The early presentation raises the possibility of in utero exposure to phytanate. [ncbi.nlm.nih.gov]

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. [doi.org]

• Splenomegaly

  After 6 months, he had poor visual contact, apparent hypoacusia, muscle hypotonia, nystagmus, and splenomegaly. [pediatrics.aappublications.org]

• Hemophilia A

  […] disease Glycogen storage disease Goldenhar syndrome (hemifacial microsomia) Gorlin syndrome (basal cell carcinoma, nevi) Hallermann Streiff syndrome Hearing problems Heart conditions (congenital heart, adult cardiovascular) Hemochromatosis (iron overload) Hemophilia [kumc.edu]

• Developmental Delay

  He presented unusually early, hypotonia and developmental delay being apparent by 7 months. [ncbi.nlm.nih.gov]

  […] acid, cholesterol, very long-chain fatty acids, dihydroxycholestanoic acid, trihydroxycholestanoic acid, and pipecolic acid Clinical features: Growth and developmental delay, peripheral neuropathy, hypotonia, deafness, facial dysmorphism, retinopathy, [merckmanuals.com]

  We report the case of a 6-year-old boy who presented with developmental delay, ataxia, hypotonia, areflexia, vision and hearing impairment, dysmorphism, and hepatomegaly. [thieme-connect.com]

• Progressive Dementia

  Discussion We report the very unusual case of a 72-year-old woman presenting with 2 years’ history of progressive dementia, walking problems, and diffuse leukoencephalopathy. [ncbi.nlm.nih.gov]

• Anosmia

  Besides tapetoretinal degeneration, additional symptoms are anosmia, skeletal malformations, chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, ichthyosis, and cardiac abnormalities. [ncbi.nlm.nih.gov]

  A rare autosomal recessive disorder in which an enzyme deficiency causes accumulation of phytanic acid in tissues, leading to retinitis pigmentosa, anosmia, and often ataxia, polyneuropathy, and other conditions. [medical-dictionary.thefreedictionary.com]

  Anosmia is also considered an early symptom [Wierzbicki et al 2002]. [refsumdisease.org]

  It is usually inherited and the condition can cause vision loss, and absence of smell (anosmia). It usually starts in early childhood to late adulthood. [wiki.ggc.usg.edu]

• Failure to Thrive

  Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. [ncbi.nlm.nih.gov]

  […] to thrive, postprandial vomiting Treatment: Not established, possible benefit from riboflavin Mevalonic aciduria — — Acatalasemia (115500) Catalase CAT (11p13)* Biochemical profile: Failure of tissue to cause hydrogen peroxide frothing Clinical features [merckmanuals.com]

  […] to thrive Cytogenetic testing for 17p13.3 microdeletion -- Dopa-responsive dystonia + - - + Onset in early childhood Symptoms worsen with fatigue and exercise Positive response to a trial of levodopa -- Treatment The most effective therapy in the classic [wikidoc.org]

  The patient was a 4-year-old girl with severe hearing and visual impairment, together with failure to thrive. 5 Subsequently, in 2005, the first case of living-donor liver transplantation (LDLT) in a mildly symptomatic 6-month-old infant who was the sibling [pediatrics.aappublications.org]

• Hepatomegaly

  Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. [ncbi.nlm.nih.gov]

  We report the case of a 6-year-old boy who presented with developmental delay, ataxia, hypotonia, areflexia, vision and hearing impairment, dysmorphism, and hepatomegaly. [thieme-connect.com]

  […] include rapid, jerky eye movements (nystagmus), floppy muscle tone (hypotonia) and lack of muscle coordination (ataxia), mental and growth retardation, mild abnormalities in the form and structure of the face (dysmorphia), enlargement of the liver (hepatomegaly [sharecare.com]

  On physical examination, the skin was pale, there was hepatomegaly, a 2/6° of systolic murmur, and strabismus. There was generalized hypotonia with stereotypic movements such as shaking and bending forward. [ajnr.org]

