1/24. Clinical spectrum of infantile free sialic acid storage disease.Infantile free sialic acid storage disease (ISSD) is a rare autosomal recessive metabolic disorder caused by a lysosomal membrane transport defect, resulting in accumulation of free sialic acid within lysosomes. Only a few cases have been described. We report on three new cases of ISSD with different modes of presentation: an infant with nephrotic syndrome, a case of fetal and neonatal ascites with heart failure, and a case of fetal ascites with esophageal atresia type III. From these patients and a review of the literature (27 cases total) we draw the following conclusions. 1) "Coarse facies," fair complexion, hepatosplenomegaly, and severe psychomotor retardation are constant findings in this disorder. 2) nephrotic syndrome occurred in most cases (four in seven) in which renal evaluation was performed. Therefore, ISSD is an important cause of nephrosis in infants with a storage disorder phenotype. 3) Fetal/neonatal ascites or hydrops was the mode of presentation in 13 (60%) of 21 cases. Thus, ISSD enters in the differential diagnosis of hydrops fetalis with a storage disease phenotype. 4) cardiomegaly was evident in nine cases. 5) Corneae were always clear, and albinoid fundi were reported in five cases. 6) Dysostosis multiplex was not prominent. 7) bone marrow aspiration could be negative. 8) death ensued in early infancy with a mean age of 13.1 months. All reported deaths were caused by respiratory infections.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
2/24. Clinical, pathologic, and neurochemical studies of an unusual case of neuronal storage disease with lamellar cytoplasmic inclusions: a new genetic disorder?A child of first-cousin Puerto Rican parents had global developmental delay, failure to thrive, and hypotonia since early infancy. At 1 1/2 years of age, she developed clinical and electrophysiologic evidence of progressive motor and sensory neuropathy. At 2 1/2 years, she developed visual impairment and optic atrophy followed by gradual involvement of the 7th, 9th, 10th, and 12th cranial nerves. Uncontrollable myoclonic seizures began at 4 years and she died at 6 years of age. Motor nerve conduction velocities were initially normal and later became markedly slowed. Sensory distal latency responses were absent. Lysosomal enzyme activities in leukocytes and fibroblasts were normal. sural nerve and two muscle biopsies showed only nondiagnostic abnormalities. Electron microscopy of lymphocytes, skin, and fibroblasts showed cytoplasmic inclusions. light microscopy of frontal cortex biopsy showed neuronal storage material staining positively with Luxol fast blue, and electron microscopy showed cytoplasmic membranous bodies in neurons, suggesting an accumulation of a ganglioside. At autopsy, all organs were small but otherwise normal and without abnormal storage cells in the liver, spleen, or bone marrow. Anterior spinal nerve roots showed loss of large myelinated axons. The brain was small and atrophic; cortical neurons showed widespread accumulation of storage material, most marked in the pyramidal cell layer of the hippocampus. Subcortical white matter was gliotic with loss of axons and myelin sheaths. In cortical gray matter there was a 35% elevation of total gangliosides, with a 16-fold increase in GM3, a three- to four-fold increase in GM2 gangliosides, and a 15-fold elevation of lactosyl ceramide. GM3 sialidase activity was normal in gray matter at 3.1 nmols/mg protein per hour and lactosyl ceraminidase I and II activities were 70% to 80% of normal. In white matter, total myelin was reduced by 50% but its composition was normal. Phospholipid distribution and sphingomyelin content were normal in gray matter, white matter, and in the liver. These biochemical findings were interpreted as nonspecific abnormalities. The nature of the neuronal storage substance remains to be determined.- - - - - - - - - - ranking = 0.00046642068181595keywords = brain (Clic here for more details about this article) |
3/24. Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up.Galactosialidosis (GS) is an autosomal recessive condition caused by combined deficiency of the lysosomal enzymes beta-galactosidase and alpha-neuraminidase. The combined deficiency has been found to result from a defect in protective protein/cathepsin a (PPCA), an intralysosomal protein which protects these enzymes from premature proteolytic processing. The most severe form of GS, the early-infantile form, results in early onset of edema, ascites, visceromegaly, and skeletal dysplasia. We report a case of early-infantile GS in a male infant who presented with nonimmune fetal hydrops (NIH), "coarse" facial appearance, massive fluid-filled inguinal hernias, multiple telangiectasia, and diffuse hypopigmentation; he subsequently developed visceromegaly. The diagnosis of GS was confirmed biochemically and the defect in PPCA characterized at the protein level. Examination of fetal peripheral blood smears sampled at 30 weeks gestation demonstrated vacuolation of lymphocytes, suggesting blood film examination may be a useful screening tool for cases of NIH where a metabolic disorder is suspected. Skeletal radiography at birth demonstrated punctate epiphyses of the femora, calcanei, and sacrum. We present a discussion of and differential diagnosis for this radiographic finding. To the best of our knowledge, this is the first case of early-infantile GS presenting with stippled epiphyses.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
4/24. Refractory congenital ascites as a manifestation of neonatal sialidosis: clinical, biochemical and morphological studies in a newborn Syrian male infant.A Syrian newborn with coarse facies, hepato-splenomegaly, and refractory ascites is reported. Examination of the ascitic fluid showed vacuolated lymphocytes and thin-layer chromatography of urinary oligosaccharides revealed an abnormal pattern indicative of sialidosis. Despite intensive care, the baby died of respiratory insufficiency 28 days after birth. In cultured skin fibroblasts an increase of the incorporation of [14C]methylamine pointed to excessive lysosomal storage and the demonstration of an isolated deficiency of alpha-N-acetylneuraminidase (sialidase) led to the diagnosis of a sialidosis. At postmortem examination, foam cells were found mostly in bone marrow, liver, and brain. To date very few cases of neonatal sialidosis have been reported, and, to the best of our knowledge, this is the first child with neonatal sialidosis from syria and the first case of neonatal sialidosis studied by the [14C]methylamine incorporation assay.- - - - - - - - - - ranking = 0.00046642068181595keywords = brain (Clic here for more details about this article) |
