Tay Sachs Disease – 9 Interesting Facts

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Interesting Facts of Tay Sachs Disease

  1. Tay Sachs disease is an autosomal recessive lipid storage disorder caused by HEXA gene mutations and characterized by progressive neurodegeneration 1
  2. Carrier frequency of mutations involved in Tay Sachs disease is highest among individuals of Ashkenazi Jewish and Central-eastern European descent 2
  3. Classified into 3 forms depending on timing of symptom appearance: infantile (most common), juvenile-onset, and adult-onset 1
  4. Classic infantile variant is characterized by rapid progression of global cognitive and neuromuscular degeneration, progressive blindness, and a macular cherry-red spot on physical examination; juvenile- and adult-onset variants are typically associated with slower disease progression 1
  5. Diagnosis is suspected based on clinical findings and confirmed by enzyme assays showing low to absent levels of hexosaminidase A in an individual with normal to elevated β-hexosaminidase B levels
  6. No cure is currently available; treatment consists of supportive care to improve patient’s quality of life
  7. Severe complications include seizures, aspiration pneumonia, respiratory arrest, bronchopneumonia, and early death
  8. Patients with infantile- and juvenile-onset variants typically die by ages 2 to 4 years and late teens, respectively; adult-onset variant is associated with long-term survival into the fifth or sixth decade of life or later
  9. Carrier and prenatal testing are critical in reducing births of affected individuals; screening for HEXA gene mutations is recommended before childbearing in individuals at high risk (eg, patients with a family history of Tay-Sachs, and individuals of Ashkenazi Jewish, French Canadian, or Cajun descent)

Synonyms of Tay Sachs Disease

  1. B Variant GM2-Gangliosidosis
  2. GM2 Gangliosidosis, Type 1
  3. Hexoaminidase Alpha-Subunit Deficiency (Variant B)
  4. Hexosaminidase A deficiency
  5. HEXA deficiency
  6. Sphingolipidosis, Tay-Sachs
  7. TSD

Subdivisions of Tay Sachs Disease

  • Infantile Tay-Sachs Disease
  • Juvenile (Subacute) Tay-Sachs Disease
  • Late-Onset Tay-Sachs Disease

Pitfalls

  • Some individuals suspected of having the Tay Sachs Disease show hexosaminidase A activity level within the reference range, measured by enzyme assay using 4-methylumbelliferylβ-N-acetylglucosamine 3
    • In such cases and when clinical findings are highly indicative of the disease, reexamine using sulfated form of 4-methylumbelliferyl-β-N-acetylglucosamine as a substrate
    • DNA mutational analysis is also definitive
  • Late-onset disease is infrequent and diagnosis is often delayed or missed altogether because of the late development or slow progression of significant clinical problems 4
    • Seen more frequently with non-Jewish individuals or in the absence of a family history 5
  • Approximately 30% of non-Jewish individuals identified as carriers by enzyme assay are characterized by pseudodeficiency alleles. Perform DNA mutational analysis to identify false-positive cases 3
    • Recognized pseudodeficiency alleles are p.Arg247Trp and p.Arg249Trp 1

Terminology

Clinical Clarification

  • Tay Sachs disease is an autosomal recessive lipid storage disorder (sphingolipidosis) resulting in progressive cognitive and neuromuscular degeneration 1
    • Most common infantile variant results in blindness, characteristic macular cherry-red spot, and death by age 4 years
  • Primarily affects patients of Eastern European Ashkenazi Jewish descent 1
  • Also called hexosaminidase A deficiency or GM₂ gangliosidosis 6
  • Tay Sachs disease is a rare inherited disorder that affects infants and young children. It causes slow development and problems with movement. The condition gradually gets worse.

Classification

  • Infantile, classic (most common) 1
    • Neurodegeneration begins before birth
    • Characterized by rapid disease progression; death by age 4 years 1
    • Caused by no or extremely low hexosaminidase A activity (0%-5%) 1
  • Juvenile onset, subacute (rare)
    • Symptoms appear between age 2 and 10 years; death in late teens 1
    • Characterized by a slower progression and increased heterogeneity of disease as compared to infantile variant 1
      • In some cases may be aggressive, resulting in death in 2 to 4 years 1
    • Caused by a deficiency in hexosaminidase A enzyme activity (less than 15%) 1
  • Adult onset, chronic (rare) 4
    • Symptoms appear in late childhood, teens, or adulthood; death in the fifth to sixth decade of life 4
    • Characterized by heterogeneity in phenotype and slow progression of disease with long-term survival 4
    • Caused by a deficiency in hexosaminidase A enzyme activity (less than 15%) 1

What are the causes of Tay Sachs Disease?

