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PubMed This is a summary of 50 peer-reviewed journal articles Updated
Medical Genetics

Understanding Infantile Refsum Disease and Zellweger Spectrum Disorders

At a Glance

Infantile Refsum Disease (IRD) is a rare, inherited Zellweger Spectrum Disorder caused by PEX gene mutations. It affects how cells process certain fats. As a milder form on the spectrum, children with IRD often live into late childhood or adulthood.

Receiving a diagnosis of Infantile Refsum Disease (IRD) can feel overwhelming, especially when navigating a maze of medical terms like “Zellweger Spectrum” and “Peroxisomal Disorders.” It is important to know that you are not alone on this journey. IRD is part of a group of rare, inherited conditions where the body has difficulty processing certain fats and acids due to a shortage of peroxisomes—the tiny “recycling centers” within every cell [1][2].

You can find more detailed information in the following sections:

01

Symptoms and the Biology of Infantile Refsum Disease

Learn about the symptoms and biology of Infantile Refsum Disease (IRD). Understand how PEX gene mutations affect your child's vision, hearing, and liver.

02

Getting the Right Diagnosis: Blood Tests and Genetics in IRD

Learn how Infantile Refsum Disease (IRD) is diagnosed. Understand normal VLCFA results, C26:0-lysoPC blood tests, and how to read your child's genetic report.

03

Managing IRD: Treatment Strategies and Building Your Care Team

Learn how to manage Infantile Refsum Disease (IRD). Discover treatment strategies, dietary needs like phytanic acid restriction, and how to build a care team.

Understanding the Zellweger Spectrum

Doctors now view Infantile Refsum Disease (IRD) as part of the Zellweger Spectrum Disorders (ZSD) [1]. In the past, doctors gave these conditions different names based on how severe the symptoms appeared at birth. Today, we understand they are all caused by the same underlying biological issue: mutations in PEX genes [3][4].

Within this spectrum, IRD is historically considered the milder end [5]. This means that while children with IRD face significant health challenges, they typically have more functional peroxisomes than children with the more severe “Zellweger Syndrome” seen at birth [1][6].

The Role of Peroxisomes

Think of peroxisomes as specialized organs within a cell that perform two vital jobs:

  1. Breaking down waste: They break down complex fats called Very Long Chain Fatty Acids (VLCFAs) and phytanic acid (a fat found in certain foods) [7][8].
  2. Building essentials: They help create important substances the body needs, like plasmalogens, which protect the brain and heart [9][10].

In children with IRD, the PEX genes (the instructions for building peroxisomes) have “typos.” This causes peroxisomes to be either missing or not working correctly, leading to a buildup of toxic fats and a shortage of essential ones [3][11].

IRD vs. Adult Refsum Disease: A Critical Distinction

Despite the similar names, Infantile Refsum Disease (IRD) and Adult Refsum Disease (ARD) are distinct conditions with different causes. Confusing the two online is common but problematic:

Feature Infantile Refsum Disease (IRD) Adult Refsum Disease (ARD)
Category A Zellweger Spectrum Disorder [1] A single-enzyme deficiency [7]
Genetic Cause Mutations in PEX genes (e.g., PEX1, PEX6) [3] Mutations in the PHYH or PEX7 genes [7]
Biochemical Hallmark High VLCFAs and phytanic acid [7][8] High phytanic acid only; VLCFAs are normal [7]
Organ Involvement Can affect liver, hearing, vision, and brain [12] Primarily affects vision, hearing, and nerves [13]

Prognosis and Life Expectancy

Because IRD falls on the milder end of the Zellweger Spectrum, the long-term prognosis is very different from classic Zellweger Syndrome. While infants with Zellweger Syndrome unfortunately often pass away within their first year, children with IRD typically live into late childhood, and many live well into adulthood [1][5]. Their clinical course is highly variable and depends on how well their remaining peroxisomes function.

How Rare is This and Finding Support

Zellweger Spectrum Disorders are very rare, occurring in approximately 1 in 90,000 births [14]. Because it is so rare, it is vital to find a community. Organizations like the Global Foundation for Peroxisomal Disorders (GFPD) offer incredible support, resources, and connections to other families navigating the exact same diagnosis [15].

Common questions in this guide

What is the difference between Infantile and Adult Refsum Disease?
Infantile Refsum Disease is a Zellweger Spectrum Disorder caused by mutations in PEX genes, resulting in high levels of VLCFAs and phytanic acid. Adult Refsum Disease is a completely different genetic condition caused by a single-enzyme deficiency where only phytanic acid levels are elevated.
What is the life expectancy for a child with Infantile Refsum Disease?
Because Infantile Refsum Disease is on the milder end of the Zellweger spectrum, children typically live into late childhood, and many live well into adulthood. The exact prognosis is highly variable and depends on how well their remaining cellular peroxisomes function.
What do peroxisomes do in the body?
Peroxisomes act as the recycling centers within your cells. They break down complex waste fats, such as Very Long Chain Fatty Acids (VLCFAs), and help build essential substances like plasmalogens that protect the brain and heart.
How common is Infantile Refsum Disease?
Zellweger Spectrum Disorders, which include Infantile Refsum Disease, are very rare and occur in approximately 1 in 90,000 births. Finding a dedicated community, such as the Global Foundation for Peroxisomal Disorders, can be highly beneficial for families.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which specific PEX gene variant was identified in my child’s genetic testing?
  2. 2.How does my child’s clinical presentation fit into the Zellweger Spectrum compared to other patients you have treated?
  3. 3.What were my child's Very Long Chain Fatty Acid (VLCFA) levels compared to their phytanic acid levels?
  4. 4.Can you explain why Infantile Refsum Disease is different from Adult Refsum Disease in terms of my child's future care?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (15)
  1. 1

    Severe Zellweger spectrum disorder due to a novel missense variant in the PEX13 gene: A case report and the literature review.

