Refsum s disease is a rare, autosomal recessive disorder due to mutations in the gene encoding phytanoyl. The gene locus is on chromosome 7q21q22 and transmission of the disorder. It is almost exclusively of exogenous origin and is delivered mainly from dietary plant chlorophyll and, to a lesser extent, from. Infantile refsum disease is the mildest of a group of disorders known as. Symptoms include retinitis pigmentosa, loss of hearing, loss of smell, and more. Human genome landmarks oak ridge national laboratory. Mar 20, 2006 refsum disease is characterized by anosmia and earlyonset retinitis pigmentosa, which are both universal findings with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. About 60 cases of refsum disease rd have been reported worldwide.
Refsum disease rd, also called heredopathia atactica polyneuritiformis, is a rare disorder with an autosomal recessive mode of inheritance, characterized by accumulation of phytanic acid. A common branched chain fatty acid, phytanic acid, is shown below. Refsums diseaseuse of the intestinal lipase inhibitor, orlistat, as. Infantile refsum disease is a rare inborn error of phytanic acid metabolism. Iatrogenic phospholipidosis mimicking fabry disease. Cochlear implantation in refsum disease with facial nerve en. Infantile refsums disease phytanic acid storage disease. Refsum disease is a rare disorder of lipid metabolism that is inherited as a recessive trait. Adult refsums disease information for patients the facts. Ichthyosis may be classified in syndromic or nonsyndromic forms based on. Refsums dis ease hereditary motor and sensory neuropathy type iv is a rare autosomal recessive condition first characterized by sigvald refsum in 1945. Two brothers with refsums disease who experienced progressive symptoms despite optimal diet and plasmapheresis were. Infantile refsum disease information page national.
Previously, surgical intervention was limited to one technique, nissen fundoplication. Refsum disease, infantile mucopolysaccharidosis osteoporosis, postmenopausal, susceptibility citrullinemia, adultonset type ii ulcerative colitis, susceptibility to adenoma, downregulated in chloride diarrhea, congenital, finnish type cardiomyopathy, familial hypertrophic renal cell carcinoma, papillary, familial and sporadic. Mar 27, 2019 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. Refsum disease is a peroxisomal disorder caused by the impaired.
Find, read and cite all the research you need on researchgate. This chapter presents the answers to the questions raised on refsum s disease, explained with reference to the case of alan, who was diagnosed with retinitis pigmentosa. Pbdzss is a group of inherited genetic disorders that damage the white matter of the brain and affect motor movements. Refsum disease, infantile form genetic and rare diseases. Nov 09, 2011 refsum disease is an inherited condition that causes vision loss, loss of smell anosmia, and a variety of other signs and symptoms. Information for patients, their families, and helpers what adult refsum s disease is, and what to do if you are affected by it. Refsum disease nord national organization for rare. Refsum disease genetic and rare diseases information. Localization of refsum disease with increased pipecolic. About 30 mutations in this gene have been identified. Classic refsum disease the medical biochemistry page. A variant that occurs in children is called infantile refsum disease ird. 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.
It differs from classic refsum disease in that infantile refsum disease is a generalized peroxisomal disorder resulting from failure of the peroxisomes to form or maintain themselves so that functional defects are present in more than one enzyme of this organelle. The genes responsible for the failure in the metabolism of phytanic acid have been traced to the short arm of chromosome 10 10pterp11. The zellweger spectrum of pbds include related, but not more severe, disorders referred to as. Following genetic testing, he has been diagnosed with adult refsum s disease.
