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1.  Refsum's disease: characterization of the enzyme defect in cell culture 
Journal of Clinical Investigation  1969;48(6):1017-1032.
Refsum's disease (heredopathia atactica polyneuritiformis, HAP) is an inherited neurological disorder associated with storage of the branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid). Cultured fibroblasts derived from skin biopsies of HAP patients did not contain elevated levels of phytanate, yet showed rates of phytanate-C-14C oxidation less than 3% of those seen in cells from control subjects. Cells of control subjects converted phytanate to α-hydroxyphytanate, to pristanate (the [n-1] homologue of phytanate) and to 4,8,12-trimethyltridecanoate, compounds previously identified as intermediates on the major pathway for phytanate metabolism in animals, providing the first direct evidence that this same oxidative pathway is operative in human cells. None of these breakdown products could be found after incubation of phytanate with HAP cells. Labeled α-hydroxyphytanate and labeled pristanate were oxidized at normal rates by HAP cells. Oxidation of the latter proceeded at normal rates both when added to the medium at very low tracer levels and at levels 100 times greater. Phytanate was incorporated into and released from lipid esters at normal rates by HAP cells. Elevated levels of free phytanate in the medium were no more toxic to HAP cells than to control cells over the 48- to 72-hr exposures involved in these studies, as evidenced by morphologic criteria and by ability to oxidize labeled palmitate. These findings are consistent with the hypothesis that the cells from HAP patients are deficient in a single enzyme involved in the α-hydroxylation of phytanate, while the enzymes involved in later steps are present at normal or near-normal levels.
PMCID: PMC322316  PMID: 4181593
2.  Patterns of Refsum's disease. Phytanic acid oxidase deficiency. 
Archives of Disease in Childhood  1984;59(3):222-229.
Four children each exhibiting a profound deficiency of phytanic acid oxidase activity in cultured skin fibroblasts but with very different phenotypes, are described. A consistently raised plasma phytanic acid value, generally considered to be pathognomonic for Refsum's disease (phytanic acid oxidase deficiency), was observed in three of these children but not in the fourth, who also showed no evidence of accumulation of phytanic acid in liver or fat biopsies. Our data suggest that the clinical diagnosis of Refsum's disease in children is more difficult because the full spectrum of clinical features usually observed in adults with the disorder is not always present. Moreover, a failure to detect a raised plasma phytanic acid value may not necessarily indicate normal fibroblast phytanic acid oxidase activity.
Images
PMCID: PMC1628542  PMID: 6201142
3.  Refsum Disease Presenting with a Late-Onset Leukodystrophy 
JIMD Reports  2015;19:7-10.
Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized by phytanic acid storage. Clinical symptoms usually begin in late childhood before the age of 20. Typical clinical presentation includes nyctalopia caused by retinitis pigmentosa, and anosmia. After 10–15 years, deafness, cerebellar ataxia, polyneuropathy, ichthyosis, and cardiac arrhythmia can occur.
We report the case of a very late-onset adult Refsum disease presenting with marked cognitive decline and severe leukoencephalopathy, without peripheral nervous system involvement. Brain MRI showed a leukoencephalopathy involving the periventricular white matter, subcortical area, and the brainstem with relative sparing of juxtacortical U fibers. This was associated with severe cortical and subcortical atrophy with ventricle dilatation. MR spectroscopy showed a marked increase in the choline/NAA ratio. Elevated plasma phytanic acid level was found, whereas plasma levels of pristanic and very long chain fatty acids were normal. The patient is homozygous for a previously undescribed PHYH frameshift mutation. Whether the very unusual phenotype is related to this peculiar mutation remains unclear.
doi:10.1007/8904_2014_355
PMCID: PMC4501234  PMID: 25604618
Adult Refsum disease; Dementia; Gait apraxia; Leukodystrophy
4.  Studies on the Metabolic Error in Refsum's Disease* 
Journal of Clinical Investigation  1967;46(3):313-322.
Studies utilizing mevalonic acid-2-14C and D2O as precursors failed to provide evidence for an appreciable rate of endogenous biosynthesis of phytanic acid in a patient with Refsum's disease.