    Su L, Peng MZ, Chen XD, et al.

    Molecular genetics & genomic medicine 2024; (12(1)):e2315 doi:10.1002/mgg3.2315.

    PMID: 37962062
  2. 2

    Genome sequencing identifies a rare case of moderate Zellweger spectrum disorder caused by a PEX3 defect: Case report and literature review.

    Lee W, Costain G, Blaser S, et al.

    Molecular genetics and metabolism reports 2020; (25()):100664 doi:10.1016/j.ymgmr.2020.100664.

    PMID: 33101983
  3. 3

    Distinguishing PEX gene variant severity for mild, severe, and atypical peroxisome biogenesis disorders in Drosophila.

    Gomez VA, Kanca O, Jangam SV, et al.

    bioRxiv : the preprint server for biology 2024; doi:10.1101/2024.11.14.623590.

    PMID: 39605732
  4. 4

    Identification of a new frameshift homozygous variant of PEX3 gene in a preterm infant with profound global developmental delay and bilateral ptosis: a case report and updated literature review.

    Su J, Tao Y, Zhang L, Luo J

    BMC pediatrics 2026; (26(1)):81 doi:10.1186/s12887-025-06472-0.

    PMID: 41495707
  5. 5

    Development and validation of a severity scoring system for Zellweger spectrum disorders.

    Klouwer FCC, Meester-Delver A, Vaz FM, et al.

    Clinical genetics 2018; (93(3)):613-621 doi:10.1111/cge.13130.

    PMID: 28857144
  6. 6

    Serum very long-chain fatty acids (VLCFA) levels as predictive biomarkers of diseases severity and probability of survival in peroxisomal disorders.

    Stradomska TJ, Syczewska M, Jamroz E, et al.

    PloS one 2020; (15(9)):e0238796 doi:10.1371/journal.pone.0238796.

    PMID: 32946460
  7. 7

    Comparison of the Diagnostic Performance of C26:0-Lysophosphatidylcholine and Very Long-Chain Fatty Acids Analysis for Peroxisomal Disorders.

    Jaspers YRJ, Ferdinandusse S, Dijkstra IME, et al.

    Frontiers in cell and developmental biology 2020; (8()):690 doi:10.3389/fcell.2020.00690.

    PMID: 32903870
  8. 8

    Application of machine learning algorithms for the differential diagnosis of peroxisomal disorders.

    Subhashini P, Jaya Krishna S, Usha Rani G, et al.

    Journal of biochemistry 2019; (165(1)):67-73 doi:10.1093/jb/mvy085.

    PMID: 30295825
  9. 9

    A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers.

    Wangler MF, Hubert L, Donti TR, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2018; (20(10)):1274-1283 doi:10.1038/gim.2017.262.

    PMID: 29419819
  10. 10

    Development of a system adapted for the diagnosis and evaluation of peroxisomal disorders by measuring bile acid intermediates.

    Kawai H, Takashima S, Ohba A, et al.

    Brain & development 2023; (45(1)):58-69 doi:10.1016/j.braindev.2022.10.001.

    PMID: 36511274
  11. 11

    The many faces of peroxisomal disorders: Lessons from a large Arab cohort.

    Alshenaifi J, Ewida N, Anazi S, et al.

    Clinical genetics 2019; (95(2)):310-319 doi:10.1111/cge.13481.

    PMID: 30561787
  12. 12

    [Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review].

    Yang P, Zeng CZ, Tao XW, et al.

    Zhonghua er ke za zhi = Chinese journal of pediatrics 2024; (62(1)):43-48 doi:10.3760/cma.j.cn112140-20230914-00191.

    PMID: 38154976
  13. 13

    Identification of novel pathogenic variants in the PHYH gene and extending the phenotypic range in Refsum disease.

    Gregory-Evans CY, Lehman A, Mattman A, et al.

    Ophthalmic genetics 2026; (47(3)):283-286 doi:10.1080/13816810.2025.2591819.

    PMID: 41290216
  14. 14

    Carrier frequency estimation of Zellweger spectrum disorder using ExAC database and bioinformatics tools.

    Vasiljevic E, Ye Z, Pavelec DM, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2019; (21(9)):1969-1976 doi:10.1038/s41436-019-0468-3.

    PMID: 30846882
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    Emotional experience in parents of children with Zellweger spectrum disorders: A qualitative study.

    Bose M, Mahadevan M, Schules DR, et al.

    Molecular genetics and metabolism reports 2019; (19()):100459 doi:10.1016/j.ymgmr.2019.100459.

    PMID: 30815361

This page provides educational information about Infantile Refsum Disease and Zellweger Spectrum Disorders. It does not replace professional medical advice. Always consult your pediatric geneticist or neurologist regarding your child's specific care plan.

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