EMERGENCY:A patient with Refsum disease who develops rapid neurological worsening, cardiac arrhythmia, or acute episode of neurological deterioration requires urgent assessment. Plasma exchange (plasmapheresis) may be needed for acute phytanic acid crises. —call040-46324365immediately — 24 hours, 7 days— 24/7
Refsum Disease in Hyderabad: The Rare Inherited Neuropathy Where Stopping a Food Stops the Disease
Expert plasma phytanic acid measurement, PHYH and PEX7 gene sequencing, NCS / CSF / ECG / ophthalmological assessment, phytanic acid-restricted dietetic programme with Indian-recipe substitutions, plasma exchange for acute crises, cardiac arrhythmia surveillance, and family genetic counselling by the KIMS Neuroscience team at KIMS Neuroscience, Secunderabad, Hyderabad.
Refsum disease is an autosomal recessive peroxisomal disorder caused by mutations in PHYH (most cases) or PEX7, leading to deficient alpha-oxidation of phytanic acid and progressive accumulation of phytanic acid in the nervous system, retina, myocardium, and adipose tissue. The clinical tetrad is retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and raised CSF protein without pleocytosis (albumino-cytological dissociation), often accompanied by anosmia, sensorineural deafness, ichthyosis, and cardiac arrhythmia. Phytanic acid is derived ENTIRELY from dietary sources (ruminant fat and certain fish) — humans cannot synthesise it — which makes Refsum disease one of the few inherited neurological disorders where dietary restriction genuinely halts and partially reverses disease. KIMS provides phytanic acid testing, PHYH/PEX7 sequencing, an Indian-context dietitian-led restriction programme (avoiding ghee, paneer, and full-fat dairy), cardiac surveillance, and plasma exchange for acute crises and pre-operative preparation. Patients must avoid fasting, crash diets, and rapid weight loss, all of which mobilise stored phytanic acid and can precipitate acute neurological deterioration.
- The Refsum tetrad — and the CSF clue
- Diagnostic tetrad: (1) retinitis pigmentosa, (2) peripheral neuropathy, (3) cerebellar ataxia, (4) raised CSF protein WITHOUT pleocytosis — albumino-cytological dissociation. The combination is highly specific. Many patients also have anosmia, sensorineural deafness, ichthyosis, and short metacarpals/metatarsals. Any patient with RP + peripheral neuropathy must have plasma phytanic acid measured.
- Anosmia is universal — but never volunteered
- Anosmia is present from early life in almost every Refsum patient, so long-standing that they no longer notice or mention it. The clinician must ASK specifically about smell at the initial assessment. Anosmia + RP + peripheral neuropathy strongly points to Refsum disease — even before phytanic acid results return.
- Phytanic acid is exclusively dietary — diet genuinely halts disease
- Humans cannot synthesise phytanic acid. ALL the phytanic acid in the body comes from food — primarily ruminant fat (dairy and meat from cows, sheep, goats) and certain fish. This makes Refsum disease one of the few inherited neurological disorders where dietary restriction genuinely halts neurological progression and can partially reverse peripheral nerve dysfunction. Normal plasma phytanic acid <10 μmol/L; untreated Refsum typically >200 μmol/L.
- Indian dietary context — ghee, paneer, full-fat dairy
- In the Indian diet, the dominant phytanic acid sources are ghee, paneer, butter, full-fat milk, curd, and ruminant meat (mutton, beef). Vegetable oils (mustard, sunflower, groundnut) contain no phytanic acid. KIMS provides Indian-specific substitutions: mustard oil instead of ghee for cooking; tofu or chana paneer alternatives instead of dairy paneer; soya milk in place of cow / buffalo milk. A dietitian-led plan typically reduces plasma phytanic acid into the safe range over 4–8 weeks.
- Avoid fasting, crash diets, and rapid weight loss
- Phytanic acid is stored in adipose tissue. Fasting, crash diets, intercurrent illness, and bariatric surgery all rapidly mobilise stored phytanic acid into the circulation and can precipitate ACUTE neurological deterioration — sudden worsening of weakness, ataxia, cardiac arrhythmia. Patients are counselled to eat regular meals, never to skip food during illness, and to seek urgent medical advice with any acute weight loss.
- Plasmapheresis — reserved for acute severe manifestations
- Plasmapheresis/lipid apheresis is reserved mainly for acute severe manifestations such as cardiac arrhythmias or extreme weakness. It is not a routine treatment; dietary phytanic acid restriction is the cornerstone. Perioperative management should focus on avoiding fasting and catabolism; apheresis may be considered in selected high-risk situations. Surgical fasting and the catabolic stress of surgery mobilise stored phytanic acid, so KIMS coordinates the perioperative plan — glucose infusion, maintained caloric intake, avoidance of weight loss before and after surgery — with the dietetic team, adding apheresis for selected high-risk admissions.
