Presentation
The data presented here provide new insight into the NEU1-cathepsin A complex. We further present a proof-of-concept study for pharmacological chaperone therapy using inhibitors targeting NEU1 for the treatment of sialidosis and galactosialidosis. [scholarworks.umass.edu]
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. [ncbi.nlm.nih.gov]
Entire Body System
- Ascites
After birth she received intensive treatment that led to improvement of edema and pleural effusion, but ascites slowly developed. She died of renal failure on day 207. [ncbi.nlm.nih.gov]
We describe a newborn female in whom massive ascites and signs of left ventricu- lar hypertrophy were seen on ultrasound at the gestational age of 31 weeks. [deepdyve.com]
The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. [uniprot.org]
- Anemia
It may be necessary to treat symptoms of the worm infection such as iron deficiency anemia through dietary means or iron supplements. In severe cases of anemia, a blood transfusion may be required. Are there any clinical trials underway? Yes. [raregenomics.org]
[…] deficiency Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome Congenital disorder of glycosylation Congenital dyserythropoietic anemia [se-atlas.de]
Laboratory tests revealed anemia [hemoglobin (Hb) 9.0 g/dL], neutropenia [white blood cell (WBC) count 3.920/mm 3 ], hypocalcemia (6.9 mg/dL; reference range 8.7-10.4 mg/dL), hypophosphatemia (3.48 mg/dL; reference range 4.5-6.5 mg/dL) and elevated alkaline [content.sciendo.com]
He was later found to have anemia and thrombocytopenia and evidence of hemophagocytosis of erythrocytes, thrombocytes, lymphocytes, and granulocytes by the foamy cells that develop in this disorder. [ncbi.nlm.nih.gov]
Gastrointestinal
- Failure to Thrive
Common symptoms in all four patients included facial dysmorphisms, hypotonia, developmental delay, failure to thrive, liver-spleen-megaly and ascites (Table 1 ). Respiratory distress and cardiac involvement, when investigated, were also observed. [doi.org]
The newborn developed severe psychomotor delay, showed failure to thrive and had recurrent respiratory infections. [scielo.br]
[…] syndrome Hypoalphalipoproteinemia Hypobetalipoproteinemia Hypotonia with lactic acidemia and hyperammonemia Hypotonia-cystinuria syndrome Hypotonia-cystinuria type 1 syndrome Hypotonia-failure to thrive-microcephaly syndrome Hypoxanthine guanine phosphoribosyltransferase [se-atlas.de]
Liver, Gall & Pancreas
- Hepatosplenomegaly
This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and “coarse” facial features. [ismrd.org]
Adrenal hyperplasia and thickening of the cardiac septum were detected by sonography; however, progressive hepatosplenomegaly, increasingly coarse features, and vacuolization of bone marrow and liver cells suggested a storage disorder. [ncbi.nlm.nih.gov]
This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and "coarse" facial features. [nzord.org.nz]
Fetus
- Hydrops Fetalis
We present a case of hydrops fetalis where routine placental examination showed a heavy and large placenta for gestational age. [hindawi.com]
The early infantile form is associated with hydrops fetalis, visceromegaly, skeletal dysplasia, and early death. [ggc.org]
Abstract At the 28th week of gestation a hydrops fetalis was first detected by ultrasound. At birth a generalized hydrops with Hurler-like craniofacial dysmorphism, hepatosplenomegaly and a moderate dystostosis multiplex was noted. [ncbi.nlm.nih.gov]
The early infantile form of galactosialidosis is associated with extensive swelling caused by fluid accumulation before birth (hydrops fetalis), a soft outpouching in the lower abdomen (an inguinal hernia), and an enlarged liver and spleen (hepatosplenomegaly [ismrd.org]
The early infantile form is the most severe form, which may also appear as non immune hydrops fetalis. Specific therapy for galactosialidosis is not available at present [ 1, 5, 6 ]. [content.sciendo.com]
Skin
- Angiokeratoma
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. [ncbi.nlm.nih.gov]
The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. [uniprot.org]
It is characterized by coarse facial features, macular cherry-red spots, angiokeratoma (dark red spots on the skin), vertebral deformities, epilepsy, action myoclonus, and ataxia. [globalgenes.org]
