Presentation
The most common form of the disease typically presents in infancy, but various other forms can present in childhood, adolescence, or even adulthood. GM2 gangliosidosis is sometimes called Tay-Sachs disease or HexA deficiency. [childrenshospital.org]
Clinical symptoms of GM1 gangliosidosis type I are presented during the first month of life. [bmcmedgenet.biomedcentral.com]
Ballooned neurons are present throughout the CNS. Clinical variation is noted. [emedicine.medscape.com]
Similarly, 5 non-consanguineous Galician heterozygous B1 variant carriers were identified, with all cases presenting the R178H mutation. [scielo.br]
The mean time from the initial presenting symptoms to the diagnosis was 7.5 ± 8.3 years (range: 0.3–26.8 years). [ncbi.nlm.nih.gov]
Entire Body System
- Asymptomatic
[…] year-old Hungarian man with no known Jewish ancestry was diagnosed with late-onset TSD following genetic testing, which identified a heterogeneous pathogenic mutation with both 1499T deletion and an 805G>A substitution in the HEXA gene. [11] Clinically asymptomatic [emedicine.medscape.com]
Gastrointestinal
- Nausea
Miglustat also inhibits disaccharidases in the gut, which leads to gastrointestinal symptoms of diarrhea, nausea, and abdominal pain if carbohydrates in the diet are not reduced [21]. [ncbi.nlm.nih.gov]
- Failure to Thrive
Early symptoms include poor appetite, weak suck and failure to thrive. Only about 50% of cases display the cherry-red spot in the back of the eye. [ntsad.org]
Liver, Gall & Pancreas
- Hepatosplenomegaly
In type II of the disease, patients usually do not present distinctive facial features, hepatosplenomegaly and cherry red spot, making the diagnosis perplexed. [bmcmedgenet.biomedcentral.com]
As the disease progresses, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, seizures, profound intellectual disability, and clouding of the clear outer covering of the eye (the [medlineplus.gov]
However, with Sandhoff's disease there is a gross pathology in the visceral organs, such as endocardial fibrosis and hepatosplenomegaly (1). [scielo.br]
Skin
- Macula
A doctor may notice red spots in the back of the eye (cherry-red spots of the macula) and an abnormal reflex of the foot that indicates damage to the nervous system (the Babinski reflex). [rarediseases.org]
Ophthalmoscopic examination The cherry-red central spot or perifoveal white patch seen in the retinal fovea centralis of the retinal macula of those affected with infantile and juvenile TSD is not seen in those affected with chronic TSD. [emedicine.medscape.com]
Other clinical symptoms A cherry-red spot was observed in the macula of the eye in all three subjects with liTS and in 2 of 3 subjects with jTS, and faint haze in each macula in the third subject with jTS. [ncbi.nlm.nih.gov]
Musculoskeletal
- Muscle Spasticity
They can also have trouble with feeding, overreaction to loud sudden noises, delayed speech, early blindness, seizures, heart murmur, and continuously tight muscles (spasticity). [rarediseases.org]
Psychiatrical
- Psychomotor Retardation
Progressive cerebral ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10 year-old child: juvenile Sandhoff disease. Neurology 1977;27:571-573. Rubin M, Karpati G, Wolfe LS, et al. [rarediseases.org]
The Arg201Cys mutation, eliminating a BspMI site, was previously identified in a late-infantile/juvenile patient who had psychomotor retardation/deterioration, dysostosis multiplex, and hepatosplenomegaly. [bmcmedgenet.biomedcentral.com]
Progressive cerebellar ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10-year-old child: juvenile Sandhoff disease. Neurology. 1977;27:571–573. [PubMed] [Google Scholar] 38. Brandt S, Clausen J, Diemer NH, et al. [ncbi.nlm.nih.gov]
Neurologic
- Agitation
Psychiatric abnormalities include acute hebephrenic schizophrenia, agitation, delusions, hallucinations, paranoia, and recurrent depression that may precede neurologic defects, but dementia is usually not prominent. [emedicine.medscape.com]
- Apathy
Most patients never walk and exhibit increasing apathy and inattention. Hyperacusis (ie, persistent extension response to sound, startle reaction) can aid in early diagnosis. [emedicine.medscape.com]
- Behavior Problem
Behavioral or psychiatric problems, proximal and distal weakness, and muscle wasting also tended to appear late in the disease course. [ncbi.nlm.nih.gov]
- Tremor
Neurologic defects progress slowly and may lead to lack of coordination; hand tremors; progressive dystonia; dysarthria, dyskinesia; choreoathetosis; ataxia; spinocerebellar degeneration; motor neuron disease with proximal muscle wasting, cramping, and [emedicine.medscape.com]
- Convulsions
In general the pathology is very similar for the classic forms of Sandhoff's and Tay-Sachs disease, and deficiency of the GM2 activator, with involutional neurodegenerative symptoms, associated with alterations of language, deambulation, dystonia, convulsions [scielo.br]
Workup
Workup and physical examination Both homozygotes and heterozygotes have a reduced concentration of sphingomyelin in their RBCs. Affected individuals have deficient Hex A activity and normal levels of the Hex B isozyme. [emedicine.medscape.com]
Treatment
Research has included Gene Therapy, Molecular Chaperone, Substrate Inhibition, Stem Cells, and Bone Marrow Treatment. [ntsad.org]
Signs and symptoms may include: slowing of growth plateau of gross and fine motor development developmental regression poor muscle tone (hypotonia) exaggerated startle reaction seizures visual impairment hearing loss intellectual disability Treatment [childrenshospital.org]
No treatments are currently approved for the gangliosidoses, and development of treatments is impaired by limited understanding of the natural history of these diseases. [ncbi.nlm.nih.gov]
Medical care Enzyme replacement has not yet been successful. [13] Because no specific treatment is available for TSD, treatment is directed at the symptoms and major associated conditions. [emedicine.medscape.com]
Supportive treatment includes ensuring proper nutrition and hydration, keeping the airway open, and seizure control with anticonvulsants. Genetic counseling is recommended for affected individuals and their families. [rarediseases.org]
Prognosis
This subacute phenotype of the B1 variant could be due to the presence of a defective allele, with the mutated Hex A conserving a residual in vivo activity against the GM2 ganglioside (1,7), although the prognosis of the disease is poor, with rapid deterioration [scielo.br]
Prevention
GM2 gangliosidosis is most often caused by a mutation in the HEXA or the GM2A gene, which prevents an enzyme called beta-hexosaminidase A from properly breaking down large molecules inside the body’s cells. [childrenshospital.org]
In 1970, TSD became the prototype for genetic disease prevention. North American individuals with a family history positive for a GM2 gangliosidosis or Ashkenazi Jewish heritage agreed to be tested. [emedicine.medscape.com]
In Tay-Sachs disease, mutations in the HEXA gene result in a defective α-subunit [4], whereas in Sandhoff disease, mutations in the HEXB gene prevent normal β-subunit production [[1], [2], [3]]. [ncbi.nlm.nih.gov]