Dietary Management of the Glycogen Storage Diseases: Evolution of Treatment and Ongoing Controversies.

The hepatic glycogen storage diseases (GSDs) are a group of disorders where abnormal storage or release of glycogen leads to potentially life-threatening hypoglycemia and metabolic disturbances. Dietary interventions have markedly improved the outcome for these disorders, from a previously fatal condition to one where people can do well with proper care. This article chronicles the evolution of dietary management and treatment of the hepatic GSDs (types 0, I, III, VI, IX, and XI).

Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

Background: Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy.

Tight metabolic control plus ACE inhibitor therapy improves GSD I nephropathy.

The onset of microalbuminuria (MA) heralds the onset of glomerulopathy in patients with glycogen storage disease (GSD) type I. Unlike tubulopathy, which responds to improved metabolic control, glomerulopathy in GSD I is considered refractory to medical intervention, and it is thought to inexorably progress to overt proteinuria and renal failure. Recent reports of reduced microalbuminuria following strict adherence to therapy counter this view.

Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes.

Inflammatory and reparative tissue reaction in developing human central nervous system.

Morphologic features of inflammatory reactions in the immature central nervous system (CNS) develop in the second half of pregnancy. The cells composing the infiltrations arise early during development but their presence in circulation and final localization in fully mature inflammatory reactions is prolonged in time. The aim of this work was to compare the picture of inflammatory infiltrations in a group of fetal brains following various infections and aseptic injuries.

Cerebellar cortex lesions in cases with subtentorial neoplastic changes.

The aim of the study was to perform neuropathological examinations of the brains of children and adults with various types of neoplasms situated in the subtentorial area. In view of the varied opinions on the central nervous system (CNS) lesions in the course of neoplastic diseases, it was interesting to analyze the cerebellar cortex damage. The study material included fifteen primary tumors in children and fourteen tumors in adults.

Neuronal heterotopies and formation of cortical anomalies.

The history of neuronal disturbances of a group of cases was examined neuropathologically. The correlation between three consecutive occurrences of migration and the observed changes made it possible to establish all the modes of this process in six cases. In spite of this process, a relatively long survival of six years was observed.

Anomalies of cerebral structures in acranial neonates.

Eleven cases of newborns with acrania and macroscopically diagnosed anencephaly were neuropathologically examined. They presented changes in which 1 group corresponded to the diagnosis of aprosencephaly. In the second group, the development of prosencephalic structures was more advanced.

A case of pseudo-aprosencephaly.

We present a case of rare, severe brain malformations. In a microcephalic premature newborn only a small structure found in the base of the cranium corresponded to the prosencephalic part of the brain. The basal ganglia were lacking and the cortico-subcortical area changed into empty vesicles with only small fragments of cortical stripe.

Early occurring neuronal migration and maturation disorders.

This case report presents severe malformations of the central nervous system as a result of a pathological process occurring very early during development. Abnormal maturation and migration of neuroblasts were seen in all cerebral structures. Such changes are most often genetically determined, but in our case the analysis of their aetiology was not available.

Hypoxic damage of the cerebellum in 7-day-old rats. Ultrastructural and histochemical study.

The damaging influence of hypoxia on the cerebellum in immature rats, which is still discussed, was investigated. Using material obtained in a modified Levine model for combined hypoxic-ischemic damage in 7-day-old rats, we examined changes in cerebellum submitted to hypoxia only. The results demonstrated classic features of hypoxic nervous tissue damage and calcium accumulation in mitochondria and endoplasmic reticulum.

[Bioethics and scientific research progress].

Progress of biomedical sciences provokes ethical questions. In vitro fertilization, multiple embryos used in research, therapeutic cloning, technically possible genetic manipulations with embryos, exemplify the need to propose a uniform view regarding the beginning of human life. Numerous scientists are convinced that human life begins with fertilization, a point of establishing a genetic identity.

Accumulation, distribution and phenotype heterogeneity of mast cells (MC) in human brains with neurocysticercosis.

Neurocysticercosis (NCC) is one of the most common parasitic brain infections in the world NCC can cause widely varied clinical manifestations, mainly due to the host immune-inflammatory response. The immunological hallmark of the infection with helminth parasites is infiltration into the inflamed mucosa of the gastrointestinal tract of numerous mast cells. It has been postulated that mediators released by activated mast cells might contribute to the local inflammatory response.

The role of Glial-Pial barrier lesions and impaired vascularization in anomalous formation of cortical convolutions.

The abnormal patterns of cerebral convolutions range from severe to small anomalies restricted to tertiary gyri and sulci. Lesions within Glial-Pial barrier were found in examined cases with cortical developmental abnormalities. Anomalies and impaired function of vessels penetrating the cortex from meningeal plexus coexisted often with Glial-Pial barrier lesions.