Refsums dis ease is a rare, autosomal recessive neurometabolic disease, characterised biochemically by accumulation of phytanic acid in blood and tissues. Adult refsum disease ard is a rare genetic disease that causes weakness or numbness of the hands and feet peripheral neuropathy. Cochlear implantation in refsum disease with facial nerve. It is a neurological disorder mainly caused by the deposition of phytanic acid in different tissues of human body. He initially chose the name heredoataxia hemeralopica polyneuritiformis, 1 subsequently amending this to heredopathia atactica polyneuritiformis. Refsum disease nord national organization for rare disorders. Therefore, refsum disease can be confirmed by a simple blood test that measures the levels of phytanic acid. Molecular techniques then afford the identification of specific mutations in genes encoding the enzymes responsible for bile acid synthesis. Pdf refsum disease is a rare autosomal recessive error of lipid metabolism. Zellweger syndrome, neonatal adrenoleukodystrophy, infantile refsum disease and rhizomelic chondrodysplasia punctata are progressive disorders characterized by loss of multiple peroxisomal metabolic functions. This in turn can be due to deficiencies of phytanoylcoa hydroxylase chromosome 10 or peroxin7 chromosome 6. Refsum disease is inherited as an autosomal recessive trait, the gene. Arginine improves peroxisome functioning in cells from.
Infantile refsum disease is a peroxisomal biogenesis disorder. Ird is associated with deficient phytanic acid catabolism, as is adult refsum disease, but they are different. Bakker1 1 systems medicine of metabolism and signalling, laboratory of. 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.
Besides retinal degeneration or retinal dystrophy associated with adult onset. 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. 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 genetic and rare diseases information center. It is inherited in an autosomal recessive manner and frequently causes signs and symptoms. May 23, 2019 refsum disease is a recessive disorder characterized by defective peroxisomal alphaoxidation of phytanic acid. The diagnosis of refsum disease is suspected on the basis of clinical findings and a plasma phytanic acid concentration greater than 200 moll in most affected individuals.
It is one of several disorders named after norwegian neurologist sigvald bernhard refsum 19071991. Mutations in the phyh gene have been found to cause more than 90 percent of all cases of refsum disease. It differs from lateronset refsum disease see chapter 7, a singleenzyme peroxisomal disorder. In addition, most known cases of refsum disease result from defects in a protein known as phytanoylcoa hydroxylase, or pahx. This article describes two siblings with infantile refsum disease ird whose initial presentation was that of malabsorption and mimicked a.
A variant of this disease that appears in children has been described. Our collaborative network of clinicians, researchers, patients and supporters are in search of better therapeutic methods and ultimately a cure donations can made here or sent to the address below. Liver and kidney disease chondroplasia punctata xray findings of scattered calcification at the end of the long bones and knee children with neonatal adrenoleukodystrophy and infantile refsum disease have many of the same features seen in zellweger syndrome. 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.
They form part of cell walls and constitute cell storage material. As a result, toxic levels of phytanic acid build up in the brain, blood, and other tissues. Nathalie nadal, marieodile rolland, christine tranchant, laurence reutenauer, gabor gyapay, jeanmarie warter, jeanlouis mandel, michel k. May 23, 2019 refsum disease rd is a neurocutaneous syndrome that is characterized biochemically by the accumulation of phytanic acid in plasma and tissues. This xlinked disease is caused by inactivation of the lysosomal enzyme. Refsums disease is an inherited disorder of fatty acid oxidation. Know what is refsum disease, its causes, symptoms, treatment, complications, and prognosis. Infantile refsum disease ird, is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the zellweger spectrum.
It is different from the straight chain fatty acid shown above in that it has branches of carbon groups off the main carbon chain branches are colored. Refsum s disease is caused by defective alpha oxidation of phytanic acid 3,7,11,15 tetramethylhexadecanoic acid, a branched. Allen ginsberg, bill morgan in pdf format, in that case you 26 jun gmtread and download howl kaddish and other poems allen ginsberg free ebooks gepgrafija pdf format mercedes benz sl repair the pdf specification does have a limit of what nominally appears to be x for a page. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems that develop later in life. The age at onset of clinical signs and symptoms varies from early childhood to the fifth decade. Jun 26, 2006 the main treatment for adult refsum s disease is dietary and requires the expertise of a dietitian. Martin fromadelaide hospital, dublin summary thecase reports ofthree cases ofrefsums syndrome are presented, and the under lying metabolic abnormality discussed. Identification of pex7 as the second gene involved in refsum. Without proper treatment, complications related to gerd can impede normal development and can lead to multiple hospitalizations and medical conditions. It is not intended to supplement appropriate medical care, but instead to complement that care with guidance in practical issues facing patients and parents. Pdf refsum disease, peroxisomes and phytanic acid oxidation.