Orally administered tracer doses of phytol-U-14C were well absorbed both by seven normal control subjects (61 to 94%) and by two patients with Refsum's disease (74 and 80%).
The fraction of the absorbed dose converted to 14CO2 in 12 hours was 3.5 and 5.8% in Refsum's disease patients and averaged 20.9% in seven control subjects.
Labeled phytanic acid was demonstrated in the plasma of both control subjects and patients given phytol-U-14C, establishing phytol in the diet as a potential precursor of phytanic acid. This labeled phytanic acid had disappeared almost completely from the plasma of the seven control subjects by 24 to 48 hours, whereas it persisted at high concentrations in the plasma of the two patients for many days.
We conclude that the phytanic acid accumulating in Refsum's disease is primarily of exogenous origin and that patients with Refsum's disease have a relative block in the degradation of phytanic acid and possibly other similar branched-chain compounds. This may relate to a deficiency in mechanisms for release of phytanic acid from stored ester forms or, more probably, to reactions essential to oxidative degradation of the carbon skeleton.
PMCID: PMC297052  PMID: 4164676
5.  Localization of the oxidative defect in phytanic acid degradation in patients with refsum's disease 
Journal of Clinical Investigation  1969;48(6):1033-1040.
The rate of oxidation of phytanic acid-U-14C to 14CO2 in three patients with Refsum's disease was less than 5% of that found in normal volunteers. In contrast, the rate of oxidation of α-hydroxyphytanic acid-U-14C and of pristanic acid-U-14C to 14CO2, studied in two patients, while somewhat less than that in normal controls, was not grossly impaired. These studies support the conclusion that the defect in phytanic acid oxidation in Refsum's disease is located in the first step of phytanic acid degradation, that is, in the alpha oxidation step leading to formation of α-hydroxyphytanic acid.
The initial rate of disappearance of plasma free fatty acid radioactivity after intravenous injection of phytanic acid-U-14C (t½ = 5.9 min) was slower than that seen with pristanic acid-U-14C (t½ = 2.7 min) or palmitic acid-1-14C (t½ = 2.5 min). There were no differences between patients and normal controls in these initial rates of free fatty acid disappearance for any of the three substrates tested.
There was no detectable lipid radioactivity found in the plasma 7 days after the injection of palmitic acid-1-14C or pristanic acid-U-14C in either patients or controls. After injection of phytanic acid-U-14C, however, the two patients showed only a very slow decline in plasma lipid radioactivity (estimated t½ = 35 days), in contrast to the normals who had no detectable radioactivity after 2 days. Incorporation of radioactivity from phytanic acid-U-14C into the major lipid ester classes of plasma was studied in one of the patients; triglycerides accounted for by far the largest fraction of the total present between 1 and 4 hr.
PMCID: PMC322317  PMID: 4181594
6.  Refsum's Disease—Use of the Intestinal Lipase Inhibitor, Orlistat, as a Novel Therapeutic Approach to a Complex Disorder 
Journal of Obesity  2010;2011:482021.
Refsum's Disease is an inherited metabolic disorder in which a metabolite of branched chain fatty acids accumulates due to lack of appropriate oxidative enzymes. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. Besides retinal degeneration or retinal dystrophy associated with adult onset retinitis pigmentosa, additional symptoms include chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, as well as skeletal, cardiac, hepatic, and renal abnormalities. Current management includes avoidance of dietary sources of branched chain fatty acids and regular plasmapheresis to prevent accumulation of these compounds to ameliorate progressive neurological deficits. Two brothers with Refsum's disease who experienced progressive symptoms despite optimal diet and plasmapheresis were commenced on a novel therapy. We report the effect of the intestinal lipase inhibitor, Orlistat, which led to significant reduction (P-value <0.001 on 2-sample unpaired t-test) of mean preplasmapheresis phytanic acid levels with retardation of the progression of most of their dermatological and neurological symptoms.
doi:10.1155/2011/482021
PMCID: PMC2943115  PMID: 20871815
7.  Refsum's syndrome: report of three cases 
The case-reports of three cases of Refsum's syndrome are presented, and the underlying metabolic abnormality discussed. The effect of treatment with a low-phytanic acid diet in one case is described.