- Cardiac surveillance — easy to miss, fatal when missed
- Phytanic acid accumulates in cardiac tissue. Cardiac arrhythmia and conduction disease are leading causes of death in untreated Refsum disease. Baseline ECG, echocardiogram, and Holter monitor at diagnosis; periodic surveillance lifelong; cardiology review for any palpitations or syncope. Cardiac involvement can precede severe neurological symptoms.
| Fact | Details |
|---|---|
| Mechanism | PHYH (commonest) or PEX7 mutations · Phytanic acid alpha-oxidation deficient · Phytanic acid accumulates in nervous tissue, retina, myocardium, adipose tissue |
| Tetrad | Retinitis pigmentosa · Peripheral neuropathy · Cerebellar ataxia · Raised CSF protein without pleocytosis (albumino-cytological dissociation) |
| Other features | Anosmia (universal, never volunteered) · Sensorineural deafness · Ichthyosis · Short 4th metacarpals/metatarsals · Cardiac arrhythmia / conduction disease |
| Diagnosis | Plasma phytanic acid (>10 μmol/L abnormal; Refsum typically >200) · PHYH and PEX7 gene sequencing · CSF protein · NCS · Ophthalmology, audiology, ECG/echo |
| Dietary treatment | Phytanic acid-restricted diet · Avoid ghee, paneer, full-fat dairy, ruminant meat · Mustard oil, tofu, soya milk substitutions · Dietitian-led plan · 4–8 weeks to normalise plasma |
| Avoid | Fasting · Crash diets · Rapid weight loss · Bariatric surgery without specialist input · Skipping meals during illness — all mobilise stored phytanic acid acutely |
| Plasmapheresis / lipid apheresis | Reserved mainly for acute severe manifestations — cardiac arrhythmias or extreme weakness · Not routine treatment · Perioperatively: avoid fasting and catabolism first; apheresis considered in selected high-risk situations |
About This Condition
Refsum Disease at a Glance
The essential facts that shape how Refsum disease is recognised, diagnosed, and managed at KIMS — from the PHYH-deficient peroxisomal biology and the dietary-only origin of phytanic acid, to the unique therapeutic feature that dietary restriction halts and partially reverses the disease, and the diagnostic tetrad of RP + neuropathy + ataxia + elevated CSF protein.
What it is
Refsum disease (heredopathia atactica polyneuritiformis) is a rare autosomal recessive peroxisomal disorder caused by deficiency of the enzyme phytanoyl-CoA hydroxylase (encoded by the PHYH gene, or less commonly the PEX7 gene). This enzyme catalyses the first step of the alpha-oxidation of phytanic acid — a branched-chain fatty acid derived exclusively from dietary sources (chlorophyll from plant foods and from the fat of ruminant animals and fish). Without PHYH, phytanic acid cannot be metabolised and accumulates in plasma, peripheral nerves, the retina, the cerebellum, the myocardium, skin, and bones.
The critical uniqueness: it is dietary and treatable
Refsum disease is one of very few inherited neurological conditions where a specific dietary change — restricting foods containing phytanic acid — prevents phytanic acid accumulation and halts or reverses neurological deterioration. The diet works because phytanic acid is derived entirely from exogenous (dietary) sources; the body cannot synthesise it. Remove the dietary source and plasma phytanic acid levels fall, the accumulation stops, and the nervous system is protected. This makes Refsum disease the most "treatable" hereditary neuropathy if diagnosed promptly.
The diagnostic tetrad
Peripheral neuropathy (typically motor > sensory, demyelinating or mixed) + retinitis pigmentosa (progressive visual loss from retinal degeneration, typically beginning with night blindness) + cerebellar ataxia + elevated CSF protein (without pleocytosis). Additional features: anosmia (loss of smell, often present from childhood and frequently overlooked), sensorineural deafness, ichthyosis (dry, scaly skin), cardiac arrhythmia (the most serious systemic complication). Any patient with the combination of retinitis pigmentosa + peripheral neuropathy should have plasma phytanic acid measured immediately.
Incidence
Very rare: estimated 1 in 1,000,000 – 1 in several million births. Because it is treatable, diagnosis is critically important. The condition is underdiagnosed globally, including in India, where the combination of RP + neuropathy is often managed as two separate conditions without the metabolic connection being made.