Brunelle2 refsum disease rd is a rare autosomal recessive disorder characterized by an accumulation of phytanic acid. Refsum s disease is caused by faulty enzymes during the alphaoxidation of phytanic acid resulting in buildup of phytanic acid and its unsaturated fatty acid derivatives in the plasma and tissues. In most patients with rd, disease causing mutations in the phyh gene have been identified, but, in a subset, no mutations could be found, indicating that the condition is genetically heterogeneous. 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.
Livingdonor liver transplantation from a heterozygous. 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. Refsum disease information page national institute of. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems which develop later in life.
Computed tomographic ct and magnetic resonance mr images in 24 patients with symptoms mean age at time of imaging, 37 years. Jan, 2016 the term ichthyosis describes a generalized disorder of cornification characterized by scaling andor hyperkeratosis of different skin regions. Refsums disease is characterised by phytanic acid accumulation in the blood. A 42yearold woman presented with a 2month history of imbalance. Refsum disease is an autosomal recessive neurological disease that results in the overaccumulation of phytanic acid in cells and tissues. Reversible vestibular neuropathy in adult refsum disease. The casereports of three cases of refsum s syndrome are presented, and the underlying metabolic abnormality discussed. However, the skin is more frequently affected in neuromuscular disorders and deserves more attention than so far acknowledged. Ataxia with loss of purkinje cells in a mouse model for. Patients with this disease may be hospitalized with faradvanced central nervous system cns lesions or may complain of symptoms similar to those of certain psychiatric disorders, possibly leading to a wrong diagnosis. Two patients died, and imaging findings were compared with. First, the patient should eat sufficiently well to prevent loss of weight. The activity of phytanic acid oxidase is low in infantile and adult refsum s disease, and in the cerebro. Following genetic testing, he has been diagnosed with adult refsums disease.
Pbds are part of a larger group of disorders called the leukodystrophies. Nov 04, 2016 refsum disease its a genetical disorder which is autosomal recessive phytanoylcoahydroxylase is the enzyme location of this enzyme is chromosome 10p slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. The plasma of patients with the infantile but not the adult form of refsum s disease contains increased amounts of pipecolic acid and of at least two abnormal bile acids, one of which has been. Jun 26, 2006 welcome to the adult refsum s disease website it contains. Pdf refsum disease was first recognized as a distinct disease entity by sigvald refsum in the. Refsums diseaseuse of the intestinal lipase inhibitor. However, the power of the prediction and the value of these metabolic changes in relation to the pathogenesis of phytanate in patients with rd require. These diseases are inherited in an autosomal recessive manner, are caused by defects in the import of peroxisomal matrix proteins and are referred to as the peroxisome biogenesis. We identified 53 metabolites that were predicted to discriminate between healthy and refsum disease patients, several of which with a link to amino acid metabolism. Refsum disease is an inherited condition that causes vision loss, loss of smell anosmia, and a variety of other signs and symptoms. Ataxia with loss of purkinje cells in a mouse model for refsum disease sacha ferdinandussea,1,2, anna w. Infantile refsum disease an overview sciencedirect topics. Enable javascript to view the expandcollapse boxes. Both feet showed foreshortening of the fourth digit.
Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. These mutations alter the structure or production of phytanoylcoa hydroxylase, which reduces the enzymes activity. The effect of treatment with a lowphytanic acid diet in one case is described. Furthermore, specific peptides are involved in the processes that lead to disease development, and their presence could indicate specific diseases, that is serve as disease biomarkers 4447. A metabolic disease characterized by anosmia, cataract, earlyonset retinitis pigmentosa and possible. Failure to recognize ird in the firstborn child precluded proper genetic counseling and prenatal diagnosis in subsequent pregnancies and also caused considerable delay in diagnosing ird in the second child. Research open access arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder kevin berendse1,2, merel s ebberink1, lodewijk ijlst1, bwee tien.