Images
PMCID: PMC493598  PMID: 5531900
8.  Plasma exchange in the treatment of Refsum's disease (heredopathia atactica polyneuritiformis). 
Five cases of heredopathia atactica polyneuritiformis (HAP--Refsum's disease) were treated by serial plasma exchanges. In all patients a reduction in calorie intake and body weight had been associated with a rise in plasma phytanic acid, followed by an exacerbation of the ataxia and neuropathy. Lowering the plasma phytanic acid by plasma exchange produced a rapid clinical improvement. The main indication for plasma exchange in HAP is a severe or rapidly worsening clinical condition. A lesser indication is failure of dietary management to reduce a high plasma phytanic acid level.
PMCID: PMC1014432  PMID: 1716665
9.  Smell testing: an additional tool for identification of adult Refsum's disease 
Objective: To investigate the prevalence and degree of olfactory dysfunction in patients with ARD.
Method: The olfactory function of 16 patients with ARD was assessed using the quantitative University of Pennsylvania Smell Identification Test (UPSIT).
Results: All patients had complete anosmia or grossly impaired smell function with a mean UPSIT score of 14.7 (SD 4.7) (normal>34) despite having been treated with an appropriate diet for a median of 15 years (range 1–25).
Conclusions: Identification of ARD patients can be facilitated by using the UPSIT in combination with the presence of retinitis pigmentosa, even if they have no neurological or bony features. Phytanic acid screening should be performed in any patient manifesting these two signs.
doi:10.1136/jnnp.2003.026690
PMCID: PMC1739246  PMID: 15314127
10.  Clinicopathological study of Refsum's disease with particular reference to fatal complications. 
The clinical and pathological findings in two brothers with biochemically diagnosed Refsum's disease are given. The pathology, in general, was that already described in this condition. An unusual complication in one case was the development of renal failure. Death was caused in the other by heart failure.
Images
PMCID: PMC493025  PMID: 77310
11.  Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions 
BMC Physiology  2010;10:19.
Background
It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism.
Results
Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes.
Conclusion
We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.
doi:10.1186/1472-6793-10-19
PMCID: PMC2964658  PMID: 20932325
12.  Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study 
PLoS Medicine  2010;7(12):e1000384.
David Boulware and colleagues investigate clinical features in a prospective cohort with AIDS and recent cryptococcal meningitis after initiation of antiretroviral therapy to identify biomarkers for prediction and diagnosis of CM-IRIS (cryptococcal meninigitis-related immune reconstitution inflammatory syndrome).
Background
Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.
Methods and Findings
We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1–5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p≤0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile). Pre-ART CRP level >32 mg/l alone was associated with future death (OR = 8.3, 95% CI 2.7–25.6, p<0.001).
Conclusions
Pre-ART increases in Th17 and Th2 responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-α, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since 1981, AIDS has killed more than 25 million people and about 33 million people are now infected with HIV, which causes AIDS. HIV, which is most often transmitted through unprotected sex with an HIV-infected partner, infects and kills immune system cells. Eventually, the immune system becomes so weak that unusual infections begin to occur. These “opportunistic” infections are infections that take advantage of the opportunity offered by a weakened immune system. One common and deadly opportunistic infection in people affected by AIDS is cryptococcal meningitis (CM), an infection around the brain that is caused by the fungus Cryptococcus neoformans. About one million cases of CM occur every year. CM can be treated with a drug called amphotericin but usually recurs unless another drug called fluconazole is taken daily thereafter. HIV therapy is lifesaving by suppressing the HIV virus and allowing immune system recovery. This immune recovery also helps to prevent the recurrence of CM.
Why Was This Study Done?
Unfortunately, HIV therapy can also elicit a serious condition called immune reconstitution inflammatory syndrome (IRIS) in people with CM and AIDS. IRIS is an exaggerated inflammatory immune response that kills up to one-third of affected people. Inflammation, which is characterized by swelling and redness, is the body's first defense against infection, but uncontrolled inflammation causes widespread tissue damage. Experts think that CM-IRIS may be the result of an unbalanced recovery of the immune system leading to an inappropriate immune response to persisting C. neoformans fragments and proteins that are slowly cleared from the body over months. Unfortunately, it is impossible to predict which individuals with CM and AIDS will develop IRIS when they are given HIV therapy. In this prospective study, the researchers investigated clinical features and cytokine profiles in a group of Ugandans with AIDS and recent CM for one year after starting HIV therapy to identify biomarkers that could be used to predict and diagnose CM-IRIS. Cytokines are proteins secreted by immune system cells that regulate the immune response; biomarkers are proteins found in the blood that indicate specific diseases.
