This in turn can be due to deficiencies of phytanoylcoa hydroxylase chromosome 10 or peroxin7 chromosome 6. Reversible vestibular neuropathy in adult refsum disease. He has recently been complaining of numb feet, scaly, itchy skin and deteriorating vision. Nathalie nadal, marieodile rolland, christine tranchant, laurence reutenauer, gabor gyapay, jeanmarie warter, jeanlouis mandel, michel k. Pbdzss is a group of inherited genetic disorders that damage the white matter of the brain and affect motor movements. Refsum disease is a rare disorder of lipid metabolism that is inherited as a recessive trait. Refsums disease is characterised by phytanic acid accumulation in the blood.
Pdf refsum disease, peroxisomes and phytanic acid oxidation. Refsums diseaseuse of the intestinal lipase inhibitor. The gene locus is on chromosome 7q21q22 and transmission of the disorder. Bakker1 1 systems medicine of metabolism and signalling, laboratory of. It is almost exclusively of exogenous origin and is delivered mainly from dietary plant chlorophyll and, to a lesser extent, from.
Using this approach, 6 of the 7 known genetic defects that are causes of progressive cholestatic liver disease, syndromes. 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. As a result, toxic levels of phytanic acid build up in the brain, blood, and other tissues. Cochlear implantation in refsum disease with facial nerve. 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. About 60 cases of refsum disease rd have been reported worldwide. Refsum disease information page national institute of.
Two patients died, and imaging findings were compared with. Childhood cerebral xlinked ald is the most severe phenotype, resulting in rapid neurologic deterioration and early death. 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. The zellweger spectrum of pbds include related, but not more severe, disorders referred to as. Infantile refsums disease refsoomz is an inherited metabolic disorder that is characterized by the abnormal accumulation of phytanic acid in blood plasma and tissues. 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. 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. 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. Jun 26, 2006 welcome to the adult refsum s disease website it contains. Therefore, refsum disease can be confirmed by a simple blood test that measures the levels of phytanic acid. They form part of cell walls and constitute cell storage material. Fabry disease is one of several wellcharacterized lipidoses with a renal phenotype. 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. First, the patient should eat sufficiently well to prevent loss of weight.
Classic refsum disease the medical biochemistry page. Jun 26, 2006 the main treatment for adult refsum s disease is dietary and requires the expertise of a dietitian. The genes responsible for the failure in the metabolism of phytanic acid have been traced to the short arm of chromosome 10 10pterp11. 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 heredopathia atactica polyneuritiformis was first described in 1946 and is a rare recessively inherited metabolic disease affecting phytanic acid metabolism. Refsum disease genetic and rare diseases information. 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. 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. Refsum disease is a rare genetic disease that currently has no cure. The peroxisome is responsible for the breakdown of certain branched chain fatty acids. It is one of several disorders named after norwegian neurologist sigvald bernhard refsum 19071991. 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. It is a neurological disorder mainly caused by the deposition of phytanic acid in different tissues of human body. Thomas klockgether, in textbook of clinical neurology third edition, 2007.
Refsums dis ease hereditary motor and sensory neuropathy type iv is a rare autosomal recessive condition first characterized by sigvald refsum in 1945. Infantile refsum disease is part of the zellweger spectrum of disorders zss of peroxisome biogenesis. Adult refsum disease ard is a rare genetic disease that causes weakness or numbness of the hands and feet peripheral neuropathy. It differs from lateronset refsum disease see chapter 7, a singleenzyme peroxisomal disorder. 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. Molecular techniques then afford the identification of specific mutations in genes encoding the enzymes responsible for bile acid synthesis. Infantile refsum disease is the mildest of a group of disorders known as peroxisome biogenesis disorders, zellweger syndrome spectrum pbdzss. Refsums disease dietetic and nutrition case studies. A 42yearold woman presented with a 2month history of imbalance. Both feet showed foreshortening of the fourth digit. Infantile refsum disease is a peroxisomal biogenesis disorder. Refsum disease is characterized by anosmia and earlyonset retinitis. Refsum disease genetic and rare diseases information center. Computed tomographic ct and magnetic resonance mr images in 24 patients with symptoms mean age at time of imaging, 37 years.