• Liver Dysfunction

  The progressive pathologic changes and severe neurologic, together with liver, dysfunction are inevitable. 1, 2, 4 However, according to recent reports, the optimal treatment regimen, including dietary restriction, showed the PA to decrease to normal [pediatrics.aappublications.org]

• Hearing Impairment

  We report the case of a 6-year-old boy who presented with developmental delay, ataxia, hypotonia, areflexia, vision and hearing impairment, dysmorphism, and hepatomegaly. [thieme-connect.com]

  The visual and hearing impairments are less responsive to treatment. [ 11 ] Genetic counselling [ 5 ] Refsum's disease is inherited in an autosomal recessive manner. [patient.info]

  Her hospital stay was complicated by progressive impairment of vision and hearing loss. Her lab values showed elevated levels of phytanic acid. [path.upmc.edu]

• Progressive Hearing Loss

  […] visual loss ears: progressive hearing loss heart: arrhythmias Age at First Appearance: neurologic findings usually detected during the first or second decade; skin findings usually later Longterm Course: onset is insidious; neurologic changes progressive [firstskinfoundation.org]

  Case Details A 6-year- old child with progressive hearing loss wasbrought for consultation. History revealed that the child was born normal butprogressively developed loss of hearing and loss of smell. [namrata.co]

• Night Blindness

  The authors report the case of a 14-year-old girl diagnosed because of night blindness. They treated her with a phytanic acid-poor diet and extracorporeal lipid apheresis. They used different methods over a 30-month period. [ncbi.nlm.nih.gov]

  Typically, individuals with adult Refsum's disease experience night-blindness years before the progressive chnages changes of constricted visual fields and decreased central visual acuity appear. [refsumdisease.org]

  The elder brother, aged 43, was myopic and developed night blindness and peripheral visual field loss at six years of age. [doi.org]

  Night blindness may be an early symptom. Diagnosis is made by demonstrating elevated plasma levels of phytanic acid or reduced phytanic acid oxidase activity in cultured fibroblasts. [aao.org]

  The disease usually begins in late childhood with increasing night blindness due to degeneration of the retina (retinitis pigmentosa) and loss of the sense of smell (anosmia). [web.archive.org]

• Visual Impairment

  Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date. [ncbi.nlm.nih.gov]

• Visual Impairment

  Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date. [ncbi.nlm.nih.gov]

• Alopecia

  PDH enzymatic activity in cultured fibroblasts -- Arginase deficiency + - - - Hyperammonemia Encephalopathy Respiratory alkalosis Elevated ammonia level Elevated arginine level -- Holocarboxylase synthetase deficiency - + - - Ketoacidosis Dermatitis Alopecia [wikidoc.org]

  Win32 Error Code = 87 Aarskog syndrome Achondroplasia Achromatopsia Acoustic neuroma (and benign cranial nerve tumors) Adrenal hyperplasia Adrenoleukodystrophy Agenesis of corpus callosum Aicardi syndrome Alagille syndrome Albinism (& (hypopigmentation) Alopecia [kumc.edu]

• Large Anterior Fontanels

  Craniofacial abnormalities reported include: high forehead; hypoplastic supraorbital ridges; epicanthal folds; midface hypoplasia; and large anterior fontanelle. [ncbi.nlm.nih.gov]

  FIGURE 1 Facial dysmorphism (high forehead, large anterior fontanelle, hypoplastic supraorbital ridges, epicanthal folds, and deformed earlobes) in the patient with IRD. [pediatrics.aappublications.org]

• Suggestibility

  The anti-metabolite hypothesis suggests that an accumulation of phytanic acid in membranes may interfere with vitamin E function. [ncbi.nlm.nih.gov]

• Psychomotor Retardation

  We describe an 18-year-old patient with psychomotor retardation and abnormally short metatarsi and metacarpals but no other signs of classic Refsum disease. [ncbi.nlm.nih.gov]

