Dilated cardiomyopathy in mucolipidosis type 2.

Mucolipidosis II and III are lysosomal storage diseases caused by pathogenetic mutations in GNPTAB and GNPTG genes which cause an impaired activity of the lysosomal hydrolase N-acetylglucosamine- 1-phosphotransferase, a key enzyme in the synthesis of the mannose-6-phosphate targeting signals on lysosomal enzymes. Patients with MLII alpha/beta present coarse facial features, cessation of statural growth, important skeletal manifestations, impaired neuromotor development and cardiorespiratory involvement. All children appear to have cardiac involvement, but severe dilated cardiomyopathy is uncommon. In this report we describe the case of an 11-month-old girl who is affected by a MLII. Analysis of the GNPTAB gene identified at a heterozygous level the previously described gene variants c. 2693delA p(Lys898Serfs*13) and c. 2956C>T p(Arg986Cys). Her main clinical features were coarse face with gingival hypertrophy, dysostosis multiplex, recurrent respiratory infection and an early onset of dilated cardiomyopathy, an uncommon feature for MLII. To our knowledge, dilated cardiomyopathy has been previously described in literature in only two cases of MLII and in one patient affected by MLIII.

Mental retardation in mucopolysaccharidoses correlates with high molecular weight urinary heparan sulphate derived glucosamine.

Mucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.

Joint attention behaviours and vocabulary development in children with Down syndrome.

BACKGROUND: Because of their difficulties in language development, various studies have focussed on the precursors of linguistic skills in children with Down syndrome. However, data on the predictive role of joint attention on language development in this population are inconsistent. The present study aimed to analyse attention behaviours in a group of children with Down syndrome. The existence of both concurrent and longitudinal relationships between joint attention and vocabulary development was investigated. METHOD: The participants were 18, 24-month-old, Italian children with Down syndrome. The children's attention skills were assessed during semi-structured free-play sessions in interaction with their mothers. A nominal exhaustive scheme was applied to code the children's behaviour. Moreover, the children's vocabulary development (both receptive and expressive) was assessed with the Italian version of the MacArthur-Bates Communicative Development Inventory at both 24 and 30 months. RESULTS: Data analyses showed that children with Down syndrome spent a large part of the interactive play session in joint attention situations. Moreover, the children's behaviour of proposing a joint attention focus to their communicative partners appeared to be a significant predictor of the children's vocabulary comprehension skills as assessed 6 months later. CONCLUSIONS: These results support the hypothesis of continuity between preverbal precursors and vocabulary development in a population with atypical development.

Effects of Holder pasteurization on human milk oligosaccharides.

The benefits of human milk have been confirmed for preterm infants, due to its nutritional aspects and to its biologically active compounds. Oligosaccharides play an emerging leading role among these compounds. Mother's milk can sometimes be lacking for preterm infants; pasteurized donor milk represents therefore an important alternative. The aim of this study is to evaluate the effects of Holder pasteurization on the concentration and pattern of oligosaccharides in preterm human milk. Our results indicate that pasteurization does not affect the concentration or pattern of analyzed oligosaccharides.

Prebiotics in human milk: a review.

The microbic colonization of human intestine begins at birth, when from a sterile state the newborn is exposed to an external environment rich in various bacterial species. The kind of delivery has an important influence on the composition of the intestinal flora in the first days of life. Thereafter, the microflora is mainly influenced by the kind of feeding: breast-fed infants show a predominance of bifidobacteria and lactobacilli, whereas bottle-fed infants develop a mixed flora with a lower number of bifidobacteria. The "bifidogenic effect" of human milk is not related to a single growth-promoting substance, but rather to a complex of interacting factors. In particular the prebiotic effect has been ascribed to the low concentration of proteins and phosphates, the presence of lactoferrin, lactose, nucleotides and oligosaccharides. The real prebiotic role of each of these substances is not yet clearly defined, with the exception of oligosaccharides which undoubtedly promote a bifidobacteria-dominant microflora.

Prebiotics in infant formulas: biochemical characterisation by thin layer chromatography and high performance anion exchange chromatography.

BACKGROUND: Breast-fed infants, unlike bottle-fed babies, have a microbic intestinal flora characterised by a marked predominance of bifidobacteria and lactic acid bacteria. This is essentially due to the prebiotic effect of oligosaccharides in human milk. Recently, oligosaccharides with a prebiotic effect have been added to formulas. Aim. To characterise the mixture of oligosaccharides contained in these new formulas. MATERIALS AND METHODS: The characterisation of oligosaccharides was performed using thin layer chromatography as well as high performance anion exchange chromatography. RESULTS: The mixture of oligosaccharides used in the formulas analysed was made up of oligosaccharides with low molecular weight (transgalactosylated oligosaccharides) and polysaccharides with high molecular weight (inulin). CONCLUSION: With the methods employed, it was possible to characterise the mixture of oligosaccharides used as prebiotics in the formulas now available on the market.