Tay Sachs Disease is caused by a defective gene that has been inherited from both parents.

The gene causes a lack of the enzyme hexosaminidase A (Hex-A). Without Hex-A, a fatty substance called ganglioside builds up in nerve cells in the brain. This buildup gradually destroys the nerve cells.

People who have inherited the gene from only one parent will not have Tay Sachs disease, but they can pass the gene to their own children.

What increases the risk of Tay Sachs disease?

This condition is more likely to develop in children who have parents that carry the gene for Tay Sachs disease. People in certain groups are more likely to be carriers. These groups include:

  • Jewish people from eastern Europe (Ashkenazi Jews).
  • French Canadians who live near the Saint Lawrence River.
  • Cajun communities in Quebec and Louisiana.

Symptoms of Tay Sachs disease

Symptoms of Tay Sachs disease usually start at 3–6 months of age.

Very Common Symptoms and Signs of Tay Sachs Disease (80%-98%)

  • Abnormality of movement 
  • Ataxia 
  • Blindness 
  • Cherry red spot of the macula 
  • Developmental regression 
  • EEG abnormality 
  • Global developmental delay 
  • Hearing impairment 
  • Hemiplegia/hemiparesis 
  • Hyperreflexia 
  • Increased muscle lipid content 
  • Intellectual disability, progressive 
  • Macrocephaly 
  • Psychomotor deterioration 
  • Seizures 
  • Visual impairment 

Common Symptoms and Signs of Tay Sachs Disease (30%-79%)

  • Hepatomegaly 
  • Muscular hypotonia 
  • Myotonia 
  • Optic atrophy 
  • Recurrent respiratory infections 
  • Spasticity 
  • Splenomegaly 

Early symptoms of Tay Sachs disease

  • A strong reflex when the child is startled.
  • Floppiness.
  • Irritability.
  • Lack of activity.
  • Loss of skills that the child had already acquired, such as rolling over.

Later symptoms of Tay Sachs disease

  • Low muscle tone. This can make the child unable to hold up his or her head.
  • Failure to develop physical and mental abilities.
  • Loss of physical and mental abilities that the child had already developed.
  • Seizures. Over time, these happen more often and get harder to control.
  • Blindness.
  • Problems with breathing, hearing, and swallowing.
  • Weakness.
  • Decreased movement.
  • Paralysis.
  • Lack of response to the environment.

