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Disease Profile

Infantile neuronal ceroid lipofuscinosis

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.

Unknown

Age of onset

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ICD-10

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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)

Lipofuscin storage disease; Hagberg-Santavuori disease; INCL;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 79263

Definition
Infantile neuronal ceroid lipofuscinosis (INCL) is a form of neuronal ceroid lipofuscinosis (NCL; see this term) characterized by onset during the second half of the first year of life and rapid mental and motor deterioration leading to loss of all psychomotor abilities.

Epidemiology
Infantile NCL occurs worldwide but is most common in Finland with a prevalence of around 1/190,000 and incidence of 1/20,000 live births. The disorder is less frequent in other Scandinavian countries with a prevalence of below 1/1,000,000 in Sweden and Norway.

Clinical description
After an initial period of normal development, the disorder manifests after six months of age when mental development reaches a plateau and then starts to deteriorate, accompanied by motor dysfunction. The deterioration of mental abilities is accompanied by seizures, spasticity and loss of vision. Brain atrophy results in slower than normal growth of the head circumference and microcephaly. Stiffness and irritability may also be noted. Psychomotor abilities deteriorate rapidly and children fail to thrive leading to a vegetative state within several months.

Etiology
INCL is inherited in an autosomal recessive manner and is caused by mutations in the PPT1 gene (designated CLN1; 1p32) encoding the lysosomal enzyme palmitoylprotein thioesterase 1.

Diagnostic methods
Diagnosis is based on clinical findings from neurologic and ophthalmologic examinations and development assessments, and measurement of activity of palmitoyl-protein thioesterase 1 in leukocytes, dry blood samples or cultured skin fibroblast cells. The diagnosis can be confirmed by molecular analysis. Pathologic studies reveal the presence of autofluorescent lysosomal granular osmophilic deposits (GRODs) with characteristic accumulation of saposins A and D.

Differential diagnosis
The differential diagnosis should include other early-onset progressive neurologic diseases, including infantile Krabbe disease, early-stage Rett syndrome and gangliosidosis (see these terms).

Antenatal diagnosis
Prenatal diagnosis is possible on the basis of enzymatic analysis or molecular genetic testing if the mutation in the family has already been identified.

Genetic counseling
Genetic counseling should be provided to affected families.

Management and treatment
There is no curative treatment. Management consists of palliative care including administration of anticonvulsive drugs and treatment of severe spasticity with muscular relaxants. Oral opiates or fentanyl-containing plasters can be helpful for management of painful spastic crises occurring later in the disease course. Stem cell therapy may provide an alternative treatment for INCL in the future.

Prognosis
The prognosis is severe but life expectancy is variable, depending on the use of supportive measures such as gastrostomy feeding.

Visit the Orphanet disease page for more resources.

Symptoms

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
Abnormal electroretinogram
0000512
Abnormality of visual evoked potentials
0000649
Ataxia
0001251
Blindness
0000618
Cerebral atrophy
Degeneration of cerebrum
0002059
EEG abnormality
0002353
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Irritability
Irritable
0000737
Macular dystrophy
0007754
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Motor deterioration
Progressive degeneration of movement
0002333
Myoclonus
0001336
Optic atrophy
0000648
Seizure
0001250
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior

[ more ]

0000733
Visual loss
Loss of vision
Vision loss

[ more ]

0000572

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.
  • 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 Infantile neuronal ceroid lipofuscinosis. Click on the link to view a sample search on this topic.