5/24. Lipoid proteinosis. A biochemical and ultrastructural investigation of two new cases.Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and visceral lesions, in which large amounts of amorphous material are constantly found in stroma. Morphological and biochemical studies indicate abnormal collagen production, but little attention has been paid to the lipid component of lesions. Microscopic and ultrastructural studies of skin, with special emphasis on fibroblasts, vessels, nerve endings and eccrine sweat glands, were conducted in two patients with lipoid proteinosis. Biochemical studies were undertaken in cultured fibroblasts. Evidence of lysosomal storage in epithelial cells of eccrine sweat glands and in dermal histiocytes, very similar to that found in some metabolic disorders, particularly Farber disease, was found in both cases. Our findings suggest that two alterations might coexist in lipoid proteinosis, one characterized by impaired normal collagen production and the other related to a metabolic defect which may lead to accumulation of ceramide or more complex lipids.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
6/24. Vascular pathology in galactosialidosis.This article immunohistochemically and ultrastructurally examines a brain with galactosialidosis, focusing on the structure of blood vessel endothelium. lysosomes were observed in the expanded cytoplasm of the endothelial cells, which were vacuolated by light microscopy. Immunoreactivity for CD31, one of the vascular cell adhesion molecules, was minimal to faint in endothelial cells with vacuolations. The loss of CD31 immunoreactivity and breakdown of vascular cell adhesion molecules in vacuolated endothelial cells seem to promote the development of brain infarctions. Moreover, diffuse and various degrees of axonal damage, most likely caused by vascular disorder in cerebral or cerebellar white matter, was reported using the amyloid precursor protein (APP) immunohistochemical method.- - - - - - - - - - ranking = 0.00093284136363189keywords = brain (Clic here for more details about this article) |
7/24. A case of galactosialidosis.Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, caused by a defect of another lysosomal protein, the protective protein. Three subtypes are recognized: the early infantile form, the late infantile form and the juvenile/adult form. We saw a patient with galactosialidosis of the juvenile/adult form, a 51-year-old Japanese man with angiokeratomas on both elbows and knees, myoclonus, ataxia, mental retardation and macular cherry-red spots. An electron-microscopic study of a skin biopsy showed membrane-limited vacuoles in the cytoplasm of the endothelial cells, pericytes and fibroblasts. Assays of enzymatic activity in cultured fibroblasts showed a marked decrease in both beta-galactosidase and neuraminidase (sialidase). The substance contained in the cytoplasmic vacuoles appears to be glycoproteins with sialic acid, which is a terminal glycosyl residue, because the cytoplasm of the endothelial cells of the vessels and pericytes are stained by the Limax flavus agglutinin, a lectin that binds specifically with sialic acid. This technology may be useful for easy investigation of the distribution of the accumulation of such substances in the central nervous system.- - - - - - - - - - ranking = 0.0029005335206306keywords = central nervous system, nervous system (Clic here for more details about this article) |
8/24. Successful hematopoietic stem cell transplantation in Farber disease.Farber disease, a lysosomal storage disorder, has a dismal prognosis leading to death with progressive granulomatous inflammation, even in patients without central nervous system involvement (type 2/3). We report the first successful hematopoietic stem cell transplantations in 2 patients with Farber disease type 2/3, resulting in resolution of symptoms.- - - - - - - - - - ranking = 0.0029005335206306keywords = central nervous system, nervous system (Clic here for more details about this article) |
9/24. Pseudo-lysosomal storage disease caused by EMLA cream.prilocaine-lidocaine emulsion (EMLA cream) is a topical anaesthetic commonly used prior to diagnostic and therapeutic procedures. While undergoing clinical investigation for the suspicion of a metabolic disorder, a series of children underwent skin biopsy with EMLA cream pretreatment. In each case, the pathologist identified ultrastructural features consistent with a lysosomal storage disorder, yet the clinical features were not consistent with the pathological findings. Ultrastructural artefact was suspected, resulting from the use of the EMLA cream. All patients underwent repeat skin biopsy without EMLA cream. Biopsies were reviewed by two pathologists blinded to the previous biopsy findings. Electron microscopy repeated without the use of EMLA cream was normal. It is concluded that the use of EMLA cream causes ultrastructural artefact and should be avoided prior to skin biopsy for electron microscopy.- - - - - - - - - - ranking = 1keywords = metabolic disorder (Clic here for more details about this article) |
10/24. Farber disease: an ultrastructural study. Report of a case and review of the literature.A case of Farber disease is reported and the ultrastructural pathology of the disease is reviewed. The present case showed the typical clinical picture of Farber disease. acid ceramidase deficiency was demonstrated biochemically. Ultrastructural features of one subcutaneous nodule and a skin biopsy are described. Three lysosomal inclusions characterize Farber disease: curvilinear tubular bodies observed mainly in the reticuloendothelial system, "banana bodies" recorded only in the peripheral nervous system and zebra-like bodies which are essentially a neuronal storage. The nature of each is discussed and the skin biopsy is emphasized for its important diagnostic interest.- - - - - - - - - - ranking = 0.0010348507933668keywords = nervous system (Clic here for more details about this article) |
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