Present case is a one year old male born to 3rd degree consanguineous Indian parents from Maharashtra. He was presented with global developmental delay, hypotonia and sensitive to hyperacusis. [ncbi.nlm.nih.gov]

Macular cherry-red spots, facial dysmorphism, hepatosplenomegaly, and generalized skeletal dysplasia are usually present in infantile cases. [ommbid.mhmedical.com]

• Choking

  As of 1/20/18 Eli's swallowing disturbance is including terrible choking episodes, even though he is tube fed only at this point (age 8). He has choking episodes from choking on spit up or thick saliva or secretions.) [gm1gangliosidosis.blogspot.com]

• Skin Lesion

  Abstract We describe an autopsy case of a 1-year-old male baby presenting with failure to gain milestones, floppiness, and reddish skin lesions since birth. Fundoscopic examination revealed bilateral cherry-red spots in the macula. [ncbi.nlm.nih.gov]

  Figure 1: Numerous, diffuse ecchymoses and Mongolian spots on ventral surface of the trunk Click here to view Figure 2: Numerous, diffuse ecchymoses and Mongolian spots on dorsal surface of the trunk Click here to view The hyperpigmented skin lesions [e-ijd.org]

• Hyperpigmentation

  Abstract Congenital dermal melanocytosis (CDM) is a birthmark composed of macular blue-grey hyperpigmentation commonly observed in the lumbosacral region of infants. [ncbi.nlm.nih.gov]

  […] growth factor and tyrosine kinase-type receptor interactions. [11] Ochiai et al. described seven Japanese boys with Hunter's syndrome and reported extensive Mongolian spots in all of them; the authors suggested that the extent and persistence of the hyperpigmentation [e-ijd.org]

• Retinal Hemorrhage

  (Eli has had three eye surgeries to correct this, before his diagnosis) Optic atrophy - the optic nerve, which carries impulses from the eye to the brain begins to waste away or deteriorate Retinal hemorrhage is a disorder of the eye in which bleeding [gm1gangliosidosis.blogspot.com]

• Impulsivity

  (Eli has had three eye surgeries to correct this, before his diagnosis) Optic atrophy - the optic nerve, which carries impulses from the eye to the brain begins to waste away or deteriorate Retinal hemorrhage is a disorder of the eye in which bleeding [gm1gangliosidosis.blogspot.com]

• Withdrawn

  One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. [ncbi.nlm.nih.gov]

• Incontinence

  Muscle wasting (10.6 +/- 7.4 years), proximal weakness (11.1 +/- 7.7 years), and incontinence of sphincters (14.6 +/- 9.7 years) appeared later in the course of the disease. [ncbi.nlm.nih.gov]

• Swelling of the Scrotum

  Reproductive System Swelling of the scrotum Other Rare symptoms Angiokeratoma corporis diffusum (reported infrequently) also called Fabry diseas e Hydrops fetalis (has been reported) - is a serious condition in which abnormal amounts of fluid build up [gm1gangliosidosis.blogspot.com]

• Speech Deterioration

  Speech deterioration progressed more rapidly than gait abnormalities in both the Tay-Sachs variant and Sandhoff variant groups. Among patients with the Tay-Sachs variant, the HEXA genotype showed a significant correlation with the clinical course. [ncbi.nlm.nih.gov]

• Dysesthesia

  A dramatic response of the severe dysesthesias to amitriptyline and gabapentin is described. Symptomatic sensory neuropathy may be a component of late-onset GM2 gangliosidosis. [ncbi.nlm.nih.gov]

Workup for her over several years included routine blood tests, alpha-fetoprotein, vitamin E, copper, and ceruloplasmin titers, which were negative. [movementdisorders.org]

Ensuing blood tests came back inconclusive and Armand’s parents, Tim Hayes and Lindy Sutton, were referred to Cincinnati Children’s Hospital Medical Center where a full workup was ordered including an MRI, muscle biopsy, chest x-rays and a DNA workup. [daytondailynews.com]

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]

We report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. [ncbi.nlm.nih.gov]

This review outlines current knowledge pertaining the pathobiology as well as potential innovative treatments for the GM2 gangliosidoses. [eurekaselect.com]

Management and treatment Treatment for patients with GM1 gangliosidosis is symptomatic and supportive. Substrate reduction therapy is a potential approach for clinical trials in late-onset forms. [orpha.net]

Prognosis Prognosis depends on the type of GM1 gangliosidosis and is extremely poor in the severe infantile form and variable in the chronic adult form of the disease. [orpha.net]

Diagnosis and Prognosis: This is a serious, progressive disease that leads to early death in all but adult patients. No treatment is effective in altering the course of the condition. [disorders.eyes.arizona.edu]

[…] bilateral globus pallidi in a “wish bone” distribution, suggestive of mineralization Click here to view In our patient, childhood-onset progressive dystonia with prominent orofacial and laryngeal involvement and auditory startle suggested a secondary etiology [neurologyindia.com]

Etiology The disorder is caused by mutations in the GLB1 gene (3p22.3) coding for beta-galactosidase. To date, more than 165 mutations have been identified. [orpha.net]

Summary Epidemiology The disorder is panethnic but worldwide prevalence is not known. Prevalence at birth is estimated to be approximately 1:100,000 to 200,000 live births. [orpha.net]

Layout table for study information Study Type : Observational Estimated Enrollment : 1000 participants Observational Model: Cohort Time Perspective: Prospective Official Title: Biomarker for Gangliosidosis: BioGM1 / BioGM2 AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL [clinicaltrials.gov]

Further Reading Tay-Sachs Disease Symptoms Tay-Sachs Disease Pathophysiology Tay-Sachs Disease Diagnosis Tay-Sachs Disease Prevention Tay-Sachs Disease Society and Culture Tay-Sachs Disease Research This article is licensed under the Creative Commons [news-medical.net]

[…] history of ET and positive response to propranolol, [9] as well as cases of PWT and writers cramp in the same patient described in the literature. [7] The clinical features noted in our patient at least make a strong argument for dystonia being the pathophysiological [movementdisorders.org]

Uyama E, Terasaki T, Owada M, Naito M, Araki S (1990) Three siblings with type 3 GM1-gangliosidosis: pathophysiology of dystonia and MRI findings (in Japanese). Clin Neurol 30:818–827 Google Scholar 18. [link.springer.com]

Review GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies Andrés Felipe Leal et al. Int J Mol Sci. 2020. [pubmed.ncbi.nlm.nih.gov]

Primary prevention is the most effective intervention since no effective therapy is currently available. [ncbi.nlm.nih.gov]

About LYS-GM101 LYS-GM101 is designed to replace the defective gene in the cells of GM1 patients, which will allow for the production of the functional enzyme and prevent the progressive nature of the neurological damage caused by GM1. [raredr.com]