  Severe, infantile-onset retinal degeneration is associated in this disorder with hypotonia, psychomotor retardation, seizures, characteristic facies, renal cysts, and hepatic interstitial fibrosis. Death usually occurs in infancy. [aao.org]

  He had been followed since birth because of a large anterior fontanelle (8 × 8 cm), early infantile-onset transaminitis, psychomotor retardation, and facial dysmorphism ( Fig 1 ). [pediatrics.aappublications.org]

  This condition maps to the same locus on chromosome 10p as PAHX and probably represents an allele‐specific variant. 20 Further evidence for this comes from a recent report of an 18‐year old patient with psychomotor retardation and abnormally short metatarsals [qjmed.oxfordjournals.org]

• Ataxia

  A diet low in phytanic acid ameliorates polyneuropathy and ataxia and slows or even stops the other manifestations. [ncbi.nlm.nih.gov]

  Signs and symptoms include neurologic damage, cerebellar degeneration, and neuropathy An autosomal recessive familial disorder that usually presents in childhood with polyneuropathy; sensorineural hearing loss; ichthyosis; ataxia; retinitis pigmentosa [icd9data.com]

  Indeed, several patients have been described lacking cerebellar ataxia. Accumulation of phytanic acid is not unique to Refsum disease. [ommbid.mhmedical.com]

• Cerebellar Ataxia

  Major diagnostic clinical findings include retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, increased cerebrospinal fluid protein without pleocytosis, nerve deafness, and cardiac involvement. [ncbi.nlm.nih.gov]

  Indeed, several patients have been described lacking cerebellar ataxia. Accumulation of phytanic acid is not unique to Refsum disease. [ommbid.mhmedical.com]

  Overview Refsum disease is a rare, autosomal recessive disorder characterized clinically by retinitis pigmentosa, peripheral polyneuropathy, and cerebellar ataxia and biochemically by accumulation in tissues of the dietary branched-chain fatty acid, phytanic [medlink.com]

• Peripheral Neuropathy

  In people with Refsum disease, phytanic acid can accumulate, leading to neurological problems vision loss, hearing loss, peripheral neuropathy, and neurodegeneration of the central nervous system. A. [chegg.com]

  An atypical case of Refsum disease is reported together with the peripheral nerve morphological data. The body fluids must be assayed for phytanic acid whenever an atypical chronic peripheral neuropathy is observed. [ncbi.nlm.nih.gov]

  With treatment, symptoms of peripheral neuropathy and ichthyosis generally disappear. But, while treatment may prevent further deterioration of vision and hearing, it can’t undo damage to vision and hearing that has already occurred. [blog.imwithoutstress.com]

• Nystagmus

  IRD patients present with multiple clinical manifestations, including: retinitis pigmentosa; nystagmus; sensorineural hearing loss; mental and developmental delays; neuromotor defects; and cerebral ataxia. [ncbi.nlm.nih.gov]

  Refsum disease - a rare hereditary degenerative disorder characterized by retinitis pigmentosa, demyelinating polyneuropathy, deafness, nystagmus, and cerebellar signs. Synonym(s): heredopathia atactica polyneuritiformis ; Refsum syndrome [medical-dictionary.thefreedictionary.com]

  Other symptoms may include rapid, jerky eye movements (nystagmus), floppy muscle tone (hypotonia) and lack of muscle coordination (ataxia), mental and growth retardation, mild abnormalities in the form and structure of the face (dysmorphia), enlargement [sharecare.com]

  Case Reports Patient 1 A 2-year 9-month-old girl with nystagmus, visual and hearing impairment, and developmental delay was evaluated for the possibility of multisystem genetic disorder. [ajnr.org]

• Neurologic Manifestation

  Disease definition Refsum disease (RD) is a very rare, clinically variable, multisystemic metabolic disease, characterized by anosmia, early-onset retinitis pigmentosa and possible neurological manifestations, including neuropathy, and cerebellar ataxia [orpha.net]

