Guanidinoacetate methyltransferase (GAMT) deficiency in two Tunisian siblings: clinical and biochemical features.

BACKGROUND: Guanidinoacetate methyltransferase (GAMT) deficiency is a recently described disorder and few cases have been reported to date. As it is a treatable pathology, we seek to contribute to its better understanding, particularly to further elucidate its biochemical diagnosis for early treatment. METHODS: The patients, two brothers aged 13 years (P1) and 11 years (P2), have been explored for signs and symptoms suggestive of inborn errors of metabolism. The quantification of creatine (Cr), guanidinoacetate (GAA), and GAMT activity was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The two brothers presented a similar clinical picture: developmental delay, epilepsy, axial hypotonia, spastic tetraparesis, severe mental and language delay, and autistic behaviour. GAA concentrations were markedly increased in plasma and in urine [2796 and 3342 micromol/mmol creatinine (control range: 4 - 220 micromol/mmol creatinine)/14 and 29 micromol/L (control range: 0.35 - 1.8 micromol/L), respectively] while plasma and urine creatine concentrations were at the lower normal range limit. Activity of GAMT in lymphoblasts was extremely reduced (< 0.01 nmol/mg protein/hour) compared to healthy subjects. GAMT activity was found to be intermediary in patients' parents. CONCLUSIONS: It appears that the clinical picture is heterogeneous but should be considered as potential signs of creatine metabolism disorders, however, the biochemical diagnosis is reliable as the enzyme activity is zero in most cases. To date, it is still too early to establish correlations between symptoms and biochemical profile. However, the identification of additional cases of GAMT deficiency should help elucidate such relationships and the progress of patients treated with creatine in conjunction with ornithine supplementation.

Vitamin A, E, B12, and folic acid in end-stage renal disease Tunisian patients: status and predictive value for overall mortality and cardiovascular events.

BACKGROUND: Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed at assessing vitamin A, E, B12, and folic acid status in Tunisian ESRD patients and testing their predictive value for overall mortality and cardiovascular events (CVE). METHODS: We examined plasma vitamin A, E, B12, and folic acid in 115 ESRD patients and looked for any correlation with all-cause mortality and CVE after a six year follow-up. Vitamin A and E were determined by HPLC and vitamin B12 and folic acid were determined by enzyme immunoassay. RESULTS: At enrolment, plasma vitamin A was higher in patients than controls, while plasma vitamin B12 was higher in HD patients. No significant differences were observed for plasma vitamin E and folic acid concentrations between patients and controls. Folic acid and vitamin B12 levels were higher in supplemented patients. During the follow-up period, 17 patients were lost, 15 died, and 36 presented a CVE. Survival analysis showed that mortality and/or CVE trend to be lower for high folic acid levels (Log Rank = 0.098). Cox's regression analysis showed that high levels of folic acid are inversely related to all-cause mortality and/or CVE [Hazard ratio (95% confidence interval), 0.255 (0.08 - 0.740); p = 0.012]. CONCLUSIONS: Plasma vitamins A, E, B12, and folic acid concentrations are usually normal in Tunisian ESRD patients. High folic acid levels are associated with fewer CVE and better survival. However, as uremia could be associated with functional vitamin deficiency, maintaining high plasma vitamin levels by adequate nutrition and tolerable supplementation would be beneficial in ESRD patients.