Summary
Morphological changes are shown in the muscle biopsy specimens of an 8-year-old girl who suffered from a triosephosphate isomerase (TPI) deficiency, resulting in a chronic, nonspherocytic, hemolytic anemia, mental retardation and neuromuscular impairment. The newly introduced enzyme histochemical reaction for TPI demonstrated a total lack of histochemically detectable enzyme activity, whereas biochemical analysis of muscle tissue revealed less than 10% of the normal enzyme activity. Electron microscopy showed a degenerative myopathy with an increase in the amount of intracellular glycogen. Additionally, mitochondrial changes within the muscle fibers were observed to be similar to those in mitochondrial myopathies. The disturbed balance between glycerinaldehyde phosphate and dihydroxy-acetone phosphate, due to the deficiency of the TPI enzyme, is interpreted as the biochemical background of an impaired electron transport across the mitochondrial membrane, resulting in the coexistence of an impaired glycolytic pathway and an impaired mitochondrial metabolism of muscle cells.
Similar content being viewed by others
References
Bardosi A, Eber SW, Roessmann U (1985) Ultrastructural and histochemical abnormalities of skeletal muscle in a patient with a new variant (type Homburg) of glucosephosphate isomerase (GPI) deficiency. Clin Neuropathol 4:72–76
Bardosi A, Creuizfeldt W, DiMauro S, Felgenhauer K, Friede RL, Goebel HH, Kohlschütter A, Mayer G, Rahlf G, Servidei S, Van Lessen G, Wetterling T (1987) Myoneuro-, gastrointestinal encephalopathy (MNGIE syndrome) due to partial deficiency of cytochrome c oxidase. A new mitochondrial multisystem disorder. Acta Neuropathol (Berl) 74:248–258
Bücher T, Luh W, Pette D (1964) Einfache und zusammengesetzte optische Tests mit Pyridinnucleotiden. In: Hoppe-Seyler F, Thierfelder H (eds) Handbuch der physiologisch-chemischen und pathologisch-chemischen Analyse, vol 6. Springer, Berlin, pp 292–339
Clark ACL, Szobolotzky MA (1986) Triose phosphate isomerase deficiency: report of a family. Aust Paediatr J 22:135–137
Clay SA, Shore NA, Landing BH (1982) Triosephosphate isomerase deficiency. A case report with neuropathological findings. Am J Dis Child 139:800–802
DiMauro S, Miranda AKF, Khan S, Gitlin K, Friedman R 1981 Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy. Science 212:1277–1279
DiMauro S, Dalakas M, Miranda AF (1983) Phosphoglycerate kinase deficiency: another cause of recurrent myoglobinuria. Ann Neurol 13:11–19
Dubowitz V (1985) Muscle biopsy. A practical approach. Baillière Tindall, London
Eber SW, Krietsch WKG (1980) The isolation and characterization of the multiple forms of human skeletal muscle triosephosphate isomerase. Biochim Biophys Acta 614:173–184
Eber SW, Pekrun A, Bardosi A, Krietsch WKG, Matthei R, Stephani U, Schröder W (1989) Triosephosphate isomerase deficiency syndrome: haemolytic anaemia, degenerative mitochondrial myopathy and mental retardation due to a new variant with accelerated enzyme aging and diminished specific activity. Eur J Paediatr (in press)
Estabrook RW, Sacktor B (1958) α-Glycerophosphate oxidase of flight muscle mitochondria. J Biol Chem 223:1014–1019
Kanno T, Sudo K, Takeucho I, Kanda S, Honda N, Nishimura Y, Oyama K (1980) Hereditary deficiency of lactate dehydrogenase M-subunit. Clin Chim Acta 108:267–276
Krebs HA (1967) Mitochondrial generation of reducing power. In: Slater EC, Kaniuga Z, Wojtczek L (eds) Biochemistry of mitochondria. Academic press, London New York, pp 105–112
Krietsch WKG, Krietsch H, Kaiser W, Dünnwald M, Kunze GWK, Duhm I, Bücker T (1977) Hereditary deficiency of phosphoglycerate kinase: a new variant in erythrocytes and leucocytes not associated with haemolytic anaemia. Eur J Clin Invest 7:427–435
Morgan-Hughes JA (1986) The mitochondrial myopathies. In: Engel AG, Banker BQ (eds) Myology vol 2. McGraw-Hill, New York, pp 1709–1743
Rapaport SM (1975) Medizinische Biochemie. VEB Verlag, Volk und Gesundheit, Berlin, pp 250–251
Schneider AS, Valentine WM, Hattori M, Heins HL (1965) Hereditary hemolytic anemia with triosephosphate isomerase deficiency. N Engl J Med 272:229–235
Schneider AS, Dunn I, Ibsen KH, Weinstein IM (1968) Triosephosphate isomerase deficiency. B. Inherited triosephosphate isomerase deficiency. Erythrocyte carbohydrate metabolism and preliminary studies of erythrocyte enzyme. In: Beutler E (ed) Hereditary disorders of erythrocyte metabolism. Grune and Stratton, New York, pp 273–279
Schröter W, Eber SW, Bardosi A, Gahr M, Gabriel M, Sitzmann FC (1985) Generalized glucosephosphate isomerase (GPI) deficiency causing haemolytic anaemia, neuromuscular symptoms and impairment of granulocytic function: a new syndrome due to a new stable GPI variant with dimished specific activity (GPI Homburg). Eur J Pediatr 144:301–305
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bardosi, A., Eber, S.W., Hendrys, M. et al. Myopathy with altered mitochondria due to a triosephosphate isomerase (TPI) deficiency. Acta Neuropathol 79, 387–394 (1990). https://doi.org/10.1007/BF00308714
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00308714