Ataxia with loss of purkinje cells in a mouse model for refsum disease sacha ferdinandussea,1,2, anna w. Refsums disease is an inherited disorder of fatty acid oxidation. Mutations in the phyh gene have been found to cause more than 90 percent of all cases of refsum disease. 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. 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. Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. The effect of treatment with a lowphytanic acid diet in one case is described. 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. Infantile refsum disease information page national. Refsum disease is a recessive disorder characterized by defective peroxisomal alphaoxidation of phytanic acid. Besides retinal degeneration or retinal dystrophy associated with adult onset. Dick and others published hypokalemia in acute refsum s disease find, read and cite all the research you need on researchgate. Following genetic testing, he has been diagnosed with adult refsum s disease. Brunelle2 refsum disease rd is a rare autosomal recessive disorder characterized by an accumulation of phytanic acid.
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 characterized by anosmia and earlyonset retinitis pigmentosa, which are both universal findings with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. Ird is associated with deficient phytanic acid catabolism, as is adult refsum disease, but they are different. Coa hydroxylase that is involved in the oxidation of phytanic acid. Onset of symptoms ranges from age seven months to older than age 50 years. 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.
Refsum disease is named after a norwegian neurologist sigvald bernhard refsum. May 23, 2019 refsum disease is a recessive disorder characterized by defective peroxisomal alphaoxidation of phytanic acid. 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. Patients affected with refsum disease rd have elevated levels of phytanic acid due to a deficiency of the peroxisomal enzyme phytanoylcoa hydroxylase phyh. 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. 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. 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 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. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems which develop later in life. Following genetic testing, he has been diagnosed with adult refsums disease. Find, read and cite all the research you need on researchgate. Magnetic resonace imaging findings in a case of infantile. Refsum disease, infantile form genetic and rare diseases. Refsum disease is inherited as an autosomal recessive trait, the gene.
The casereports of three cases of refsum s syndrome are presented, and the underlying metabolic abnormality discussed. Defects in bile acid biosynthesisdiagnosis and treatment. This xlinked disease is caused by inactivation of the lysosomal enzyme. Refsum disease is characterized by an accumulation of phytanic acid in the plasma and tissues. 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. Gastroesophageal reflux disease gerd is a serious phenomenon in pediatric health care. Pbds are part of a larger group of disorders called the leukodystrophies. Wegrzyn1,2, katharina herzog3,4, albert gerding1,5, marcel kwiatkowski6,7, justina c. Infantile refsum disease ird, is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the zellweger spectrum. Refsum disease 266500 phyh 602026 deafness, ataxia, retinitis pigmentosa, ichthyosis, heart failure.
Zellweger syndromespectrumpex17related whatiszellwegersyndromespectrumpex17related. Refsum disease nord national organization for rare. The age at onset of clinical signs and symptoms varies from early childhood to the fifth decade. Also termed heredopathia atactica polyneuritiformis, it was first identified as a clinical entity by refsum in the 1940s. Refsum s disease is a rare, autosomal recessive disorder due to mutations in the gene encoding phytanoyl. Identification of pex7 as the second gene involved in refsum.
May 20, 2015 infantile refsum disease is the mildest of a group of disorders known as peroxisome biogenesis disorders, zellweger syndrome spectrum pbdzss. 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. 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. She had longstanding bilateral hearing loss, retinitis pigmentosa, anosmia, and numbness in both feet. Zellweger syndrome, neonatal adrenoleukodystrophy, infantile refsum disease and rhizomelic chondrodysplasia punctata are progressive disorders characterized by loss of multiple peroxisomal metabolic functions. Arginine improves peroxisome functioning in cells from. Livingdonor liver transplantation from a heterozygous. 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. 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. Symptoms include retinitis pigmentosa, loss of hearing, loss of smell, and more. Vision loss occurs as the lightsensing cells of the. 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.
