Neuropediatrics 2013; 44 - PS19_1216
DOI: 10.1055/s-0033-1337845

Clinical symptoms of six children with thiamin pyrophosphokinase deficiency

J Koch 1, JA Mayr 1, T Scheffner 2, C Makowski 3, F Zimmermann 1, E Maier 1, O Debus 4, T Marquardt 4, K Schlachter 5, HC Schneider 2, H Prokisch 6, W Sperl 1, P Freisinger 2
  • 1Universitätskinderklinik, Salzburg, Austria
  • 2Klinik für Kinder- und Jugendmedizin, Kreiskliniken Reutlingen GmbH, Reutlingen, Germany
  • 3Kinderklinik München-Schwabing, Kinderklinik der Technischen Universität München, München, Germany
  • 4Klinik für Kinder- und Jugendmedizin, Akademisches Lehrkrankenhaus, Münster, Germany
  • 5Kinder- und Jugendheilkunde, Landeskrankenhaus Bregenz, Bregenz, Austria
  • 6Institut für Humangenetik, Neuherberg, Germany

Aims: Thiamin (vitamin B1) is transported into the cell and then phosphorylated to thiamin pyrophosphate (TPP) by thiamin pyrophosphokinase (TPK). TPP is an essential cofactor of five enzymes, such as pyruvate dehydrogenase. The object is to show main symptoms of patients with TPK deficiency.

Methods: Retrospective analysis of six patients with mutations in the TPK1 gene.

Results: 2/6 patients showed a primarily delayed psychomotor development, 4/6 became symptomatic at age 2 to 4 years, and 3/6 triggered by infections. The main symptom in all patients was a severe movement disorder with loss of gait, spasticity in three, dystonia in three and ataxia. Lactate in plasma and CSF was normal or slightly elevated, in 5/5 patients, α ketoglutaric acid was intermittently elevated in urine. TPP was significantly reduced in blood and muscle. Cerebral MRI at age 1 to 5 years showed an increased T2 signal intensity in the basal ganglia only in 1/5 patients. At age 10 years, there was a global atrophy with increased signal intensity in the basal ganglia in one patient. One patient suffered an acute encephalopathic crisis at age 10 years, his MRI showed a Leigh like pattern with increased T2 signaling in brain stem and cerebellum. Mild hypertrophic CMP was found in 1/5 at age 10 years. Two patients died during acute crises, triggered by infections. Patients are treated with thiamin (100 to 300 mg). The clinical course is complicate in three patients with a severe spastic dystonic movement disorder. The patient with the encephalopathic crisis recovered completely except for dysphonia, he is currently studying at university.

Conclusion: Acquired, particularly dystonic movement disorders in infancy and childhood can be caused by TPK deficiency. Symptoms can be triggered by febrile infections. Detection of α ketoglutaric acid in urine and slightly elevated lactate can be biochemical signs. Further diagnostics are testing for TPP in blood and mutation analysis. A treatment possibility is substitution with thiamin.