[MIM 615 512]

(TPI deficiency)

Prevalence is unknown: less than 50 reported cases. Autosomal recessive transmission. TPI deficiency is due to mutations of the gene coding for the triosephosphate isomerase (TPI1, on 12p13.31). The frequency of heterozygosity is estimated at 0,4-1% in Europe and Asia, and 4% in African Americans: this suggests that the homozygosity is often lethal in utero. Severe abnormality of glycolytic metabolism characterized by hemolytic anemia and neurodegeneration.

-        hemolytic anemia: jaundice, reticulocytosis, and hyperbilirubinemia are common. Patients often have bacterial infections of the respiratory system.

-        in the classic form, widespread manifestations of progressive neurological degeneration appear around 6 to 24 months of age  with dystonia, tremor, dyskinesia, pyramidal signs, cardiomyopathy and damage of motor neurons with progressive neuromuscular deterioration. Cognitive function is little influenced and developmental retardation is mostly related to the motor deficit affecting mobility and speech.

-        chronic axonal neuropathy has been shown on biopsies and EMG.

-        sometimes, a severe microcephalic convulsive encephalopathy.

Diagnosis: deficit of the enzymatic activity (2-30% of normal values) and  accumulation of the toxic substrate phosphate dehydrogenase (DHAP) in the erythrocytes (concentration 15 to 100 times above normal). Muscle biopsy shows myopathic changes.
Treatment: blood transfusions and management for a progressive neuromuscular disease.
The prognosis is poor, especially for homozygous patients with a mutation in Glu104Asp or heterozygous  patients with an allele inefficient for the triosephosphate isomerase and the Glu104Asp. For these cases, life expectancy is usually reduced to infancy or early childhood, while patients with other mutations have a longer survival expectancy. The first cause of death is respiratory failure and infections.

Anesthetic implications:

check the hemoglobin level, lung function, ECG and cardiac ultrasound. Metabolic myopathy: avoid succinylcholine and the use of a surgical tourniquet.

References : 

Updated: September 2016