Refsum disease is a rare autosomalrecessive neurometabolic peroxisomal disorder, due to the accumulation of phytanic acid in blood and tissues, including brain tissue, first indentified by sigvald refsum 1. This chapter presents the answers to the questions raised on refsums disease, explained with reference to the case of alan, who was diagnosed with retinitis pigmentosa. 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. Refsum disease information page national institute of. The finding that both diseases are paralleled by tissue lipidstorage of phytanic acid or that of vlcfas, respectively, led to the hypothesis that an impaired cerebral metabolism of phytanic acid and that of.
Refsum disease is an autosomal recessive lipidstorage disorder mim266500 characterized by the accumulation of the branchedchain fatty acid phytanic acid 3,7,11,15tetramethylhexadecanoic acid in tissues and body fluids of patients. Vaishali choksi, ellen hoeffner, ercan karaarslan, cengiz yalcinkaya, and sinan cakirer. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. Due to a genetic abnormality, people with ard disease lack the enzyme in peroxisomes that break down phytanic acid, a type of fat found in certain foods. Although reduced smell function has been described in ard, its value in the diagnosis of the condition has not been fully evaluated. Refsums disease rd, also called heredopathia atactica polyneuritiformis, is a rare disorder with an autosomal recessive mode of inheritance, characterized by accumulation of phytanic acid. The vision loss associated with refsum disease is caused by an eye disorder called retinitis pigmentosa. The physiological role of phytanic acid is unknown. Refsums disease is an inherited metabolic disorder in which a metabolite of branched chain fatty acids accumulates due to lack of appropriate oxidative enzymes.
It is one of several disorders named after norwegian neurologist sigvald bernhard refsum 19071991. Refsum disease, peroxisomes and phytanic acid oxidation. Infantile refsums disease, neonatal ald and zellweger syndrome are considered to be a disease continuum. Cochlear implantation in refsum disease with facial nerve.
Clinically, these patients have mental retardation, pigmentary retinopathy, sensorineural deafness, dysmorphic features, hepatomegaly and may have a peripheral neuropathy. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Midlife diagnosis of refsum disease in siblings with. Phytanic acid storage disease also known as refsum disease is an autosomal recessive disease resulting from the inability to metabolize phytanic acid due to a defect in the phytanoylcoa hydrolase. The dietetic intervention plan includes achieving weight maintenance. Clinicians will also find much of interest here, especially the section on diet for treatment of adult refsum s disease. Phytanic acid in patients with refsums syndrome and.
Refsum disease is one of a family of genetic disorders known as the leukodystrophies in. The genes responsible for the failure in the metabolism of phytanic acid have been traced to the short arm of chromosome 10 10pterp11. On a highly restricted diet the phytanic acid levels in blood and in adipose tissue fell dramatically over a. Infantile refsum disease is the mildest of a group of disorders known as. Livingdonor liver transplantation from a heterozygous.
Refsums disease is an inherited disorder of fatty acid oxidation. Refsum disease is a rare autosomal recessive disease associated with mutations of phytanoylcoa hydroxylase 90% and peroxisomal biogenesis factor 7 10% genes that are normally involved in phytanic acid degradation. All structured data from the file and property namespaces is available under the creative commons cc0 license. Refsum disease is characterized by anosmia and earlyonset retinitis pigmentosa, which are both universal findings with variable combinations. Refsum disease rd is a neurocutaneous syndrome that is characterized biochemically by the accumulation of phytanic acid in plasma and tissues. The discovery of markedly elevated levels of the branchedchain fatty acid phytanic acid in certain patients marked refsum disease as a disorder of lipid metabolism. The objective was to describe a case of bilateral cochlear implantation in a 59yearold man with hearing and visual impairment due to refsums disease. Adult refsums disease information for patients the. Refsum disease heredopathia atactica polyneuritiformis was first described in 1946 and is a rare recessively inherited metabolic disease affecting phytanic acid metabolism. Metabolic studies in two patients with refsums syndrome provide further evidence that the phytanic acid stored has a strictly exogenous origin. Infantile refsum disease ird, is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the zellweger spectrum. The diagnosis is confirmed by the presence of phytanic acidaemia. The fraction of the absorbed dose converted to 14 co 2 in 12 hours was 3.
Refsum disease was first recognized as a distinct disease entity by sigvald refsum in the 1940s. Pdf refsum disease was first recognized as a distinct disease entity by sigvald. Refsum disease is a rare autosomal recessive disorder characterized biochemically by accumulation of phytanic acid in blood and tissues, including fat and neurons. A variant that occurs in children is called infantile refsum disease ird. Welcome to the adult refsum s disease website it contains. Information for patients, their families, and helpers what adult refsum s disease is, and what to do if you are affected by it. Midlife diagnosis of refsum disease in siblings with retinitis. Adult refsum disease ard is a rare genetic disease that causes weakness or numbness of the hands and feet peripheral neuropathy. Phytanic acid levels are elevated because of a deficiency of the enzyme phytanoylcoa hydroxylase phyh. Driving refsum research is at the center of what we do. Following genetic testing, he has been diagnosed with adult refsums disease. Refsum disease is inherited as an autosomal recessive trait, the gene encoding phytanoylcoa hydroxylase, phyh, mapping to 10p. Magnetic resonace imaging findings in a case of infantile. Files are available under licenses specified on their description page.