What Did the Researchers Do and Find?
The researchers enrolled 101 Ugandans with AIDS and recent CM who had not previously received HIV therapy. They compared cytokine patterns in individuals who did and did not subsequently develop IRIS after starting HIV therapy. Overall, 45% of the patients developed IRIS. Deaths occurred in 36% of the patients who developed IRIS and in 21% of those who did not develop IRIS. Patients who developed CM-IRIS after starting HIV therapy had 4-fold higher baseline concentrations of cryptococcal antigen in their blood than patients who did not develop CM-IRIS. Prior to starting HIV therapy, higher levels of the cytokines IL-4 and IL-17 and lower levels of four cytokines—TNF-α, G-CSF, GM-CSF, and VEGF—predicted IRIS development, and an algorithm (formula) based on the baseline levels of seven serum biomarkers was able to group the patients into high, moderate, and low risk of IRIS. After starting HIV therapy, increasing levels of the inflammatory proteins C-reactive protein and D-dimer, and of several cytokines, were associated with an increased risk of IRIS. At the time of IRIS onset, the levels of many proinflammatory cytokine increased. Biomarkers also predicted death after starting HIV therapy with increasing levels of IL-17, decreasing levels of GM-CSF, and a C-reactive protein level of more than 32 mg/l (four times higher than normal) predicted death within one year.
What Do These Findings Mean?
These findings support the hypothesis that some AIDS patients who have a very damaged immune system have a very poor initial immune response and poor clearance of cryptococcus, which predisposes them to IRIS. The findings also identify three distinct phases of IRIS development. Before HIV therapy, a very damaged immune system with a lack of inflammatory responses to infection or inappropriate responses leads to ineffective clearance of the organism and its antigens. After HIV therapy is started, the presence of copious antigens promotes proinflammatory signaling to the immune system. As the immune system recovers proinflammatory immune cells are promoted. Finally, at the time of IRIS, a generalized “cytokine storm” occurs, which is potentially fatal when this inflammation occurs in the brain. The biomarkers identified here as indicators of a predisposition to IRIS need to be validated in more patients in more countries before they can be used as a clinical tool for predicting the risk of IRIS. If they are validated, they could help clinicians decide when to start HIV therapy in patients with AIDS and recent CM, and could guide the use of therapies that could help prevent the abnormal inflammatory responses.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000384.
The US National Institute of Allergy and Infectious Diseases provides information on HIV infection and AIDS
HIV InSite has information on all aspects of HIV/AIDS, including Knowledge Base Chapters on cryptococcosis and HIV and on the clinical implications of IRIS
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including HIV-related opportunistic infections (in English and Spanish)
The MedlinePlus encyclopedia has a page on cryptococcal meningitis (in English and Spanish)
AIDS InfoNet provides fact sheets on many HIV/AIDS topics, including a fact sheet on cryptococcal meningitis (in several languages) and treatment guidelines for opportunistic infections
doi:10.1371/journal.pmed.1000384
PMCID: PMC3014618  PMID: 21253011
13.  Effect of dairy fat on plasma phytanic acid in healthy volunteers - a randomized controlled study 
Background
Phytanic acid produced in ruminants from chlorophyll may have preventive effects on the metabolic syndrome, partly due to its reported RXR and PPAR- α agonist activity. Milk from cows fed increased levels of green plant material, contains increased phytanic acid concentrations, but it is unknown to what extent minor increases in phytanic acid content in dairy fat leads to higher circulating levels of phytanic acid in plasma of the consumers.
Objective
To investigate if cow feeding regimes affects concentration of plasma phytanic acid and risk markers of the metabolic syndrome in human.
