Biochemical and clinical response after umbilical cord blood transplant in a boy with early childhood-onset beta-mannosidosis.

BACKGROUND: Deficiency in the enzyme β-mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood-onset β-mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available. METHODS: We report 2-year outcomes following the first umbilical cord blood transplant in a 4-year-old boy with early childhood-onset disease. RESULTS: We show restoration of leukocyte β-mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β-mannosidase activity and dramatic decrease in urine-free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers. CONCLUSION: Our findings suggest that hematopoietic cell transplant can correct the biochemical defect in β-mannosidosis, although preservation of the neurocognitive trajectory may be a challenge

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome

The Antibacterial Effect <em>In Vitro</em> of Honey Derived from Various Danish Flora

The mechanism behind the biologic actions of honey as a wound remedy has been intensively studied; however, there is no published data regarding any antibacterial effect of honey derived from Danish flora. We surveyed 11 honeys of various Danish floral sources for their antibacterial activity and compared them to a culinary processed commercial honey (Jakobsens) and a raw and a medical grade Manuka (Leptospermum scoparium) honey using the agar-well diffusion method. We tested the effect on three gram-positive bacteria (two strains of Staphylococcus aureus and one strain of Staphylococcus epidermidis) and two gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). All samples, except the commercial honey, exhibited antibacterial activity, and samples derived from Water Mint (Mentha aquatica), Organic 2 (mixed organic flora), and Linden (Tilia cordata) honey had consistent effects on all bacteria tested and showed greater effect than medical grade and raw Manuka (L. scoparium) honey. The content of methylglyoxal was low in the Danish honey (< 2 μg/mL) and significantly (p<0.05) higher in both the raw and the medical grade Manuka (L. scoparium) honey, where the concentrations were, respectively, 6.29 μg/mL and 54.33 μg/mL. The antibacterial effect of Danish honeys was mostly due to hydrogen peroxide. We conclude that honeys derived from Danish flora possess antibacterial effect, probably by a hurdle effect of viscosity, osmolality, acidity, bioactive peptides, and most importantly the content of hydrogen peroxide. These findings indicate that honeys of various Danish floral sources may have clinical potential, although further studies are necessary to elucidate this in order to determine whether the results of our in vitro experiments also apply to a clinical setting

Children with Albinism in African Regions::Their rights to ‘being’ and ‘doing’

Abstract Background Albinism is an inherited condition with a relatively high prevalence in populations throughout sub-Saharan Africa. People with oculocutaneous albinism have little or no pigment in their hair, skin and eyes; thus they are visually impaired and extremely sensitive to the damaging effect of the sun on their skin. Aside from the health implications of oculocutaneous albinism, there are also significant sociocultural risks. The impacts of albinism are particularly serious in areas that associate albinism with legend and folklore, leading to stigmatisation and discrimination. In regions of Africa those with albinism may be assaulted and sometimes killed for their body parts for use in witchcraft-related rites or to make ‘lucky’ charms. There is a dearth of research on the psychosocial aspects of albinism and particularly on how albinism impacts on the everyday lives of people with albinism. Discussion There is a growing recognition and acceptance in Africa that people with albinism should be considered disabled. Thomas’s social-relational model of disability proposes it is essential to understand both the socio-structural barriers and restrictions that exclude disabled people (barriers to doing); and the social processes and practices which can negatively affect their psycho-emotional wellbeing (barriers to being). In this article, we combine a social model of disability with discussion on human rights to address the lacuna surrounding the psychosocial and daily experiences of people with albinism. Conclusion Through using this combined framework we conclude that the rights of people with albinism in some regions of Africa are not being enacted. Our debate highlights the need to develop a holistic concept of rights for children and young people with albinism which sees human rights as indivisible. We illuminate some of the specific ways in which the lives of children with albinism could be improved by addressing ‘barriers to being’ and ‘barriers to doing’, at the heart of which requires a shift in attitude and action to address discrimination