People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, “coarse” facial features, a cherry-red spot, vision loss, and hearing loss. [ismrd.org]
- Skin Rash
rash-neurological manifestations syndrome Pentosuria Periodic paralysis with later-onset distal motor neuropathy Peroxisomal acyl-CoA oxidase deficiency Peroxisomal beta-oxidation disorder Peroxisomal disease Peroxisome biogenesis disorder Perrault syndrome [se-atlas.de]
Musculoskeletal
- Muscle Twitch
This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and progressive intellectual disability. [ismrd.org]
An individual with the juvenile/adult form has a normal life expectancy, but can suffer from the following symptoms: Difficulty coordinating movements Muscle twitches Seizures Progressive loss of intellectual faculties Dark red spots on skin Bone abnormalities [huntershope.org]
Ears
- Hearing Impairment
Showing of 18 | 80%-99% of people have these symptoms Abnormal vertebral morphology 0003468 Cherry red spot of the macula 0010729 Coarse facial features Coarse facial appearance 0000280 Corneal opacity 0007957 Hearing impairment Deafness Hearing defect [rarediseases.info.nih.gov]
Neurologic
- Myoclonus
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. [ncbi.nlm.nih.gov]
The myoclonus subsequently spreads to other body regions. Five years into the disease, she was almost wheelchair bound, and other activities such as eating and speaking were considerably affected. [ri.conicet.gov.ar]
The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. [uniprot.org]
It is characterized by coarse facial features, macular cherry-red spots, angiokeratoma (dark red spots on the skin), vertebral deformities, epilepsy, action myoclonus, and ataxia. [globalgenes.org]
Characteristic clinical presentation of the juvenile/adult form includes myoclonus, neurological deteroration, ataxia and angiokeratoma. Visceromegaly, such as hepatosplenomegaly, is absent in this form of the disease. [themedicalbiochemistrypage.org]
- Neurologic Manifestation
In general, the patients exhibit multi-systemic symptoms mostly involving severe neurological manifestations. Tlle severity and onset of the symptoms range frlom neonatal to adulthood and ofte!n correlate with the level of residual enzyme activity. [repub.eur.nl]
[…] late onset of neurologic manifestations. [ncbi.nlm.nih.gov]
[…] onset Niemann-Pick disease type C, juvenile neurologic onset Niemann-Pick disease type C, late infantile neurologic onset Niemann-Pick disease type C, severe early infantile neurologic onset Niemann-Pick disease type C, severe perinatal form Niemann-Pick [se-atlas.de]
- Dysarthria
[…] limb-girdle muscular dystrophy type 2O Autosomal recessive limb-girdle muscular dystrophy type 2T Autosomal recessive limb-girdle muscular dystrophy type 2U Autosomal recessive optic atrophy, OPA7 type Autosomal recessive spastic ataxia-optic atrophy-dysarthria [se-atlas.de]
- Spastic Quadriplegia
[…] ataxia-optic atrophy-dysarthria syndrome Autosomal recessive spastic paraplegia type 39 Autosomal recessive spastic paraplegia type 55 Autosomal recessive spondylocostal dysostosis B4GALT1-CDG Barth syndrome Beta-ketothiolase deficiency Beta-mannosidosis [se-atlas.de]
Urogenital
- Kidney Failure
Some infants have an enlarged heart (cardiomegaly); an eye abnormality called a cherry-red spot, which can be identified with an eye examination; and kidney disease that can progress to kidney failure. [ismrd.org]
[…] disease that can progress into kidney failure Late Infantile Form The late infantile form of galactosialidosis is similar to early infantile form, with a few exceptions. [huntershope.org]
- Renal Insufficiency
In this report, we present a 9-month-old early infantile Galactosialidosis infant with renal involvement. In the literature only isolated cases of Galactosialidosis with IgA nepropathy, renal insufficiency and renal transplantation reported. [omicsonline.org]
Based on clinical manifestations and age of onset of the disease, three clinical phenotypes are now distinguished: a severe early infantile form, fatal at or soon after birth, and associated with fetal hydrops, CNS involvement, visceromegaly, renal insufficiency [nature.com]