Refsum disease is a rare metabolic disorder, which is characterized by the accumulation of phytanic acid in the blood and tissues, including the brain. Besides retinal degeneration or retinal dystrophy associated with adult onset. Pdf refsum disease, peroxisomes and phytanic acid oxidation. Pbdzss is a group of inherited genetic disorders that damage the white matter of the brain and affect motor movements. These are disorders of the peroxisomes that are clinically similar to zellweger syndrome and associated with mutations in the pex family of genes. Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations. Information for clinicians more detailed and specialist material. Refsum disease, infantile form genetic and rare diseases. Refsum disease nord national organization for rare. Identification of pahx, a refsum disease gene nature. Phytanic acid storage disease refsums disease, in vinken pj, bruyn gw eds. Refsum disease is an autosomal recessive disorder characterized by retinitis pigmentosa, peripheral poly neuropathy, cerebellar ataxia and increased cerebrospinal fluid protein1.
Refsums diseaseuse of the intestinal lipase inhibitor. Infantile refsum disease ird is a medical condition within the zellweger spectrum of perixisome biogenesis disorders pbds, inherited genetic disorders that damage the white matter of the brain and affect motor movements. Refsums disease is a rare, autosomal recessive neurometabolic disease, characterised biochemically by accumulation of phytanic acid in blood and tissues. A variant of this condition that occurs in young children is called infantile refsum disease. The main treatment for adult refsums disease is dietary and requires the expertise of a dietitian. Patients with refsum disease are unable to degrade phytanic acid because of a deficient activity of phytanoylcoa hydroxylase phyh, a peroxisomal enzyme catalyzing the first step of phytanic acid a. Information for patients, their families, and helpers what adult refsums disease is, and what to do if you are affected by it. Welcome to the adult refsums disease website it contains. Pbds are part of a larger group of disorders called the leukodystrophies. Refsum disease is an inherited condition that causes vision loss, absence of the sense of smell anosmia, and a variety of other signs and symptoms. Refsums disease is characterised by phytanic acid accumulation in the blood.
Refsum disease is a peroxisomal disorder caused by the impaired. When the weight falls the fat stores are used up for energy, but the phytanic acid released from these stores is not removed, so it accumulates. Infantile refsum disease is the mildest of a group of disorders known as peroxisome biogenesis disorders, zellweger syndrome spectrum pbdzss. Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. From the regional neurological unit, brook general hospital. In one of those satisfying quirks of timing, it was precisely 25 years ago that another article appeared in neurology by refsum and colleagues describing the successful dietary treatment of a patient with refsum disease. Adult refsums disease ard is characterised by the presence of retinitis pigmentosa, ataxia, deafness, sensory neuropathy, and bony changes. Symptoms of refsum disease may include vision impairment, degenerative nerve disease, failure of.
This disorder affects the retina, the lightsensitive layer at the back of the eye. Orally administered tracer doses of phytolu14 c were well absorbed both by seven normal control subjects 61 to 94% and by two patients with refsums disease 74 and 80%. Refsum disease is an autosomal recessive neurological disease that results in the overaccumulation of phytanic acid in cells and tissues. Symptoms may include a degenerative nerve disease peripheral neuropathy, failure of muscle coordination ataxia, retinitis pigmentosa a progressive vision disorder, and bone and skin changes. This page was last edited on 9 february 2019, at 15. Also termed heredopathia atactica polyneuritiformis, it was first identified as a clinical entity by refsum in the 1940s.
Refsum disease is an inherited condition that causes vision loss, loss of. Wanders, ronald ja, hans r waterham, and bart leroy. Infantile refsums disease refsoomz is an inherited metabolic disorder that is characterized by the abnormal accumulation of phytanic acid in blood plasma and tissues. Livingdonor liver transplantation from a heterozygous parent for infantile refsum disease masatoshi matsunami, md, a nobuyuki shimozawa, md, phd, b akinari fukuda, md, phd, a tadayuki kumagai, md, c masaya kubota, md, phd, c pin fee chong, md, d mureo kasahara, md, phda a organ transplantation center, and cdivision of neurology, national center for child health and development, tokyo. Infantile refsum disease information page national. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems that develop later in life. First, the patient should eat sufficiently well to prevent loss of weight. Global dare foundations mission is to promote worldwide awareness and better quality of life for all who are diagnosed with adult refsum disease. Refsums disease dietetic and nutrition case studies. Infantile refsums disease is one of the pbd disorders. Refsum disease genetic and rare diseases information. Ataxia with loss of purkinje cells in a mouse model for.
Refsum disease nord national organization for rare disorders. Our goal is to support refsum disease research, education initiatives, awareness, and advocacy. Refsums disease heredopathia atactica polyneuritiformis, hap is an inherited neurological disorder associated with storage of the branchedchain fatty acid, phytanic acid 3,7,11,15tetramethylhexadecanoic acid. Clinicians will also find much of interest here, especially the section on diet for treatment of adult refsums disease. A variant of this disease that occurs in children is called infantile refsum disease. Peroxisome biogenesis disorders, in turn, are part of a larger group of disorders called leukodystrophies. Infantile refsum disease ird is a rare autosomal recessive disorder of peroxisome biogenesis characterized by generalized peroxisomal metabolic dysfunction, including accumulation of very longchain fatty acids vlcfas and phytanic acid pa, as well as decreased plasmalogen contents pl. Refsum disease is a rare disorder of lipid metabolism that is inherited as a recessive trait. An effective therapy for this intractable disease has not been established, and only supportive. Amsterdam, northholland publishing co, 1975, vol 21, part 1, pp 181229. He has recently been complaining of numb feet, scaly, itchy skin and deteriorating vision. The pathophysiology of refsum disease is characterized by accumulation of phytanic acid in plasma and tissues 200.
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