Prosencephalic commissures dysgenesis combined with spinal neural tube defects.

The neuropathological picture of four cases of prosencephalic malformations coexisting with spinal dysraphic anomalies inclined us to discuss the nosological position of these abnormalities. The hypoplastic anomalies of prosencephalic commissures combined with well-cleaved (except for basal ganglia) brain hemispheres allow to think of failure within lamina terminalis. The observations support the opinion that described malformations are consequence of abnormal planning of prosencephalic formation.

Brain damage in children in course of neoplastic diseases.

The aim of our neuropathologic study was to evaluate the changes in the CNS of children occurring in course of neoplastic diseases. First of all we looked for those which correspond to paraneoplastic syndromes and others which could be considered as secondary toxic lesions after prolonged chemotherapy. Twenty seven brains of children aged 0-11 years, 20 without and 7 with metastatic or primary neoplastic changes within CNS were examined.

The morphological picture of developing meningo-encephalitis in central nervous system.

In this paper we are summarizing our observations collected during several years and concerning the inflammatory changes in maturing human brains. Studies of inflammatory reactions in developing central nervous system (CNS) revealed that their morphological picture changes along with the maturation of the brain and formation of fetal immune response. We have analyzed various types of inflammatory processes (meningeal infiltrations, meningoencephalitis with perivascular infiltrates and glial interstitial changes, inflammatory-necrotic lesions) occurring in different stages of brain development.

Olfactory neuroblastoma (esthesioneuroblastoma) and esthesioneuroepithelioma: histologic and immunohistochemical study.

Two cases of olfactory neuroblastoma (ONB) representing two morphological variants of the tumor are described. Case 1 exhibited a neuroblastoma-like histological pattern corresponding to the usually reported type of ONB--the esthesioneuroblastoma, whereas in case 2 a very rare variant of ONB-the esthesioneuroepithelioma was recognized. The histological and immunohistochemical differences between the cases are discussed with regard to still controversial opinions concerning the subclassification of ONB and the histogenesis and clinical prognosis of these tumors.

[Brain changes in dysraphic syndromes occurring in cases of meningomyelocele].

Neural tube defects are the most common anomalies of the CNS in the group of dysraphic syndromes. They occur on both encephalic and spinal levels. According to the title of this article we discuss some characteristic examples of intracranial, encephalic changes occurring in cases of meningomyeloceles.

The degenerative diseases or syndromes in maturing central nervous system.

The diagnosis of degenerative diseases or syndromes in the nervous system in based on their morphological picture. The changes occur in selected CNS structures or systems being induced in the course of more or less known processes sometimes with known, more often unknown etiology. Degenerative syndromes may be classified according to the topography of changes.

Ultrastructural studies of PECAM-1/CD31 expression in the developing mouse blood-brain barrier with the application of a pre-embedding technique.

The aim of this study was to investigate the time of expression of the adhesion molecule platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in the developing mouse blood-brain barrier (BBB). Ultrastructural studies employing a preembedding technique described herein demonstrate that PECAM-1 is initially expressed on the luminal and abluminal endothelial cell surfaces in the newborn animals. This adhesion molecule expression appears to increase in intensity at 7-10 days post partum and then decreases to a weak labelling of the luminal endothelial cell surfaces at two weeks after birth.

The white matter changes in microencephalic HIV infected infants. A preliminary report.

The brains of six infants 14-34 months of age and with microencephaly (brain weight deficit 20-55.5%) were chosen from a group of cases vertically infected with HIV. The center of our investigations was focused on the white matter changes of which two types were observed in the examined brains.

Astroglial reactions in periventricular white matter of maturing human brains.

The aim of the study was to examine the astroglial reactivity in brains of fetuses and newborns during the third trimester of gestation. The immuno-histochemical reaction of glial cells with glial fibrillary acidic protein (GFAP) was used. The periventricular white matter damage due to pre- and perinatal hypoxia or sepsis was examined in 11 cases of 28 to 40 weeks of developmental age.

Migration disorders leading to a wide spectrum of brain malformations in a case with multiorganic dysgeneses: A new syndrome?

A case of a preterm infant who died with multiorgan, mainly cerebro-oculo-cutaneous malformations is presented. The brain dysgenesias consist of early disturbances of neuronal migration. They result on appearance of nodular subcortical heterotopias, cortical anomalies including pachy- and polymicrogyria and focal intrusion of numerous abnormally migrating nerve cells into leptomeninges.

Different developmental rates of selected brain structures in humans.

Various rates of development are characteristic for particular structures of the human central nervous system (CNS). The differences of the maturing brain stem and telencephalon are evident in a routine neuropathological examination. The fetal and postnatal archi- and neocortex also reveals uneven levels of maturation.