History

  • Occasionally, family history of Tay Sachs disease (infantile and juvenile-onset variants)
  • History of recurring pneumonia
  • Infantile variant
    • Presents with slowing and regression of developmental milestones, progressive hypotonia followed by the development of spasticity, progressive cognitive decline, and blindness
    • Birth
      • Infants appear physically normal 7 8
        • Normal motor development in the first couple of months of life
    • By age 3 to 6 months 1
      • Slowing of developmental milestones 8
        • Hyperacusis
        • Fasciculations
        • Decreased attentiveness
        • Mild motor weakness and hypotonia
    • By age 6 to 10 months 1 8
      • Loss of previously acquired motor skills and delay in developmental milestones
        • Hypotonia (58% of patients)
        • Inability to sit or roll over
        • Decrease in visual attention and eye movements
    • By age 8 to 10 months 1
      • Deterioration in development
        • Mental status depression
        • Diminished voluntary movement
        • Worsening of visual attention
          • Inability to follow movements with eyes or clumsiness
    • By age 12 months 1 8
      • Progressive decline in mental status and loss of milestones
        • Lethargy
        • Seizures are common (39% of patients) and become more frequent and severe
    • During the second year and subsequently
      • Unexplained fevers
      • Difficulty in swallowing/feeding
      • Inability to handle secretions with drooling
      • Irregular or abnormal breathing patterns
      • Worsening of seizures
      • Progressive rigidity and spasticity
      • Obtundation
      • Vegetative state
  • Juvenile-onset variant 1
    • Presents with progressive cognitive decline, dystonia, blindness, increasing seizures, and spinocerebellar/motor neuron degeneration
    • Early symptoms (between age 2 and 10 years) 1
      • Ataxia and poor coordination
        • Dyspraxia with loss of balance
        • Difficulty with fine motor skills
      • Sphincter incontinence 3
      • Dysarthria 1
      • Dysphagia 3
      • Cognitive impairment
        • Memory impairment
        • Intellectual decline
        • Learning disability
      • Spasticity and seizures by age 10 years 1
    • Later symptoms (age 10-15 years) 1
      • Loss of vision
      • Dystonia
      • Decerebrate posture
      • Obtundation
      • Vegetative state
  • Adult-onset variant 1
    • Presents with progressive muscular weakness, fasciculations, dysarthria, cognitive dysfunction, and prominent psychiatric manifestations
    • Variable age of onset (late childhood or older) and variable disease progression 4
    • Early teenage years 5
      • Dysarthria that does not improve with therapy
      • Declining academic performance
    • Later adolescence 5
      • Muscle weakness and cramping develops
      • Fasciculations
    • Early 20s 5
      • Ataxic gait and high steppage
      • Psychiatric symptoms including anxiety, depression, and bipolar symptoms develop in approximately 40% of patients 2 5
      • Although vision is not impaired, saccadic pursuit is coarse 5
    • Later symptoms 5
      • Diminished fine motor skills of the neck, forearm, and hands evident
        • Tremor in outstretched arms, dysmetria, and ataxia
      • Atrophy of shoulder and leg muscles follow 5
        • Patient loses the ability to tandem walk
    • Patients older than 50 years 5
      • Painful edema in ankles and cool, purple feet
      • Urinary urgency and frequency

Physical examination

  • Infantile variant
    • Excessive startle reflex
    • Progressive macrocephaly and doll-like facial features develop by age 18 months 1
    • Ocular abnormalities
      • Cherry-red macular spot in the fovea centralis of the retina
        • Present in all patients with infantile form 1
      • Deterioration in vision progressing to blindness
        • Inability to focus and track objects
    • Progressive deterioration in:
      • Cognitive function
        • Deterioration in responsiveness
      • Motor function
        • Progressive change in tone
          • Initial hypotonia and loss of motor skills
          • Fasciculations
          • Progression to decerebrate body posture
            • Rigidity
            • Spasticity with hyperreflexia and clonus
    • Variable skin changes
      • Rubor, pallor, or cyanosis
    • Frequent and severe seizures
  • Juvenile-onset variant
    • Variable ocular abnormalities
      • Cherry-red spot may or may not be present
      • Optic atrophy
      • Retinitis pigmentosa
      • Blindness
    • Progressive deterioration in:
      • Cognitive function
        • Overall intellectual decline
        • Unresponsiveness
      • Motor function
        • Global decline in fine and gross motor skills
          • Progressive weakness and spasticity
      • Cerebellar function
        • Ataxia and poor coordination
  • Adult-onset variant
    • Extraocular movement dysfunction 9
      • Saccade abnormalities
    • Progressively worsening: 1
      • Cognitive dysfunction
        • Memory decline
        • Global intellectual ability defects
      • Motor weakness
        • Hypotonia
        • Fasciculations
        • Muscular atrophy
      • Cerebellar dysfunction
        • Dysmetria
        • Tremor
        • Ataxia
    • Altered mental status/psychiatric manifestations are prominent
      • Agitation
      • Delusion
      • Paranoia
      • Hallucination
      • Dementia
      • Acute hebephrenic schizophrenia episodes

