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Disease Profile

Pseudoneonatal adrenoleukodystrophy

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

Neonatal

ICD-10

E71.3

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)

Peroxisomal Acyl-CoA oxidase deficiency; Straight-chain Acyl-CoA oxidase deficiency; Pseudo-neonatal adrenoleukodystrophy;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

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

Orpha Number: 2971

Definition
Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.

Epidemiology
Acyl-CoA oxidase deficiency is a rare disease with only 30-40 patients identified world-wide so far.

Clinical description
The disease manifests in the neonatal period with hypotonia (92%) and seizures (91%) as dominant features. Facial dysmorphism (50%) with hypertelorism, epicanthus, low nasal bridge, and low-set ears may be present. Some children have polydactyly and hepatomegaly. Psychomotor development is delayed, but children are usually able to walk and say a few words. However, neurological regression occurs usually at the age of 1-3 years (mean age: 28 months). Hypotonia is replaced by hypertonia with hyperreflexia. Epilepsy may become more severe and sensorineural hearing loss may appear. Strabismus, nystagmus, and optic atrophy can also occur.

Etiology
Peroxisomal acyl-CoA oxidase deficiency is caused by mutations in the ACOX1 gene (17q25.1) encoding peroxisomal straight-chain acyl-CoA oxidase.

Diagnostic methods
Diagnosis is based on laboratory studies revealing increased serum very-long chain fatty acids (VLCFA) and markedly reduced acyl-CoA oxidase activity in fibroblasts. MRI examination of the brain shows abnormal white matter signals. Diagnosis can be confirmed by the presence of mutations in the ACOX1 gene.

Differential diagnosis
Differential diagnoses include Usher syndrome (see this term) and all causes of neonatal hypotonia. The other peroxisomal disorders should also be discarded, especially neonatal adrenoleukodystrophy (see this term), which presents similar clinical manifestations.

Antenatal diagnosis
Antenatal diagnosis is possible through biochemical and/or molecular analysis of amniocytes or chorionic villus cells.

Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to the families of patients.

Management and treatment
No specific treatment is available. Multidisciplinary supportive care should be offered.

Prognosis
Prognosis is unfavorable; death usually occurs at around 5 years from respiratory issues.

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
Abnormal nervous system morphology
Abnormal shape of nervous system
0012639
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Abnormality of visual evoked potentials
0000649
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
EEG abnormality
0002353
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Global developmental delay
0001263
Hyperreflexia
Increased reflexes
0001347
Hypodontia
Failure of development of between one and six teeth
0000668
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Muscular hypotonia
Low or weak muscle tone
0001252
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Seizure
0001250
Sensorineural hearing impairment
0000407
30%-79% of people have these symptoms
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Hepatomegaly
Enlarged liver
0002240
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Respiratory insufficiency
Respiratory impairment
0002093
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
5%-29% of people have these symptoms
Hand polydactyly
Extra finger
0001161
Hypertonia
0001276
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Babinski sign
0003487
Bilateral sensorineural hearing impairment
0008619
Brachycephaly
Short and broad skull
0000248
CNS demyelination
0007305
Decreased lightand dark-adapted electroretinogram amplitude
0000654
Diffuse hepatic steatosis
0006555
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Dystonia
0001332
Elevated hepatic transaminase
High liver enzymes
0002910
Frontal bossing
0002007
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Inverted nipples
0003186
Irritability
Irritable
0000737
Leukodystrophy
0002415
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
No social interaction
0008763
Pigmentary retinopathy
0000580
Rod-cone dystrophy
0000510
Severe global developmental delay
0011344
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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

      Organizations Providing General Support

        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.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Pseudoneonatal adrenoleukodystrophy. This website is maintained by the National Library of Medicine.

          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 Pseudoneonatal adrenoleukodystrophy. Click on the link to view a sample search on this topic.