Background: Previous studies examining reproductive parameters in men with galactosemia have inconsistently demonstrated abnormalities. We hypothesized that men with galactosemia would demonstrate evidence of reproductive dysfunction. Methods: Pubertal history, physical examination, hormone levels and semen analyses were assessed in 26 galactosemic men and compared to those in 46 controls. Results: The prevalence of cryptorchidism was higher in men with galactosemia than in the general population [9.1% vs. 1.0% (95%CI: 0.75-1.26; p=0.007)]. Testosterone (461±125 vs. 532±133 ng%; p=0.04), inhibin B (144±66 vs. 183±52 pg/mL; p=0.002) and semen concentration (46±36 vs. 112±75 x10^6 spermatozoa/mL; p=0.01) were lower and SHBG was higher (40.7±21.5 vs 26.7±14.6; p=0.002) in galactosemic men compared to controls. Semen volume was lower than normal in 7 out of 12 patients. Conclusions: Despite the limited sample size, this is the second time that a higher than expected prevalence of cryptorchidism is reported in men with classic galactosemia. The subtle decrease in testosterone and inhibin B levels and sperm count may mark mild defects in Sertoli and Leydig cell function. Follow-up studies are needed to determine the clinical consequences of these abnormalities. The low semen volumes may be an indicator of pathophysiological abnormalities in this disease and deserve further study. Background: Most female classic galactosemia patients suffer from ovarian insufficiency from an early age on. We characterized the phenotype of female galactosemia patients at different ages by MRI and/or abdominal or transvaginal ultrasound Patients and methods: 23 patients were included. MRI data of 14 patients were compared to different control patients (prepubertal, age-matched and postmenopausal) who underwent MRI for other reasons. Data on 17 ultrasounds were obtained retrospectively. Results: When comparing the ovarian volumes on MRI, the ovaries of the galactosemic girls were significantly smaller than those of the age matched controls (p=0.001) and the prepubertal ovaries (p=0.008), but did not differ significantly from postmenopausal ovarian volumes (p=0.161). Also, evidence for follicle activity was regularly seen in both the prepubertal and age matched control groups, but only rarely in the galactosemia patients and postmenopausal controls. On ultrasound, the ovaries were detected only occasionally. Conclusions: Imaging results point to early onset of ovarian abnormalities in female galactosemia patients. Little evidence for maturation of follicles was seen. Combined with the significantly smaller volumes of the ovaries we found no support for a maturation arrest alone as the main pathophysiological mechanism. This study supports the mechanism of increased follicle loss in these patients. Objectives: To define the prevalence and characteristics of motor complications in adult patients with galactosemia. Background: Early restriction of galactose prevents the neonatal complications of galactosemia, but long term problems, such as premature ovarian failure and neuropsychiatric disorders, often involving motor function, continue to develop. Their exact prevalence and phenotype are not well defined. Methods: All patients with classical galactosemia attending the Charles Dent Adult Metabolic Unit (London) from September 2010 to April 2011 were examined by a neurologist and their medical records reviewed. Results: 42 patients were examined. 26 patients (62%) had motor complications. This group also had a higher prevalence of other neurologic problems (65% vs 12%). 13 patients had symptoms related to their movement disorders and 8 reported progressive worsening. The remaining 13 had convincing signs on examination. The most common motor manifestation was tremor (N=21; 81%), followed by dystonia (N=14; 54%) and cerebellar signs (N=7; 27%). Several patients responded to standard treatments for tremor and dystonia. Conclusions: A high proportion of patients have central nervous system damage despite adhering to a galactose-restricted diet. Many develop symptomatic motor complications, mainly tremor, dystonia and cerebellar ataxia, which may progress, leading to disability and suggesting ongoing neurodegeneration. Classic galactosemia is an inborn error of galactose metabolism. Language production problems are among the most burdensome complications. This study hypothesized that galactosemia patients have language difficulties at the level of syntax (i.e. where grammatical information is retrieved and a sentence is constructed). Electroencephalography (EEG) was recorded in a group of galactosemia patients (n=22,mean age=14.9) and healthy controls (n=21,mean age=14.3), during task performance. The participants were instructed to either passively watch an animated visual scene or to utter an overt response describing this scene, requiring either minimal (separate words) or maximal syntax (sentence). Event-related-potentials (ERPs) were extracted from the continuous EEG, reflecting the brain's preparatory response to this task. Results indicate that the galactosemia ERPs start to diverge as early as 120 ms after scene presentation (P1). Also, the patient data deviates in the P2 and P6 ERP time windows (i.e. around 200 ms and 400-600 ms post-stimulus, respectively). Behaviourally, the patients need more time to prepare the utterance and make more mistakes. We suggest that galactosemia patients have not (only) late articulatory problems, but also impairments of early conceptualisation (P1), lexical access of the words (P2) and syntactic processing (P6), resulting in delays and more troublesome language production. Classical galactosaemia is an autosomal recessive inborn error of carbohydrate metabolism caused by mutations in the galactose-1phosphate uridyl tranferase gene (GALT). The objective of the present study was to investigate galactosaemia in Cyprus at the epidemiological, biochemical and molecular level. We identified two mutations in Cypriot patients with classical galactosaemia: A novel large deletion of 8489 bp encompassing all exons of the GALT gene, and the p.Lys285Asn mutation. Microsattelite analysis revealed the presence of a common haplotype suggesting a founder effect for this deletion in Cyprus. The frequency of galactosaemia carriers in the general population was estimated at 1/105 by means of GALT activity measurement in red blood cells. Molecular analysis of all carriers identified biochemically revealed three additional mutations, on one allele each: the p.Pro185Ser and the c.