Design
In a double-blind, randomized, 4 wk, parallel intervention study 14 healthy young subjects were given 45 g milk fat/d from test butter and cheese with 0.24 wt% phytanic acid or a control diet with 0.13 wt% phytanic acid. Difference in phytanic acid was obtained by feeding roughage with low or high content of chlorophyll.
Results
There tended to be a difference in plasma phytanic acid (P = 0.0730) concentration after the dietary intervention. Plasma phytanic acid increased significantly within both groups with the highest increase in control group (24%) compared to phytanic acid group (15%). There were no significant effects of phytanic acid on risk markers for the metabolic syndrome.
Conclusions
The results indicate that increased intake of dairy fat modify the plasma phytanic acid concentration, regardless of cows feeding regime and the minor difference in dietary phytanic acid. Whether the phytanic acid has potential to affects the risk markers of the metabolic syndrome in human still remain to be elucidated.
Trial Registration
ClinicalTrials.gov: NCT01343576
doi:10.1186/1476-511X-10-95
PMCID: PMC3127790  PMID: 21663648
Phytanic acid; cow-feeding regime; absorption; fatty acid; total cholesterol; LDL cholesterol; HDL cholesterol; C-reactive protein; insulin; glucose
14.  Ataxia and other data reviewed in Charcot-Marie-Tooth and Refsum's disease. 
The author reports his experience on Refsum's disease and that gained after personally examining in detail 64 patients with Charcot-Marie-Tooth disease over the past ten years. The "cerebellar" inco-ordination in Charcot-Marie-Tooth disease (with or without distal wasting) and in Refsum's disease is analysed. Some variations in the motor and sensory neuropathy of Charcot-Marie-Tooth disease and Refsum's disease are discussed. The adequacy of motor conduction velocity in genetically distinguishing types of the above mentioned familial peripheral neuropathies is reviewed. Data on the neuropathy assessed by modern techniques of three original patients of Roussy and Levy (1926) are given. The possibility of extensor plantar responses in patients with Charcot-Marie-Tooth and Refsum's disease without structural lesion of the pyramidal tract is pointed out. The existence of the association between Friedreich's ataxia and Charcot-Marie-Tooth disease is criticised. It is emphasised that spinocerebellar degeneration (other than Friedreich's ataxia) presenting with distal limb weakness and wasting and sensory impairment may mimic Charcot-Marie-Tooth disease.
PMCID: PMC491688  PMID: 6186770
15.  Morphological Alterations Within the Peripheral Fixation of the Iris Dilator Muscle in Eyes With Pigmentary Glaucoma 
Purpose.
To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG).
Methods.
Using 63 control eyes (age 18 months–99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed eyes from three donors aged 38, 62, and 74 years.
Results.
In normal eyes, the peripheral end of the iris dilator muscle is arranged in a sphincter-like manner. Arcade-shaped tendinous connections associated with myofibroblasts (iridial strands) anchor the iris dilator within the elastic–fibromuscular ciliary meshwork that also serves as fixation area for the elastic tendons of the inner ciliary muscle portions. The iridial strands are innervated and can adapt their length during accommodation. The PG eyes show incomplete circular bundles and iridial strands that are mainly anchored to the iris stroma and the flexible uveal parts of the trabecular meshwork.
Conclusions.
The normal anchorage of the peripheral iris dilator and its presumably neuronally regulated length adaptation stabilize the peripheral iris during accommodation. Insufficient fixation in PG could promote posterior bowing of the iris with rubbing against the zonular fibers and pigment liberation from the iris pigmented epithelium.
The peripheral iris dilator muscle ends as a sphincter-like bundle and is connected to the ciliary body via contractile tendinous strands that are anchored within the musculoelastic network of the inner ciliary meshwork. This fixation appears to be altered in eyes with pigmentary glaucoma.
doi:10.1167/iovs.13-13765
PMCID: PMC4453212  PMID: 24938519
iris dilator muscle; anchorage; pigmentary glaucoma; morphology; immunohistochemistry
16.  Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report 
Introduction
Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.
Case presentation
We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.
Conclusion
It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.
doi:10.1186/1752-1947-2-80
PMCID: PMC2275283  PMID: 18336720

Results 1-25 (1714967)