Characterization of oligosaccharides in milk and feces of breast-fed infants by high-performance anion-exchange chromatography.

Human milk contains a large amount of oligosaccharides, which represent its third largest solute. Nevertheless, both the metabolism and the role of these substances are still largely unknown. A previous study we conducted documented that the amount of oligosaccharides excreted in the feces varies from 6% to 13% of the 24-hour ingested oligosaccharides. The aim of this study was to characterize the pattern of oligosaccharides in the feces compared with the pattern of the ingested milk. Six term newborn infants were studied at the end of the first month of life. A 7:00 AM milk sample was obtained with an electric breast pump. Feces were collected during the day of milk sampling. Analyses of oligosaccharides were performed using high-pH anion-exchange chromatography with pulsed amperometer detection. Pure milk oligosaccharides were used as reference standards. The chromatographic profile of the oligosaccharides present in the feces and in the milk samples showed more than 40 peaks, 20 of which have been identified. The oligosaccharide profile observed in the feces was similar to the pattern of oligosaccharides present in the milk ingested. A significant difference was represented by the almost complete absence of lactose in the feces of all infants and of sialyllacto-N-tetraose a and disialyllacto-N-neotetraose in 3 samples. A substantial reduction of lacto-N-tetraose was observed in 5 samples. Our results demonstrate that the oligosaccharide profile in the feces is similar to that of the ingested milk. Approximately 40% to 50% of the total ingested oligosaccharides can be found in feces of breast-fed infants.

Oligosaccharides in human milk during different phases of lactation.

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l(-1)) and then decreases by about 20% at day 30 of lactation. The protective role played by these substances against different infectious agents, in different organs and systems of the breastfed baby, is emphasized.

Lactose, oligosaccharide and monosaccharide content of milk from mothers delivering preterm newborns over the first month of lactation.

BACKGROUND: Monosaccharide, lactose and oligosaccharide content of milk from mothers delivering prematurely (PT milk) was studied to evaluate whether changes occur during lactation, as observed in milk from mothers delivering at term (T milk). METHODS: To study a homogeneous population, women having the most common phenotype (secretory both Lewis and A, B, or H phenotype) were selected. Milk samples from 26 mothers who delivered between the 27th and 35th week of gestation were collected at the 4th, 10th, and 30th post-partum days. Monosaccharides, lactose and oligosaccharides were measured by high-pressure liquid chromatography. RESULTS: Lactose concentration increased significantly (p < 0.05) from 52.81 +/- 8.2 g/L on day 4 to 69.24 +/- 9.36 g/L on day 30. During the same period of time oligosaccharide content decreased significantly (p < 0.05) from 25.61 +/- 5.19 g/L to 15.83 +/- 6.05 g/L. Monosaccharides did not show statistically significant variations. CONCLUSIONS: Our results indicate that PT milk contains in addition to lactose, a substantial amount of oligosaccharides and a lower percentage of monosaccharides. Compared to T milk, in the colostral phase PT milk presents significantly lower lactose concentration (p < 0.0001); on the contrary its oligosaccharide content is significantly higher (p < 0.0001). The physiological role of human milk carbohydrates in view of the peculiar needs of the preterm newborn is also discussed.

Bone marrow transplantation in Hunter syndrome (mucopolysaccharidosis type II): two-year follow-up of the first Italian patient and review of the literature.

A patient with Hunter syndrome, or mucopolysaccharidosis type II (MPS-osis II), was subjected to bone marrow transplantation (BMT), at the age of 2 9/12 years. A two-year follow-up ensued to the purpose of comparing clinical, biochemical, neuropsychologic status pre- and post-BMT. From the clinical standpoint, a complete normalization of hepatosplenomegaly was observed. In addition the skin decreased in thickness and joint mobility improved. The echocardiography showed normalization of left ventricle size. With the exception of verbal capabilities, there was no further deterioration of the neuropsychologic profile. The ultrastructural examination of the liver showed an almost total disappearance of storage material. Normal iduronate sulfatase levels in leukocytes and lymphoblasts were constantly found after BMT. A qualitative and quantitative improvement in urinary glycosaminoglycan (GAG) excretion was also found. The effectiveness of the BMT in our patient is also assessed in the context of the few cases of MPS-osis II that have been reported to date. A final evaluation of the efficacy of BMT in MPS-osis II will be possible only when a higher number of patients, diagnosed as early as possible and transplanted within the first months of life, can be followed-up for more extended periods of time.

[Sex behavior and sexually transmitted diseases in drug-dependent women: study of 465 cases]. / Comportamento sessuale e malattie sessualmente trasmesse nelle donne tossicodipendenti: studio su 465 casi.

