Phosphomannomutase 2 (PMM2-CDG) is the most common congenital disorder of N-glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2-CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach. In this article, a systematic review of the literature on PMM2-CDG was conducted by a group of international experts in different aspects of CDG. Our managment guidelines were initiated based on the available evidence-based data and experts' opinions. This guideline mainly addresses the clinical evaluation of each system/organ involved in PMM2-CDG, and the recommended management approach. It is the first systematic review of current practices in PMM2-CDG and the first guidelines aiming at establishing a practical approach to the recognition, diagnosis and management of PMM2-CDG patients.

In this study, percentage contributions of arachidonic and docosahexaenoic acids as well as the those of the intermediary metabolites of essential fatty acid metabolism were all significantly higher in early human milk samples of mothers giving birth to very low birth weight preterm as compared with full-term infants.

The present study was carried out to investigate leptin levels in arterial and venous cord serum and in amniotic fluid in full-term infants at birth and on the 5th postnatal day to define the relationship of leptin to intrauterine growth rate, gender and early postnatal life. The relation of weight gain to serum leptin levels in male preterm infants was determined measuring leptin concentration weekly in the first 5 postnatal weeks. Testosterone levels were determined simultaneously to explore a possible relationship between leptin and testosterone concentrations.Fifty-three term newborn infants with mean birth weight and gestational age of 3,419 g (range 2,150–4,480) and 38.9 weeks (range 36–41) and 19 preterm male infants (mean birth weight and gestational age were 1,416 g (770–1,800) and 30.2 weeks (26–35) were enrolled into the study. Leptin and testosterone levels were determined by radioimmunoassay. It was demonstrated that serum leptin levels were markedly elevated in the cord blood without discernible arteriovenous differences. Cord blood leptin was found to correlate with birth weight (r = 0.40, p < 0.002), weight to length ratio (r = 0.40, p < 0.002) and body mass index (r = 0.35, p < 0.005). It was significantly lower in boys as opposed to girls (p < 0.01) and there was an apparent fall by the 5th postnatal day (p < 0.001). Amniotic fluid contained leptin in much less concentration than cord blood and it proved to be independent of intrauterine growth or gender. Serum leptin concentration in preterm infants at 1 week of age was significantly lower compared with term infants (p < 0.002) and it increased progressively with age (p < 0.01). An inverse relationship was found between leptin and testosterone level (r = –0.358, p < 0.01) and a positive correlation between leptin level and weight/height ratio (r = 0.674, p < 0.01).It is concluded that leptin derived either from placenta or fetal adipose tissue may be involved in regulating fetal growth and development and it may be related to energy intake, storage and expenditure. In preterm male infants serum leptin concentration increases with postnatal weight and testosterone may suppress leptin synthesis.

Congenital disorders of glycosylation (CDG) are a rapidly growing family of inborn errors. Screening for CDG in suspected cases is usually performed in the first year of life by serum transferrin isoelectric focusing or mass spectrometry. Based on the transferrin analysis patients can be biochemically diagnosed with a type 1 or type 2 transferrin pattern, and labeled as CDG-I, or CDG-II. The diagnosis of CDG is frequently delayed due to the highly variable phenotype, some cases showing single organ involvement and others mimicking syndromes, like skeletal dysplasia, cutis laxa syndrome, or congenital muscle dystrophy. The aim of our study was to evaluate perinatal abnormalities and early discriminative symptoms in 58 patients consecutively diagnosed with diverse CDG-subtypes. Neonatal findings and clinical features in the first months of life were studied in 36 children with CDG-I and 22 with CDG-II. Maternal complications were found in five, small for gestational age in nine patients. Five children had abnormal neonatal screening results for hypothyroidism. Congenital microcephaly and neonatal seizures were common in CDG-II. Inverted nipples were uncommon with 5 out of 58 children. Dysmorphic features were mostly nonspecific, except for cutis laxa. Early complications included feeding problems, cardiomyopathy, thrombosis, and bleeding. Cases presenting in the neonatal period had the highest mortality rate. Survival in CDG patients is highly dependent on early intervention therapy. We recommend low threshold screening for glycosylation disorders in infants with neurologic symptoms, even in the absence of abnormal fat distribution. Growth retardation and neonatal bleeding increase suspicion for CDG.