Causes of Tay Sachs Disease

Causes

  • Cause is a mutation in the alpha subunit of the HEXA gene located on the long arm of chromosome 15 (15q23-q24) (OMIM# 272800) 10 3
    • Infantile
      • More than 90 different HEXA mutations are associated with this variant of the Tay Sachs Disease1
        • Homozygous null or compound heterozygous mutations in the α subunit of HEXA gene resulting in nearly complete loss of hexosaminidase A enzyme activity
        • Common mutations
          • pTyr427IlefsTer5
          • c.1421+1G>C
          • c.1073+G>A
    • Juvenile-onset
      • p.Arg178His mutation is most common 1
      • Compound heterozygous and homozygous mutations in the α subunit of HEXA gene are associated with this variant of the disease
        • Compound heterozygous mutations result in partial loss of hexosaminidase A enzyme activity
        • Homozygous mutations result in more hexosaminidase A activity than compound heterozygous mutations
    • Adult-onset
      • p.Gly269Ser and p.Gly250Asp mutations most common 1
      • Homozygous or compound heterozygous mutations
  • Abnormal gene product results in an absence or severe deficiency of hexosaminidase A, an enzyme that breaks down the fatty acid GM₂ ganglioside 7
    • Inadequacy of functional hexosaminidase A results in progressive accumulation of glycolipid GM₂ ganglioside (lipid) in neuronal lysosomes
    • Infantile variant is characterized by a loss of enzyme activity
    • Juvenile- and adult-onset variants are characterized by a deficiency in enzyme activity

Risk factors of Tay Sachs Disease

Age
  • Infantile
    • Tay Sachs Disease most commonly affects children aged 3 months to 4 years 1
    • Average age of onset is 5 months 7 8
  • Juvenile-onset
    • Tay Sachs Disease most commonly affects children aged 2 years to late teens 1
  • Adult-onset
    • Tay Sachs Disease affects a wide range of ages; begins in late childhood through the third or fourth decade of life 1 3
Genetics
  • Inheritance is autosomal recessive 10
Ethnicity/race
  • Central-eastern European or Ashkenazi Jewish descent
    • Tay Sachs Disease is 100 times more prevalent in Jewish than non-Jewish individuals 2
    • Carrier frequency for HEXA mutations is 1 in every 29 Ashkenazi Jews and 1 in every 110 Moroccan Jews 11
  • Other populations with high carrier rate
    • Old Order Amish in Pennsylvania
      • Carrier frequency similar or higher than that of Ashkenazi Jews 1
    • French Canadians living in Quebec, east of the Saint Lawrence River valley
    • Cajun people from Louisiana
    • Irish 12
  • Sephardic Jews and non-Jews
    • Carrier frequency of 1 in every 250 to 300 1
    • Pseudodeficiency mutations comprise approximately 30% of the mutations identified in non-Jewish individuals 13

How is Tay Sachs disease diagnosed?

Tay Sachs disease is diagnosed with a physical exam and a blood test. The blood test may check Hex-A levels or identify the abnormal gene that causes the disease.

An eye exam may also be done to check for a red spot in the back of the eye. This spot is found in most children who have Tay Sachs disease.

Tay Sachs Disease can also be diagnosed In unborn babies by removing a sample of fluid from the womb.

Primary diagnostic tools

  • History and physical examination 1 3
    • Perform definitive diagnostic laboratory and molecular testing if findings of progressive loss of developmental milestones, hyperactive startle reflex, and cherry-red macular spot
    • Involve developmental genetics for any child with declining muscle tone and regression of developmental milestones for assistance with a formal diagnosis
  • Hexosaminidase assay is the first step to diagnose Tay-Sachs 1
    • Diagnosis is based on the identification of low to absent levels of hexosaminidase A in an individual with normal to elevated β-hexosaminidase B levels 1
  • Genetic analysis is then performed to confirm hexosaminidase A mutations; this step is instrumental in ruling out false-positive result of enzyme assay caused by pseudodeficiency alleles and to allow for genetic counseling of patient’s family members 1 3
  • Late-onset disease is uncommon and diagnosis is often delayed or missed altogether because of the late development or slow progression of significant clinical problems 4
    • Seen more frequently with non-Jewish people or in the absence of a family history 5