Appointment
040-44885000
Diagnosis at KIMS
Night Blindness, Stumbling, and the Diagnosis Made by a Blood Test
A 24-year-old man in Hyderabad has been struggling with his vision in dim light since his teenage years — progressive difficulty in darkness, requiring lights on throughout the house at night. In the past 2 years, his walking has become unsteady and he has noticed his feet feel numb and his shoes wear out unevenly. At 22, he was told by an ophthalmologist that he has retinitis pigmentosa (RP). He was referred to KIMS when his neurologist noted absent ankle reflexes alongside the RP.
At KIMS, the combination is immediately recognised: retinitis pigmentosa + peripheral neuropathy + unsteady gait (cerebellar component) + absent ankle reflexes. A specific question is asked: has he noticed any loss of his sense of smell? He has — since childhood, he had assumed it was normal. The diagnostic tetrad of Refsum disease is complete: RP + peripheral neuropathy + cerebellar ataxia + anosmia.
Plasma phytanic acid is measured. It is markedly elevated at 380 μmol/L (normal: less than 10 μmol/L). PHYH gene sequencing: compound heterozygous pathogenic mutations. Diagnosis: classic Refsum disease. ECG is performed: normal sinus rhythm (cardiac involvement is checked as it is potentially life-threatening).
The management plan at KIMS focuses immediately on diet. He is referred to a registered dietitian with metabolic disorder expertise for a comprehensive phytanic acid restriction protocol. The foods to eliminate: dairy products (butter, cream, cheese, full-fat milk — all contain phytanic acid from ruminant fat), lamb, beef, veal, mutton, and certain oily fish (tuna, cod). Foods to limit: white fish, other meats (lower phytanic acid than ruminant fat). At 6-month review: plasma phytanic acid has fallen to 45 μmol/L. His gait ataxia has improved. The neuropathy is stable. The retinitis pigmentosa cannot be reversed but its progression has slowed.
Book a Consultation
Speak directly with The KIMS Neuroscience team and the KIMS Refsum disease specialist team — neurology, metabolic medicine, ophthalmology, cardiology, clinical genetics, and metabolic dietetics coordinated under one roof. Family genetic workup arranged with priority. No referral required. Monday to Saturday.
040-44885000Acute crisis / arrhythmia: 040-44885000Clinical Features in Detail
The clinical profile of Refsum disease spans the eye involvement of retinitis pigmentosa, the demyelinating peripheral neuropathy with elevated CSF protein, cerebellar ataxia and the often-overlooked anosmia, the potentially fatal cardiac involvement, and the cutaneous / skeletal features that add additional diagnostic pointers.
Retinitis pigmentosa — the eye condition that signals Refsum
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterised by progressive degeneration of the photoreceptors (rods first, then cones). In Refsum disease, phytanic acid accumulates in the retinal pigment epithelium and disrupts photoreceptor metabolism. Night blindness (nyctalopia) is the first symptom, typically beginning in the second decade — difficulty seeing in dim light, requiring artificial light for tasks other people manage without. Visual field loss follows: concentric constriction of the visual field (tunnel vision), progressing to complete blindness in advanced cases. Ophthalmoscopy shows the characteristic bone spicule pigmentation of the mid-peripheral retina. The RP of Refsum disease is preventable from worsening and partially reversible with dietary treatment — unlike genetic RP from other causes.
Peripheral neuropathy — typically demyelinating
The peripheral neuropathy of Refsum disease is a progressive sensorimotor demyelinating neuropathy, with features overlapping Charcot-Marie-Tooth disease: distal weakness (foot drop, hand weakness), distal sensory loss, absent deep tendon reflexes. NCS shows reduced NCV (demyelinating pattern). CSF protein is markedly elevated (often 1–2 g/L, sometimes higher) without pleocytosis — a specific pattern called albumino-cytological dissociation, also seen in Guillain-Barré syndrome. The elevated CSF protein in a chronic neuropathy should prompt Refsum disease investigation.
Cerebellar ataxia and anosmia
Cerebellar involvement produces unsteadiness of gait (truncal ataxia), limb incoordination, and nystagmus in some patients. Anosmia (complete absence of sense of smell) is present in most Refsum disease patients from an early age, often so long-standing that it is not volunteered as a symptom — the patient has adapted to it. Specifically asking about smell at KIMS in any patient with RP + neuropathy reveals this important clue.
