Research Report Summary

Adult Refsum disease is a rare metabolic disorder caused by the accumulation of phytanic acid in tissues like the retina and nervous system. This buildup occurs due to deficiencies in peroxisomal enzymes, particularly linked to pathogenic variants in the PHYH or PEX7 genes, which were identified through genetic research on Refsum disease. 1 2 The condition’s prevalence is estimated to be around 1 in one million in the UK, though it is not well-studied in Australia. 3

Key Features

The disease typically presents with symptoms like retinitis pigmentosa (RP) in late childhood or adolescence, and variable combinations of anosmia (loss of smell), polyneuropathy (sensory and motor), deafness, ataxia, and bony changes (particularly short metacarpals and metatarsals present from birth). 4 5

In adulthood, RP is often the first noticeable symptom, but other syndromic features may not develop until later. As in the case described, a 40-year delay in diagnosis may result, especially if the disease’s syndromic features are subtle or absent. 6 7

Refsum disease diagnosis

A correct Refsum disease diagnosis is crucial as it allows for effective management, primarily involving dietary changes to limit phytanic acid intake. Patients must avoid high-phytanic acid foods like dairy, beef, lamb, and certain seafood. 8 9 Treatment may also include plasma exchange or lipid apheresis in acute settings, though dietary management remains the primary treatment. 10 If untreated, Refsum disease can lead to severe complications, including sudden death due to cardiac issues. 11 12

Case Report

The study’s case report highlights the story of a 53-year-old woman who, after being diagnosed with RP at 11 years, was not diagnosed with Refsum disease until 40 years later. Genetic testing confirmed biallelic pathogenic variants in the PHYH gene. 13 14 Prior to diagnosis, she received treatment for RP without awareness of the metabolic disorder, leading to missed opportunities for earlier intervention. 

Importance of Correct Diagnosis
  1. Early Treatment to Prevent Progression 
    Early diagnosis enables dietary restrictions that can significantly slow disease progression and reduce the risk of severe outcomes, including heart arrhythmias and sudden death. For example, the patient’s adherence to a low-phytanic acid diet since diagnosis has been essential in managing her condition. 15
  2. Avoiding Harmful Dietary Advice
    Misunderstanding the condition can lead to incorrect dietary recommendations. For instance, RP patients are often advised to consume fish and leafy vegetables for “retinal health,” but these foods are high in phytanic acid, which can exacerbate Refsum disease. 16
  3. Genetic Testing and Multidisciplinary Care 
    Genetic testing is a powerful tool in confirming rare inherited conditions like Refsum disease. As genetic knowledge expands, more patients can be accurately diagnosed, which improves management strategies. The case illustrates the importance of multidisciplinary care involving specialists in metabolic diseases, genetics, and ophthalmology. 17 18
  4. Role of Eye Care Providers 
    Eye care providers should be aware of the potential for syndromic causes of RP, especially rare diseases like Refsum. Investigating other symptoms, such as hearing loss or anosmia, can be critical for diagnosing complex conditions. Genetic testing can be especially beneficial, and eye care providers play a key role in referring patients for genetic evaluation when syndromic RP is suspected. 19
  5. Barriers to Diagnosis and Management 
    The case emphasises several barriers, including disjointed healthcare systems and limited access to genetic testing. 20 Awareness of these challenges is vital for improving diagnosis and care for patients with rare syndromic conditions. 21 
Conclusion

Refsum disease diagnosis is essential for initiating appropriate management and preventing severe outcomes like vision and hearing loss, as well as life-threatening cardiac complications. Early recognition of its syndromic features, including RP, is critical, and genetic testing is a key tool in confirming the diagnosis. Improved awareness among healthcare providers, especially ophthalmologists and general practitioners, can reduce diagnostic delays and significantly improve patient quality of life through tailored interventions. 22 23 24

 

Access the published research report here