Creatine transporter deficiency: Novel mutations and functional studies.

X-linked cerebral creatine deficiency (MIM 300036) is caused by deficiency of the creatine transporter encoded by the SLC6A8 gene. Here we report three patients with this condition from Israel. These unrelated patients were evaluated for global developmental delays and language apraxia. Borderline microcephaly was noted in one of them. Diagnosis was prompted by brain magnetic resonance imaging and spectroscopy which revealed normal white matter distribution, but absence of the creatine peak in all three patients. Biochemical testing indicated normal plasma levels of creatine and guanidinoacetate, but an increased urine creatine/creatinine ratio. The diagnosis was confirmed by demonstrating absent ([14])C-creatine transport in fibroblasts. Molecular studies indicated that the first patient is hemizygous for a single nucleotide change substituting a single amino acid (c.619 C > T, p.R207W). Expression studies in HeLa cells confirmed the causative role of the R207W substitution. The second patient had a three base pair deletion in the SLC6A8 gene (c.1222_1224delTTC, p.F408del) as well as a single base change (c.1254 + 1G > A) at a splicing site in the intron-exon junction of exon 8, the latter occurring de novo. The third patient, had a three base pair deletion (c.1006_1008delAAC, p.N336del) previously reported in other patients with creatine transporter deficiency. These three patients are the first reported cases of creatine transporter deficiency in Israel.

Prediction of participation and sensory modulation of late preterm infants at 12 months: a prospective study.

The aim of the study was to prospectively assess the differences in participation and sensory modulation between late preterm infants (LPI) and term babies, and to predict it by LPI characteristics. The study population includes 124 late preterm infants at gestational age between 34 and 35 6/7 weeks who were born at the same medical center. The control group comprised of 33 term babies (18 boys, 15 girls), born during the same period and location (mean age 12.47, SD = 0.73). Sensory modulation was assessed by the test of sensory functions in infants and the infant/toddler sensory profile and for assessment of participation and parents' satisfaction we used questionnaires. Term infants had better sensory modulation than LPI. Approximately 10% of the sensory modulation of participants in the study was explained by gestational age and head circumference. LPI participation and parental satisfaction decreased in the LPI group. Among all the explanatory variables only multiple gestations and head circumference contributed to the explained variance of participation (16%), and parents' satisfaction (13%). At age of 1 year, children born as late preterm are at increased risk of developing sensory modulation disorder, showing less participation, and resulting in less parental satisfaction.