  The cardinal neurological manifestations of the disease include a demyelinating neuropathy, pes cavus, cerebellar ataxia, sensorineural deafness, anosmia and cranial nerve involvement (5).There may be marked nerve hypertrophy. [path.upmc.edu]

  Differential diagnosis Refsum's disease must be differentiated from other diseases that cause neurological manifestations in infants. [wikidoc.org]

  The cardinal neurological manifestations of the disease include a demyelinating neuropathy, pes cavus, cerebellar ataxia, sensorineural deafness, anosmia and cranial nerve involvement. 7 There may be marked nerve hypertrophy. [qjmed.oxfordjournals.org]

A metabolic workup disclosed very high plasma phytanic acid level (458 μmol/L; control Genetic analysis of the PHYH gene revealed a novel homozygous mutation in exon 1, c.42-60dup, a frameshift mutation resulting in a premature stop codon at position [ncbi.nlm.nih.gov]

Additional preoperative workup was performed. Funduscopy revealed retinitis pigmentosa ( Fig 3 ). [pediatrics.aappublications.org]

• Abnormal ECG

  Cardiomyopathy and conduction abnormalities. ECG changes are present. Ichthyosis, hyperkeratosis plantaris and palmaris may be seen. [patient.info]

Treatment for RD is aimed at lowering the serum levels of phytanic acid. [doi.org]

Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date. [ncbi.nlm.nih.gov]

Treatment should be instituted as early as possible and continued for life. [ommbid.mhmedical.com]

Is there any treatment? The primary treatment for ARD is to restrict or avoid foods that contain phytanic acid, including dairy products; beef and lamb; and fatty fish such as tuna, cod, and haddock. [web.archive.org]

Refsum's disease phytanic acid diet peroxisome metabolic disease neuroophthalmology prognosis Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright [dx.doi.org]

Prognosis Prognosis in the absence of treatment is generally poor. Severe cases or late diagnosis may be life-threatening. The main cause of death is arrhythmia and heart failure. Expert reviewer(s): Pr B.T. [Bwee Tien] POLL-THE - Pr R.J.A. [orpha.net]

What is the prognosis of Refsum disease? Prognosis of Refsum disease varies dramatically. Strict adherence to a dietary regimen (see treatment, below) can cause the neurological symptoms to arrest, and nerve response can improve. [ulf.org]

Etiology RD is caused by mutations in the PHYH gene (10p13) in more than 90% of cases, and mutations in the PEX7 gene (6q21-q22.2) in less than 10%. These genes are involved in lipid metabolism and protein transport. [orpha.net]

ETIOLOGY: Refsum's disease is a rare autosomal recessive condition first characterized by Sigvald Refsum in 1945 (1). [path.upmc.edu]

Ichthyosis is an unusual symptom. [14, 15] Etiology Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase ( PHYH ) and the PTS2 receptor ( PEX7 ) genes. This disorder is inherited in an autosomal recessive mode. [emedicine.com]

Summary Epidemiology About 60 cases have been reported worldwide. Prevalence rates are not known but the disorder may be underdiagnosed. Prevalence has been estimated to be 1/1,000,000 in the United Kingdom. Males and females are affected equally. [orpha.net]

Epidemiology Frequency Refsum disease is rare, with just 60 cases published worldwide. Race No racial predominance is reported. Sex Only male cases were reported initially; however, now, neither sex predominates. [emedicine.com]

Infantile Refsum disease has clinical features and a pathophysiology distinct from classic Refsum disease, despite occasionally presenting for examination later in life. [ncbi.nlm.nih.gov]

Until 1963 the pathogenesis and pathophysiology of Refsum disease was not known. [medlink.com]

Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives. Dev Disabil Res Rev. 2013 Jun. 17(3):187-96. [Medline]. Aubourg P, Wanders R. Peroxisomal disorders. Handb Clin Neurol. 2013. 113:1593-609. [Medline]. [emedicine.com]

Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date. [ncbi.nlm.nih.gov]