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. Infantile refsums disease phytanic acid storage disease. A metabolic disease characterized by anosmia, cataract, earlyonset retinitis pigmentosa and possible. 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. A variant of this disease that appears in children has been described. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems that develop later in life. 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. May 23, 2019 refsum disease rd is a neurocutaneous syndrome that is characterized biochemically by the accumulation of phytanic acid in plasma and tissues. 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. He initially chose the name heredoataxia hemeralopica polyneuritiformis, 1 subsequently amending this to heredopathia atactica polyneuritiformis.
Refsums diseaseuse of the intestinal lipase inhibitor, orlistat, as. 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. A variant of this disease that occurs in children is called infantile refsum disease. The pathophysiology of refsum disease is characterized by accumulation of phytanic acid in plasma and tissues 200. About 30 mutations in this gene have been identified. However, the skin is more frequently affected in neuromuscular disorders and deserves more attention than so far acknowledged. A variant that occurs in children is called infantile refsum disease ird. 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. 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. Techniques in diagnostic human biochemical genetics. It is inherited in an autosomal recessive manner and frequently causes signs and symptoms. A thorough evaluation of the skin and its appendages is frequently outside the area of expertise of the neurologist who deals with neuromuscular disorders. Infantile refsum disease is the mildest of a group of disorders known as. Enable javascript to view the expandcollapse boxes.
The vision loss associated with refsum disease is caused by an eye disorder called retinitis pigmentosa. Know what is refsum disease, its causes, symptoms, treatment, complications, and prognosis. Using this model, we investigated the metabolic phenotype of refsum disease at the genome. Information for patients, their families, and helpers what adult refsum s disease is, and what to do if you are affected by it. Previously, surgical intervention was limited to one technique, nissen fundoplication. 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. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. A common branched chain fatty acid, phytanic acid, is shown below. In addition, most known cases of refsum disease result from defects in a protein known as phytanoylcoa hydroxylase, or pahx. Refsum disease is an autosomal recessive neurological disease that results in the overaccumulation of phytanic acid in cells and tissues. Pdf refsum disease was first recognized as a distinct disease entity by sigvald refsum in the. Refsum disease is an inherited condition that causes vision loss, loss of smell anosmia, and a variety of other signs and symptoms. Infantile refsum disease is a rare inborn error of phytanic acid metabolism.
This article describes two siblings with infantile refsum disease ird whose initial presentation was that of malabsorption and mimicked a. Martin fromadelaide hospital, dublin summary thecase reports ofthree cases ofrefsums syndrome are presented, and the under lying metabolic abnormality discussed. Jan, 2016 the term ichthyosis describes a generalized disorder of cornification characterized by scaling andor hyperkeratosis of different skin regions. Human genome landmarks oak ridge national laboratory. Ichthyosis may be classified in syndromic or nonsyndromic forms based on.
Refsum disease is a rare autosomal recessive disorder characterized biochemically by accumulation of phytanic acid in blood and tissues, including fat and neurons. Infantile refsum disease an overview sciencedirect topics. 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. This disorder affects the retina, the lightsensitive layer at the back of the eye. It is not intended to supplement appropriate medical care, but instead to complement that care with guidance in practical issues facing patients and parents. The activity of phytanic acid oxidase is low in infantile and adult refsum s disease, and in the cerebro. Two brothers with refsums disease who experienced progressive symptoms despite optimal diet and plasmapheresis were. Adult refsums disease information for patients the facts.
Role of molecular testing in the multidisciplinary diagnostic. Iatrogenic phospholipidosis mimicking fabry disease. Without proper treatment, complications related to gerd can impede normal development and can lead to multiple hospitalizations and medical conditions. Refsum disease nord national organization for rare disorders. Their biosynthesis and metabolism play key roles in faraway topics such as biofuel production third. Refsum disease is a peroxisomal disorder caused by the impaired. Refsums dis ease is a rare, autosomal recessive neurometabolic disease, characterised biochemically by accumulation of phytanic acid in blood and tissues. Localization of refsum disease with increased pipecolic. 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. These mutations alter the structure or production of phytanoylcoa hydroxylase, which reduces the enzymes activity. Peroxisome biogenesis disorders, in turn, are part of a larger group of disorders called leukodystrophies. Cochlear implantation in refsum disease with facial nerve en. Alans blood biochemistry is normal apart from a plasma phytanic acid level of 850 moll. 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.
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