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Disease Profile

Neonatal adrenoleukodystrophy

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.


US Estimated

Europe Estimated

Age of onset






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


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.


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.


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


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.


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.


Not applicable


Other names (AKA)

Adrenoleukodystrophy autosomal neonatal form; NALD


Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases;


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

Orpha Number: 44

A variant of intermediate severity of the PBD-Zellweger syndrome spectrum (PBD-ZSS) charcterized by hypotonia, leukodystrophy, and vision and sensorineural hearing deficiencies. Phenotypic overlap is seen between NALD and infantile Refsum disease (IRD).

The estimated birth prevalence for PBD-ZSS is 1/50,000 in North America and 1/500,000 in Japan. More than half of patients with PBD-ZSS have the NALD-IRD forms.

Clinical description
NALD has an onset at birth or early infancy, but manifestations may be subtle enough that it is not diagnosed until late infancy or early childhood (or when a leukodystrophy develops). It is characterized by hypotonia, seizures, diffuse encephalopathy, sensorineural hearing loss, peripheral neuropathy, mild facial dysmorphism (hypertelorism and a flat midface), failure to thrive and severely delayed psychomotor development. Eye findings include chorioretinopathy, optic nerve dysplasia and cataracts. Hepatic dysfunction is first displayed in infants with jaundice and later in some with episodes of intracranial bleeding due to vitamin K-responsive coagulopathy. Adrenal insufficiency and renal calcium oxalate stones can present in older children. Vision and hearing dysfunction are progressive and result in blindness and deafness. Osteoporosis and fractures can occur in patients who are less mobile. Neurological regression reflects a leukodystrophy, leading to the loss of previously acquired skills, dementia and ultimately death.

PBD-ZSS is caused by mutations in one of 13 PEX genes encoding peroxins. Mutations in these genes lead to abnormal peroxisome biogenesis.

Diagnostic methods
NALD is suspected on physical examination and confirmed with biochemical evaluation. Plasma very-long-chain fatty acid (VLCFA) levels indicate defects in peroxisomal fatty acid metabolism with elevated plasma concentrations of C26:0 and C26:1 and elevated ratios of C24/C22 and C26/C22. Erythrocyte membrane concentrations of plasmalogens C16 and C18 are reduced. Plasma pipecolic acid levels and bile acid intermediates (THCH and DHCA) are increased. Sequence analysis of the 13 PEX genes can be performed. MRI can be used to identify leukodystrophy, neuronal migration defects or other brain malformations.

Differential diagnosis
The main differential diagnoses include Usher syndrome I and II, other PBD-ZSS disorders (see these terms), single enzyme defects in peroxisome fatty acid beta-oxidation, and disorders that feature severe hypotonia, neonatal seizures, liver dysfunction or leukodystrophy. X-linked adrenoleukodystrophy (see this term) should not be confused with NALD.

Antenatal diagnosis
Prenatal screening of cultured amniocytes and chorionic villus sampling for VLCFA and plasmalogen synthesis is possible. If both disease causing alleles in parents have been identified, prenatal diagnosis can be performed as well as preimplantation genetic diagnosis.

Genetic counseling
NALD is inherited in an autosomal recessive manner so genetic counseling is possible.

Management and treatment
There is no cure for NALD and treatment is symptomatic. Cataracts should be removed in early infancy and glasses used to improve vision. Hearing aids are provided to those with hearing impairment, and cochlear implants considered when hearing loss is profound. Hepatic coagulopathy can be treated with vitamin K supplementation and liver function may improve with primary bile acid therapy. A gastrostomy tube may be necessary to allow for adequate calorie intake. Foods rich in phytanic acid (such as cow's milk) should be restricted. Docosahexanoic acid can be provided. Standard epileptic drugs are used for seizures. Lifelong follow up is needed to monitor changes in hearing, vision and liver function.

Prognosis is poor with most patients dying in infancy and early childhood. Some have lived until their teenage years.

Visit the Orphanet disease page for more resources.


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:
80%-99% of people have these symptoms
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth

[ more ]

Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

Abnormality of the liver
Abnormal liver
Liver abnormality

[ more ]

Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

Long, narrow head
Tall and narrow skull

[ more ]

EEG abnormality
High forehead
Increased reflexes
Low-set, posteriorly rotated ears
Muscular hypotonia
Low or weak muscle tone
Involuntary, rapid, rhythmic eye movements
Optic atrophy
Primary adrenal insufficiency
Sensorineural hearing impairment
Severe global developmental delay
Short stature
Decreased body height
Small stature

[ more ]

Squint eyes

[ more ]

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 ]

30%-79% of people have these symptoms
Abnormality of neuronal migration
Abnormality of retinal pigmentation
Bilateral single transverse palmar creases
Clouding of the lens of the eye
Cloudy lens

[ more ]

Increased size of skull
Large head
Large head circumference

[ more ]

Drooping upper eyelid
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

Wide anterior fontanel
Wider-than-typical soft spot of skull
Percent of people who have these symptoms is not available through HPO
Abnormal facial shape
Unusual facial appearance
Adrenal insufficiency
Autosomal recessive inheritance
Elevated circulating long chain fatty acid concentration
Eye folds
Prominent eye folds

[ more ]

Inward turning cross eyed
Frontal bossing
High palate
Elevated palate
Increased palatal height

[ more ]

High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Low-set ears
Low set ears
Lowset ears

[ more ]

Polar cataract
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]



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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Neonatal adrenoleukodystrophy. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • 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 Neonatal adrenoleukodystrophy. Click on the link to view a sample search on this topic.