Promising treatment in a boy with creatine transporter deficiency

The X chromosomal defect of creatine transport is a rare disease affecting boys. Clinical presentation is unspecific with developmental delay, retarded speech development and autistic behavior. The lack of the short time energy supplying molecule creatinephosphat disturbs brain development. Current therapeutic strategies focus on stimulation of local synthesis by increasing the availability of the metabolic precursor's agrinine and gycine. Case: We report about a now 4 year old German boy of healthy parents, who presented with delay in developmental mile stones, focusing on speech delay and autistic, hyperactive behavior. Mile stones: walking 20 month, no Speech until 3 years. Physical examination at age of 2 years showed slightly decreased muscle tone. EEG was normal. Cranial MRI showed hyper intensity in T2 and FLAIR bilateral in tegmentum pontis and peritrigonal. MR-Spectroscopy revealed a lack of ceratine/phosphocreatine (C/PC) in the brain. Urinary excretion of creatine was increased in two specimens but normal in two others. Molecular genetic testing of the SLC6A8 gene revealed a stop codon at position 566 of the X chromosomal, also hemizygote in the mother. Therapy was started creatine 400mg/kg, arginine 400mg/kg and glycine 400mg/kg at the age of 3 years 6 month. In the following 7 month the parents noticed positive changes and reported of increasing attention, decreasing of hyperactivity and success in speech development resulting in the first spoken words with 4 years. MRS showed a slight increase in C/PC under therapy. There were no side effects. Discussion: Creatine transporter deficiency is a rare disease, but seems to be under diagnosed, because of its unspecific clinical presentation. MRS is no routine diagnostic method and urinary excretion, as reported, is uncertain, because of the influence of dietary intake of creatine. MRI in our patient revealed lesions in the brain stem not been reported before. Treatment with arginine was reported by Fons at al. in adolescent patients having no effect and by Chilosi at al. with positive effects on behavior. The basic mechanism of disease seems to influence negatively brain development especially in first years of live, which cannot be recovered later. The early diagnosis and treatment therefore seems to have equal effects as seen in other metabolic disease like PKU or hypothyroidism.