Laboratory tests for Tay Sachs Disease

  • Blood test 1
    • Hexosaminidase enzyme assay 1
      • To measure the activity levels of hexosaminidase A and B in the serum
        • Findings consistent with Tay-Sachs disease
          • Low to absent levels of hexosaminidase A in an individual with normal to elevated β-hexosaminidase B levels
            • Infantile variant
              • No or low (0%-5%) hexosaminidase A activity 1
            • Juvenile- and adult-onset variants
              • Low hexosaminidase A activity (less than 15%) 1
          • Findings consistent with carriers for Tay-Sachs disease
            • Enzyme activity in carriers is less than 52%; noncarriers enzyme activity is greater than 60% 12
            • Enzyme activity between 52% and 60% is inconclusive 12
          • Sensitivity of hexosaminidase enzyme assay is 98% 12
        • Test limitations
          • Exclude false-negative hexosaminidase A activity in patients who have clinical findings highly suggestive of disease
            • If hexosaminidase A enzyme test shows hexosaminidase A activity level within the reference range in patients with suspicious clinical findings, reexamine using synthetic sulfated form of 4-methylumbelliferyl-β-N-acetylglucosamine (a specific substrate of hexosaminidase A) 3
          • False-negative results can occur on serum samples in pregnant patients and in patients taking oral contraceptives
            • Use leukocytes for testing in pregnant patients or patients taking oral contraceptives to diminish false-negative results
          • False-positive results can occur from biochemical testing in patients with pseudodeficiency alleles (alleles that result in lower levels of hexosaminidase A activity but not disease) 3
            • Definitive DNA testing will exclude false-positive screening results by hexosaminidase A biochemical enzyme assay
            • Recognized pseudodeficiency alleles are p.Arg247Trp and p.Arg249Trp 1
    • HEXA mutational analysis 1
      • To identify causative mutations in HEXA gene in DNA isolated from serum or leukocytes as definitive diagnosis following hexosaminidase assay
        • Acute infantile variant: pTyr427IlefsTer5, c.1421+1G>C, and c.1073+G>A
        • Juvenile-onset variant: p.Arg178His (juvenile form)
        • Adult-onset variant: p.Gly269Ser and p.Gly250Asp

Differential Diagnosis

Most common

  • Sandhoff disease 14
    • Rare hereditary disorder of lipid storage caused by deficiency in both β-hexosaminidase A and β-hexosaminidase B activities and characterized by progressive neurodegeneration; most commonly occurs in infants, with death by early childhood
    • Clinical manifestations are similar to Tay-Sachs as most patients present in infancy with hyperacusis, neurologic regression, and cherry-red macula; rarely observed in Jewish patients
    • Distinguish by the presence of organomegaly, skeletal abnormalities and oligosacchariduria; hexosaminidase B activity is absent
  • Niemann-Pick disease type A 15
    • Hereditary metabolic disorder affecting young children with death by early childhood
    • Some clinical manifestations are similar to Tay-Sachs as most patients present in infancy with failure to thrive, recurrent lung infections, cherry-red macula, psychomotor regression, and progressive loss of developmental milestones
    • Distinguishing clinical feature of Niemann-Pick disease type A is prominent hepatosplenomegaly; hexosaminidase levels are within reference range
    • Definitive testing by enzyme assays shows deficiency in acid sphingomyelinase activity
  • Neuronal ceroid-lipofuscinosis (infantile, late infantile, and juvenile types)
    • Group of progressive neurodegenerative disorders that affect infants and children with variable progression of disease; patients with early infantile form do not live past childhood, those with late infantile form do not live past teenage years, and those with juvenile form do not live past third decade of life 16
    • Clinical manifestations are similar to Tay-Sachs as patients present with psychomotor retardation, seizures, ataxia, hypotonia, visual impairment, spasticity, and neurologic impairment
    • Distinguish from Tay-Sachs by hexosaminidase levels within the reference range
    • Definitive testing by enzyme assays showing deficiency in 1 of the following enzymes: palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1, or cathepsin D 16
  • Kugelberg-Welander syndrome
    • Rare hereditary neuromuscular disorder that usually manifests during the first and second decades of life 17
    • Some clinical manifestations are similar to Tay-Sachs, such as wasting and weakness of arm and leg muscles
    • Distinguishing clinical feature of Kugelberg-Welander syndrome is scoliosis; hexosaminidase levels are within reference range
    • Distinguish by molecular testing identifying a mutation in SMN gene
  • Amyotrophic lateral sclerosis
    • Progressive motor neuron disease that most commonly affects adults (median age of disease onset is 46 to 56 years); death usually results from compromised respiratory muscles within approximately 3 years of disease onset 18
    • Clinical manifestations are similar to Tay-Sachs as patients present with fasciculations, spasticity, muscle weakness and wasting, dysphagia, and dysarthria
    • Differentiate from Tay-Sachs by lack of cognitive decline and hexosaminidase levels within the reference range
    • No single test is diagnostic of amyotrophic lateral sclerosis 18
      • Presence of upper and lower motor neuron impairment is highly suggestive of the disease
      • A series of diagnostic testing (eg, electromyography, nerve conduction study, MRI) should be performed to exclude the possibility of other similar conditions
  • Leigh disease (subacute necrotizing encephalomyelopathy)
    • Disorder of mitochondrial energy metabolism characterized by rapid, progressive encephalopathy in young children with death in infancy; lactic acidosis is a prominent feature in infants with Leigh disease, which leads to significant respiratory and renal dysfunction 19
    • Clinical manifestations are similar to Tay-Sachs as patients present in infancy with developmental delay, psychomotor regression, hypotonia, seizures, dementia, and ophthalmoplegia/nystagmus
    • Children with Leigh disease typically differ in presentation with pronounced irritability (almost continuous crying), vomiting, and optic atrophy (no cherry-red spot)
    • Distinguish by hexosaminidase A enzyme activity level within the reference range or absence of HEXA mutations