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Most preterm infant formulas contain mediumchain triacylglycerols (MCT), but the effects of MCT on polyunsaturated fatty acid status and metabolism are controversial. Thus, we studied the effects of MCT on linoleic acid metabolism using stable isotopes. Enterally fed preterm infants were randomized to receive for 7 days 40% of fat as MCT (n ‫؍‬ 10) or a formula without MCT (n ‫؍‬ 9). At study day 5, infants received orally 2 mg/kg body weight of 13 C-labeled linoleic acid. Fatty acids in plasma lipid classes and 13 C enrichment of phospholipid fatty acids were measured and tracer oxidation was monitored. Compared with the control group, the MCT group showed lower breath 13 CO 2 and higher plasma triacylglycerol contents of octanoic acid, of decanoic acid, and of total long-chain polyunsaturated fatty acids (57.1 ؎ 4.4 mol/l vs. 37.9 ؎ 4.8 mol/l, P Ͻ 0.01). Concentrations of several polyunsaturated fatty acids in plasma phospholipids and non esterified fatty acids were higher in the MCT group. 13 C concentrations in phospholipid n-6 fatty acids indicated no difference in the relative conversion of linoleic to arachidonic acid. We conclude that oral MCT effectively reduce polyunsaturated fatty acid and long chain polyunsaturated fatty acid oxidation in preterm infants without compromising endogenous n-6 long chain polyunsaturated fatty acid synthesis.

Background: Fatty acid composition of human milk (HM) is known to change considerably during lactation. However, we were unable to find data on changes of fatty acid composition of HM during the very early phase of lactation, i.e. in the first week of life. Subjects and Methods: HM samples were obtained from 18 healthy lactating women every day during the first week and thereafter on the 14th and 28th days of lactation. Fatty acid composition of colostrum and mature HM samples was determined by high-resolution capillary gas-liquid chromatography. Results: Values of the n-6 essential fatty acid, linoleic acid, in HM did not change significantly during the first month of lactation, whereas values of the n-3 essential fatty acid, α-linolenic acid, showed significant increases during the first 2 weeks of lactation (1st day: 0.49 [0.12], % weight/weight, median [ranges from the 1st to the 3rd quartile], 14th day: 0.69 [0.31], p < 0.05). In contrast, values of the n-6 long-chain metabolites, eicosadienoic-, dihomo-γ-linolenic- and arachidonic acid, as well as the values of the n-3 long-chain metabolites, eicosatrienoic-, and eicosapentaenoic acid exhibited significant decreases during the entire period investigated. The principal n-3 long-chain metabolite, docosahexaenoic acid, showed a significant increase between the 3rd and 14th days, but a significant decrease between the 14th and 28th days (3rd day: 0.15 [0.13], 14th day: 0.28 [0.11], p < 0.05, 28th day: 0.19 [0.12], p < 0.01). There were statistically significant positive correlations between arachidonic and docosahexaenoic acid values on the 1st (r = 0.67, p < 0.01), 5th (r = 0.56, p < 0.05) and the 6th (r = 0.53, p < 0.05) days of lactation. Conclusion: Fatty acid composition of HM changes significantly even during the first week of lactation. The lack of positive correlation between essential fatty acids and their long-chain metabolites suggests that it is not only the availability of essential fatty acids that influences the fatty acid composition of human colostrum.

Bone disease might occur early in the course in autosomal recessive cutis laxa syndrome. We report on a significant clinical improvement and stabilization in our patients following bisphosphonate therapy. We suggest early, systemic evaluation and follow up of bone density in all children presenting with inherited cutis laxa.