465 intravenous drug abuser (IVDA) women were studied to evaluate the prevalence of sexually transmitted diseases, 2207 university students have been considered as control group. A complete gynecological evaluation with Pap smear and cervico-vaginal cultures were performed. Informations on sexual and behavioural patterns were collected using a standard questionnaire. IVDAs show early onset of sexual activity (15 vs. 18 yrs) and many sexual partners; just a small percentage of them use condom, efficacious in the protection against venereal diseases. These peculiar behavioural patterns and the immunodeficiency ascribable to the drug abuse may condition the high frequency of viral and bacterial infections of lower genital tract (53% vs 0.8% and 67% vs 10% respectively). Cervical intraepithelial neoplasia has been found significantly more frequently in IVDA women (16%) than in control group (1%) p less than .01.

Detection and further characterization of a newly described microsomal autoantibody associated with chronic delta infection.

Sera from 162 patients with acute or chronic hepatitis and from patients with autoimmune diseases have been investigated for autoantibodies by indirect immunofluorescence on human and animal tissues. A small proportion (14.2%) of young patients with chronic delta hepatitis has been found positive for cytoplasmic staining which was maximal in hepatocytes and renal proximal tubules. This autoantibody has been found to react with microsomal antigenic determinant different from the classic liver-kidney microsomal LKM antigen as demonstrated by fluorescence absorption experiments with purified subcellular organelles and by fluorescence-blocking tests. The microsomal autoantibody displayed also organ and species-specificity different from those shown by the LKM-positive sera. The positive patients showed persistence of the microsomal autoantibody during the follow-up without other serological markers of autoimmunity. There was no evidence of a particular course of chronic delta hepatitis in patients positive for the microsomal autoantibody.

Hepatitis B virus-associated coinfection and superinfection with delta agent: indistinguishable disease with different outcome.

Markers of hepatitis B virus (HBV) and delta agent were prospectively tested in sera of 107 intravenous drug abusers with acute hepatitis positive for hepatitis B surface antigen (HBsAg) associated with delta infection and compared with the findings in addicts with acute classical hepatitis B. On the basis of the presence and titer of IgM antibody to hepatitis B core antigen, 86 of the addicts with delta infection had simultaneously acquired HBV and delta agent, and 21 were chronic carriers of HBsAg experiencing acute delta superinfection. The frequencies of biphasic and severe hepatitis were significantly higher (P less than .05) in delta agent-infected patients than in controls, but the acute clinical and biochemical features of the two varieties of delta disease were not distinguishable. However, in analogy to the clinical outcome of classical hepatitis B, all patients with nonfatal acute HBV/delta coinfection had self-limited illness, whereas 20 of 21 HBsAg carriers superinfected by delta agent developed chronic active hepatitis.

Prolonged course and relapses of acute type A hepatitis.

Sixty-nine consecutive patients with acute type A hepatitis were followed-up to establish the natural history of the disease. Illicit drug abusers were not included in this study. 19% (13/69) of the patients at 6th month, and 6% (4/69) at 12th month showed aminotransferase (ALT) values at least two folds the upper levels. The histological examinations performed in 5 of these cases suggest that persistence of abnormal ALT levels may be related to a misdiagnosed chronic liver disease preexisting the acute type A hepatitis. Three of the 69 patients had a relapsing hepatitis with two peaks of serum ALT 6-8 weeks apart. The illness resolved uneventfully in all these patients. The exclusion of exposure to liver toxins such as alcohol or drugs, as well as other known hepatitis virus infection in these cases, suggests that the two distinct episodes of hepatitis could be the result of the sequential infection of hepatitis A and non-A, non-B viruses.

Autoantibody pattern in non-A, non-B hepatitis.

Acute and convalescent sera from 44 patients with non-A, non-B hepatitis were tested for organ and non-organ specific autoantibodies by indirect immunofluorescence. In the acute-phase sera, 36.4% of the patients were positive for smooth muscle antibodies. Brush border antibodies and anti-reticulin antibodies were detected in 13.6% of the patients. Only two patients (4.5%) were positive for anti-nuclear antibodies. The autoantibody pattern did not relate to the different epidemiology, sex, a previous hepatitis B virus infection or to the biochemical liver function tests. The autoantibody pattern did not differ statistically in patients who recovered (23 cases) and in patients who progressed to chronic liver disease (21 cases), even if a higher frequency of smooth muscle antibodies was detected in the latter group. Convalescent sera screening showed that the clinical course of the disease did not relate to the behaviour of smooth muscle antibodies, brush border antibodies and anti-reticulin antibodies. However, an increase (28.6%) in anti-nuclear antibodies in patients who progressed to chronic liver disease was observed. The clinical significance of the presence of serological markers of autoimmunity in patients with chronic sequelae following acute non-A, non-B hepatitis is discussed.