How is Tay Sachs Disease treated?

At this time, there is no cure for Tay Sachs Disease. The goal of treatment is to keep the child as comfortable as possible.

This may require a team of health care providers. Sometimes, medicines are given to prevent seizures.

Goals

  • Supportive care to improve patient’s quality of life
  • Maintain nutrition and hydration 3
  • Prevent infection 3
  • Control seizures 3

Disposition

Admission criteria

Disease complications requiring hospital admission include:

  • Aspiration pneumonia
  • Status epilepticus
  • Bowel obstruction from severe constipation
Criteria for ICU admission
  • Patients with aspiration pneumonia requiring ICU ventilator support

Recommendations for specialist referral

  • Following initial diagnosis, patients are typically managed by a team of consultants 1
    • Ophthalmologist to evaluate extent of the disease at time of diagnosis
    • Pulmonologist to assist with frequent pneumonia management and optimize respiratory care
    • Pediatric neurologist to manage seizures 1
    • Gastroenterologist to manage gastrostomy tubes, severe constipation, and dysphagia

Treatment Options

There is no cure for Tay Sachs Disease; treatment is focused on controlling seizures and providing supportive care 1 3

  • Antiepileptic drugs for patients with seizures
  • Supportive care is individualized based on patient symptoms and includes:
    • Physical therapy
    • Chest physiotherapy
    • Maintenance of proper nutrition and hydration

Drug therapy for Tay Sachs Disease

  • Antiepileptic drugs 1
    • Appropriate type and dosage depends on the individual type and severity of the seizure present
      • Carbamazepine and propranolol 3 may be suggested for management of seizures in adults 3
      • Diazepam is suggested for management of seizures in infants 3

Nondrug and supportive care 3

  • Protect airway and provide respiratory support
    • Manage chest congestion with chest physiotherapy
    • Oxygen administration on an as needed basis
    • Tracheotomy tube when patient is at risk of aspiration
    • Assisted ventilatory support based on expected disease course and family preference
  • Proper nutrition and hydration
    • High-calorie diet with semisolid or pureed food 3
      • Administer via gastrostomy tube if necessary
    • Special techniques/strategies for nursing infant as facilitated by a lactation consultant 2 3
      • Help to close lips around nipple
      • Special feeding bottles designed for babies with cleft lip or palate
    • Percutaneous endoscopic gastrectomy when child is at risk of aspiration
  • Physical therapy to improve motor skills and decrease spasticity 3

Complications and Prognosis

Complications

  • Respiratory arrest leading to death
    • As a result of lung damage caused by repeated lung infections
  • Aspiration pneumonia
    • Caused by aspiration of oral secretions due to excessive saliva production and/or dysphagia
  • Bronchopneumonia is common in the infantile variant 1
  • Severe constipation resulting in bowel obstruction

