Rare Nephrology News

Disease Profile

Juvenile amyotrophic lateral sclerosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

G12.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Amyotrophic lateral sclerosis, juvenile; JALS; Juvenile Charcot disease;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Juvenile amyotrophic lateral sclerosis (JALS) is a rare motor neuron disease characterized by progressive degeneration of upper and lower motor neurons. Motor neurons are nerve cells that control voluntary muscle activity.[1] Symptoms of JALS typically begin before age 25, but often in early childhood.[1][2] Symptoms include facial spasticity, dysarthria, and a spastic gait (manner of walking). Some people have uncontrolled laughter and weeping, mild wasting of the legs and hands, bladder dysfunction, and/or sensory disturbances.[1] The disease is usually slowly progressive but rate of progression varies.[2] People with JALS may become unable to move by age 12 to age 50.[1]

JALS includes several subtypes, distinguished by the specific variations (mutations) in any of several genes, including:[1][2]

There are some reports of JALS caused by mutations in the UBQLN2 (related to ALS15), FUS (related to ALS6) and TARDBP (related to ALS10) genes.[1][2][3][4]

Mutations may be inherited from a parent or may occur for the first time in a person with the disease.[2] Inheritance may be autosomal recessive or autosomal dominant depending on the gene involved.[1][2]

There is no specific treatment for JALS. Management generally involves physical and occupational therapy to promote mobility and independence.[1]

Symptoms

Signs and symptoms of juvenile amyotrophic lateral sclerosis (JALS) begin before age 25 (which defines the juvenile form). All people with JALS eventually develop symptoms of both upper and lower motor dysfunction, but the symptoms, rate of progression, and severity varies from person to person.[5]

Signs of upper motor neuron dysfunction include the Babinski sign, muscle spasms, and overactive reflexes (hyperreflexia). Lower motor neuron signs include muscle wasting (atrophy), weakness, and muscle twitches.[5] Facial spasticity, slurred speech (dysarthria), and a spastic gait are common. Some people with JALS have uncontrolled laughter or crying, bladder dysfunction, and/or sensory disturbances.[1] Cognitive function is not affected.[5] The disease is usually slowly progressive but the rate of progression varies.[2] People with JALS may become unable to move by age 12 to age 50.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Amyotrophic lateral sclerosis
0007354
Distal amyotrophy
Distal muscle wasting
0003693
Lower limb spasticity
0002061
Upper limb spasticity
Uncontrollable movement in upper arms
0006986
30%-79% of people have these symptoms
Arm dystonia
0031960
Brisk reflexes
0001348
Bulbar signs
0002483
CNS hypomyelination
0003429
Contractures of the joints of the lower limbs
0005750
Contractures of the joints of the upper limbs
0100360
Delayed ability to walk
0031936
Difficulty walking
Difficulty in walking
0002355
Distal muscle weakness
Weakness of outermost muscles
0002460
Inability to walk
0002540
Muscle fiber atrophy
Muscle fiber degeneration
0100295
Spastic diplegia
0001264
5%-29% of people have these symptoms
Abnormal cerebellum morphology
Abnormality of the cerebellum
Cerebellar abnormalities
Cerebellar abnormality
Cerebellar anomaly

[ more ]

0001317
Anarthria
Loss of articulate speech
0002425
Ataxia
0001251
Axial dystonia
0002530
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Cachexia
Wasting syndrome
0004326
Chorea
0002072
Clonus
0002169
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Gastrostomy tube feeding in infancy
0011471
Global developmental delay
0001263
Head titubation
0002599
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Neck flexor weakness
Neck flexion weakness
0003722
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Opisthotonus
0002179
Oromandibular dystonia
0012048
Parkinsonism
0001300
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Retrocollis
0002544
Scoliosis
0002650
Supranuclear gaze palsy
0000605
Toe walking
Toe-walking
0040083
Urinary incontinence
Loss of bladder control
0000020

Cause

Juvenile amyotrophic lateral sclerosis (JALS) can be caused by mutations in any of several genes including ALS2, SIGMAR1, SPG11, SETX, SOD1, UBQLN2, FUS, and TARDBP.[1][2] Mutations bay be inherited from a parent or occur for the first time in a person with the disease.[2] Inheritance may be autosomal recessive or autosomal dominant depending on the gene involved.[1][2]

Genes responsible for amyotrophic lateral sclerosis (ALS) are important for normal functioning of motor neurons and other cells. It isn't always clear how mutations in these genes cause ALS.[6]

Treatment

There is no specific treatment for juvenile amyotrophic lateral sclerosis (JALS). Management generally involves strategies to to relieve symptoms and to promote mobility and independence.[1] Medications may include those for specific symptoms such as fatigue and muscle cramping. Physical therapy and special equipment can be helpful. Multidisciplinary teams of various health care professionals can help to develop personalized treatment plans.[7]

 

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    In-Depth Information

    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
    • PubMed is a searchable database of medical literature and lists journal articles that discuss Juvenile amyotrophic lateral sclerosis. Click on the link to view a sample search on this topic.

      References

      1. Bertini E. Juvenile amyotrophic lateral sclerosis. Orphanet. February, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=300605.
      2. Liu ZJ, Lin HX, Liu GL, Tao QQ, Ni W, Xiao BG, Wu ZY. The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis. Clin Genet. April, 2017; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/28429524.
      3. Zou ZY, Cui LY, Sun Q, Li XG, Liu MS, Xu Y, Zhou Y & Yang XZ. De novo FUS gene mutations are associated with juvenile-onset sporadic amyotrophic lateral sclerosis in China. Neurobiol Aging. April, 2013; 34(4):1312.e1-8. https://www.ncbi.nlm.nih.gov/pubmed/23046859.
      4. Teyssou E, Chartier L, Amador MD & cols. Novel UBQLN2 mutations linked to amyotrophic lateral sclerosis and atypical hereditary spastic paraplegia phenotype through defective HSP70-mediated proteolysis. Neurobiol Aging. October, 2017; 58:239.e11-239.e20. https://www.ncbi.nlm.nih.gov/pubmed/28716533.
      5. Orban P, Devon RS, Hayden MR, Leavitt BR. Juvenile Amyotrophic Lateral Sclerosis. Handbook of Clinical Neurology. Elsevier; 2007; 82(3):301-312. https://www.ncbi.nlm.nih.gov/pubmed/18808900.
      6. Amyotrophic Lateral Sclerosis. Genetics Home Reference. March, 2016; https://ghr.nlm.nih.gov/condition=amyotrophiclateralsclerosis.
      7. Kinsley L, Siddique T. Amyotrophic Lateral Sclerosis Overview. GeneReviews. February 12, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1450/.

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