Workup
It may prove to be a great tool in the workup of complicated pregnancies, including but not limited to intrauterine death, perinatal death, intrauterine growth restriction, and hydrops fetalis [4]. [hindawi.com]
A diagnostic workup in an individual with GM1 gangliosidosis, Morquio B, or galactosialidosis typically demonstrates decreased beta-galactosidase enzyme activity in leukocytes or fibroblasts; however, additional testing and consideration of the patientâ [mayomedicallaboratories.com]
Serum
- Hyperammonemia
[…] to methylene tetrahydrofolate reductase deficiency Homocystinuria without methylmalonic aciduria Homozygous familial hypercholesterolemia Hurler syndrome Hurler-Scheie syndrome Hyaluronidase deficiency Hyper-beta-alaninemia Hyperalphalipoproteinemia Hyperammonemia [se-atlas.de]
Treatment
NEU1 activity is deficient in sialidosis and galactosialidosis, and there are no available treatments for both the diseases. [scholarworks.umass.edu]
However, in fibroblasts from the second galactosialidosis subject, the amount of the abnormal 72 kDa polypeptide was not influenced by leupeptin treatment. [ncbi.nlm.nih.gov]
Treatment is symptomatic and supportive; for example, taking medication to control seizures. [rarediseases.info.nih.gov]
Is there a Treatment for Galactosialidosis? There is no cure for galactosialidosis. Treatment is symptomatic and supportive; for example, taking medication to control seizures. [nzord.org.nz]
Prognosis
However homozygous Q49R mutation detected in our case was severe prognosis. [ncbi.nlm.nih.gov]
Bone marrow transplant is under investigation as an experimental therapy. [4] [5] No conclusive results are currently available regarding the long term benefits of this treatment. [5] Last updated: 5/16/2011 Prognosis depends upon the type of galactosialidosis [rarediseases.info.nih.gov]
Prognosis The prognosis for individuals with this disorder varies greatly depending on the specific genetic mutation, which determines the age of onset and severity of the disease. [encyclopedia.com]
Etiology
[…] clinical diagnostics defines disease diagnosis by a specified spectrum of phenotypic findings; when such parameters are either missing, or other findings not usually observed are seen, the phenotype driven approach to diagnosis may result in a specific etiological [ncbi.nlm.nih.gov]
Berghella, “Lysosomal storage disease as an etiology of nonimmune hydrops,” American Journal of Obstetrics and Gynecology, vol. 212, no. 3, pp. 281–290, 2015. View at: Publisher Site | Google Scholar R. Froissart, D. Cheillan, R. [hindawi.com]
Epidemiology
Although worldwide epidemiological data on LSDs is limited, as a group, the incidence is estimated at around 1 : 5,000–1 : 8,000 [1]. [hindawi.com]
Nugent AW, Daubeney PE, Chondros P et al. (2003) The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 348:1639–1646 CrossRef PubMed Google Scholar 16. [link.springer.com]
Pathophysiology
The combined use of immunoprecipitation and immunostaining was useful for analysing the pathophysiology of the intracellular processing and transport of the mutant beta-galactosidase. [ncbi.nlm.nih.gov]
Achyuthan, Comparative enzymology, biochemistry and pathophysiology of human exo-α-sialidases (neuraminidases), Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 129, 1, (29), (2001). [doi.org]
Prevention
In two EI and one J/A patient, we have identified four novel point mutations (Val104Met, Leu208Pro, Gly411Ser and Ser23Tyr), that prevent phosphorylation and, hence, lysosomal localization and maturation of the mutant precursors. [ncbi.nlm.nih.gov]
Succinct, targeted coverage of normal childhood growth and development, as well as the diagnosis, management, and prevention of common pediatric diseases and disorders, make this an ideal medical reference book for students, pediatric residents, nurse [books.google.com]
(PMID: 19954752) Reich M … Burster T (Immunology letters 2010) 3 22 60 Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization. [genecards.org]
In galactosialidosis, toxic materials accumulate within the cells because of an enzyme deficiency that prevents the lysosomes from performing their functions. [raregenomics.org]