Prognosis of Tay Sachs Disease

  • Tay Sachs Disease is universally fatal; there is no cure
    • Infantile variant
      • Life expectancy is between 2 and 4 years 1
      • Most common cause of death is bronchopneumonia 1
    • Juvenile-onset variant
      • Life expectancy is into the late teens 1
      • Most common cause of death is respiratory tract infection 3
    • Adult-onset variant
      • Not as lethal as infantile or juvenile-onset variants
      • Disease progression is slow with long-term survival into the fifth or sixth decade of life or later 4

Screening and Prevention

Screening of Tay Sachs Disease

At-risk populations

  • By definition, individuals are considered high-risk when they: 20
    • Are of Ashkenazi Jewish, French Canadian, or Cajun descent 20
    • Have a family history of Tay-Sachs disease 20
  • Carrier screening is recommended before pregnancy when: 20
    • Both members of a couple are considered high risk 20
      • Screen both partners simultaneously 20
    • 1 member of a couple is considered high risk 20
      • Screen high-risk partner 20
        • If high-risk partner is determined to be a carrier, screen other partner 20
  • If both members of a couple are carriers, genetic counseling should be provided, with regard to: 20
    • A 25% chance of having a child with the disease for each pregnancy 21 22
    • Availability of assisted reproductive therapy to avoid disease in future pregnancy 23

Screening tests

  • Carrier screening
    • Screening indications for specific patient populations
      • Screening for Tay-Sachs disease should be offered when considering pregnancy or during pregnancy if either member of a couple is of Ashkenazi Jewish, French Canadian, or Cajun descent; those with a family history of Tay-Sachs disease also should be offered screening 20
      • When 1 member of a couple is at high risk (Ashkenazi Jewish, French Canadian, or Cajun descent or has a family history of Tay-Sachs disease) but the other partner is not, the high-risk partner should be offered screening; if the high-risk partner is found to be a carrier, the other partner should also be offered screening 20
    • Testing options
      • DNA mutational analysis 20
      • Hexosaminidase enzymatic activity testing in serum or leukocytes 20
        • Use leukocyte testing if individual screened is pregnant or taking oral contraceptives 20
  • If both parents are carriers, consult a genetic counselor for help in deciding whether to have a fetus tested for Tay-Sachs 23
    • HEXA mutational analysis
      • Perform around 11th week of pregnancy 1 23
        • Obtain sample by chorionic villus sampling 1 23
      • Alternatively, perform around 16th week of pregnancy 1 23
        • Obtain sample by amniocentesis 1 23

Follow these instructions at home:

  • Work with all of your child’s health care providers to make a home care treatment plan.
  • Give over-the-counter and prescription medicines only as told by your child’s health care provider.
  • Make sure you:
    • Know how to keep your child’s airway clear. If you do not know how to do this, ask your child’s health care provider.
    • Know what to do if you can no longer care for your child at home.

Contact a health care provider if:

  • There is a change in your child’s mental status.
  • Your child has symptoms of an upper respiratory infection, such as a cough or a runny or stuffy nose.
  • Your child vomits.
  • Your child develops diarrhea.
  • Your child has seizures that last longer or happen more often than before.
  • Your child has pain or tenderness in any part of his or her body.
  • Your child has a fever.

Get help right away if:

  • Your child is not responsive.
  • Your child has a seizure that lasts longer than 15 minutes and cannot be controlled by seizure medicine.
  • Your child who is younger than 3 months has a temperature of 100°F (38°C) or higher.
  • Your child has fast or difficult breathing.
  • Your child’s pain medicine is not helping.
  • You see a blue color around your child’s mouth or fingertips.

Prevention of Tay Sachs Disease

  • Offer genetic counseling and prenatal diagnosis to couples in which both partners are carriers of Tay-Sachs mutation 20
    • Reproductive options include either of the following: 12
      • In vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic diagnosis
      • Use of a donor gamete to achieve healthy embryo 12
  • No prevention is available for individuals born with homozygous or compound heterozygous HEXA mutations

Sources

Kaback MM et al: Hexosaminidase A deficiency. In: Pagon RA et al, ed. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993-2016

Cross Reference

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