noted. In contrast to the two affected Hungarian brothers all but one "homozygote" has died before the age of 6 years. The striking difference in the clinical course of the defect between the two brothers with the same severe red blood cell enzyme deficiency may originate from unusual differences between two double heterozygous brothers resulting inter alia in different levels of TPI expression in various tissues. Significantly lower TPI activities were found in both the T- and B-cells of the propositus as compared to the respective cells of the neurologically symptom-free brother.