Thomas klockgether, in textbook of clinical neurology third edition, 2007. 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 the vision loss associated with refsum disease is caused by an eye disorder called retinitis pigmentosa. Infantile refsum disease is the mildest of a group of disorders known as peroxisome biogenesis disorders, zellweger syndrome spectrum pbdzss. Refsum disease is a rare genetic disease that currently has no cure. Refsum disease is a rare autosomal recessive disorder characterized biochemically by accumulation of phytanic acid in blood and tissues, including fat and neurons. Childhood cerebral xlinked ald is the most severe phenotype, resulting in rapid neurologic deterioration and early death. 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. Alans blood biochemistry is normal apart from a plasma phytanic acid level of 850 moll. Using this approach, 6 of the 7 known genetic defects that are causes of progressive cholestatic liver disease, syndromes. Refsum disease is a recessive disorder characterized by defective peroxisomal alphaoxidation of phytanic acid. He has recently been complaining of numb feet, scaly, itchy skin and deteriorating vision. Defects in bile acid biosynthesisdiagnosis and treatment. This disorder affects the retina, the lightsensitive layer at the back of the eye.
The peroxisome is responsible for the breakdown of certain branched chain fatty acids. Refsum disease is caused by a faulty gene phyh or pex7 which results in the lack of an enzyme that doesnt allow the oxidation of a fatty acid called phytanic acid and it accumulates in the blood and fat tissues. The vision loss associated with refsum disease is caused by an eye disorder called retinitis pigmentosa. Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. A variant of this disease that occurs in children is called infantile refsum disease. Infantile refsum disease is part of the zellweger spectrum of disorders zss of peroxisome biogenesis. 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. Refsum disease heredopathia atactica polyneuritiformis is an autosomal recessive disorder named for sigvald refsum who initially characterized the cardinal clinical features of this disease that results from defects in fatty acid metabolism. Refsum disease is named after a norwegian neurologist sigvald bernhard refsum. A thorough evaluation of the skin and its appendages is frequently outside the area of expertise of the neurologist who deals with neuromuscular disorders. Refsums disease dietetic and nutrition case studies. May 20, 2015 infantile refsum disease is the mildest of a group of disorders known as peroxisome biogenesis disorders, zellweger syndrome spectrum pbdzss.
Zellweger syndromespectrumpex17related whatiszellwegersyndromespectrumpex17related. Refsum disease is characterized by anosmia and earlyonset retinitis. Vision loss occurs as the lightsensing cells of the. Mutations in a broad group of genes related to keratinocyte differentiation and epidermal barrier function have been demonstrated to play a causative role in disease development. Role of molecular testing in the multidisciplinary diagnostic. Refsum disease is characterized by anosmia and earlyonset retinitis pigmentosa, which are both universal findings with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. Refsum disease heredopathia atactica polyneuritiformis was first described in 1946 and is a rare recessively inherited metabolic disease affecting phytanic acid metabolism. The pathophysiology of refsum disease is characterized by accumulation of phytanic acid in plasma and tissues 200. Fabry disease is one of several wellcharacterized lipidoses with a renal phenotype. Onset of symptoms ranges from age seven months to older than age 50 years. 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. Refsum disease 266500 phyh 602026 deafness, ataxia, retinitis pigmentosa, ichthyosis, heart failure. She had longstanding bilateral hearing loss, retinitis pigmentosa, anosmia, and numbness in both feet.
Patients affected with refsum disease rd have elevated levels of phytanic acid due to a deficiency of the peroxisomal enzyme phytanoylcoa hydroxylase phyh. Dick and others published hypokalemia in acute refsum s disease find, read and cite all the research you need on researchgate. Techniques in diagnostic human biochemical genetics. Gastroesophageal reflux disease gerd is a serious phenomenon in pediatric health care.
Their biosynthesis and metabolism play key roles in faraway topics such as biofuel production third. Wegrzyn1,2, katharina herzog3,4, albert gerding1,5, marcel kwiatkowski6,7, justina c. 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. Refsum disease is characterized by an accumulation of phytanic acid in the plasma and tissues. Magnetic resonace imaging findings in a case of infantile.
1010 713 569 1281 1026 640 962 1430 19 1352 1304 267 328 827 1336 917 929 1222 1177 170 1025 1115 1147 1460 482 1227 64 7 675 1284 1405