Cardiac involvement — the potentially fatal complication
Phytanic acid accumulates in the myocardium and cardiac conduction system, producing cardiomyopathy and cardiac arrhythmias. ECG abnormalities (prolonged QT, bundle branch block) can occur. In severe cases, life-threatening ventricular arrhythmias have been reported. At KIMS, baseline ECG and echocardiogram are performed in all Refsum disease patients. Annual cardiology review. Aggressive dietary treatment reduces cardiac phytanic acid accumulation and is important for cardiac protection.
Ichthyosis and skeletal abnormalities
Dry, scaly skin (ichthyosis) is present in many Refsum disease patients, resulting from phytanic acid disruption of normal lipid metabolism in the skin. Shortened fourth metatarsal and metacarpal bones, and epiphyseal dysplasia, are specific skeletal findings that, when seen on X-ray, provide an additional diagnostic pointer.
Diagnosis at KIMS — Plasma Phytanic Acid, Gene Sequencing & Multi-System Workup
Refsum disease diagnosis at KIMS combines fasting plasma phytanic acid (the diagnostic biochemical test), PHYH and PEX7 gene sequencing for definitive confirmation, NCS showing a demyelinating neuropathy, CSF with albumino-cytological dissociation, baseline ECG and echocardiogram for cardiac surveillance, and ophthalmological assessment for retinitis pigmentosa characterisation.
Plasma phytanic acid — the diagnostic test
Fasting plasma phytanic acid measured at KIMS through a metabolic reference laboratory. Normal: less than 10 μmol/L. Elevated in Refsum disease: typically >200 μmol/L in classic cases, sometimes higher. A single elevated plasma phytanic acid in the context of RP + neuropathy is diagnostic of Refsum disease pending genetic confirmation. Pristavanic acid (a phytanic acid precursor) is also measured.
PHYH and PEX7 gene sequencing
Confirms the specific mutations. PHYH mutations account for approximately 80–90% of Refsum disease; PEX7 mutations for the remainder. Both genes are included in the Refsum disease genetic panel at KIMS. The specific mutation confirms the diagnosis and enables carrier testing of parents and relatives.
NCS, CSF, ECG, and ophthalmology
NCS: demyelinating pattern, reduced NCV. CSF: elevated protein with normal cell count (albumino-cytological dissociation). ECG: baseline cardiac conduction assessment. Echocardiogram if ECG is abnormal. Ophthalmological assessment: visual field testing, ERG (electroretinogram), fundoscopy for RP characterisation.
Treatment
Treatment at KIMS — Diet, Plasma Exchange & Vitamin A
Refsum disease treatment at KIMS centres on the phytanic-acid-restricted diet — the primary, disease-halting intervention — supported by plasma exchange for acute phytanic acid crises and pre-operative metabolic optimisation, and modest vitamin A supplementation where appropriate to prevent dietary deficiency.
Phytanic acid-restricted diet, plasma exchange & vitamin A supplementation
Phytanic Acid-Restricted Diet — The Primary Treatment: Foods HIGH in phytanic acid to eliminate or severely restrict: all dairy products (butter, cream, cheese, full-fat milk, ghee, paneer) — the most significant dietary source in Indian cooking; lamb, mutton, beef, and veal (ruminant fat); certain oily fish (cod liver oil, tuna, swordfish). Foods LOWER in phytanic acid and acceptable in moderation: chicken, pork (non-ruminants contain much less phytanic acid); white fish (lower than oily fish); vegetables, fruits, legumes, rice (plant foods contain chlorophyll-derived phytol but in forms not readily absorbed). At KIMS, a registered dietitian experienced in metabolic disorders provides a personalised low-phytanic acid diet plan, Indian recipe substitutions, and monitoring of nutritional adequacy. Expected response: plasma phytanic acid levels fall gradually over weeks to months on a strict diet. Neurological symptoms — ataxia, neuropathy — stabilise and may partially improve. Retinitis pigmentosa: progression slows significantly; some visual field recovery has been reported in early-treated cases. The diet is lifelong and must not be relaxed even when well.
Plasma Exchange (Plasmapheresis) — For Acute Severe Manifestations: Plasmapheresis/lipid apheresis is reserved mainly for acute severe manifestations such as cardiac arrhythmias or extreme weakness. It is not a routine treatment for Refsum disease — dietary phytanic acid restriction is the cornerstone. Perioperative management should focus on avoiding fasting and catabolism; apheresis may be considered in selected high-risk situations. Acute rises in plasma phytanic acid can occur during illness, fasting, rapid weight loss (phytanic acid is stored in adipose tissue and released with fat catabolism), or dietary non-compliance. These acute rises can trigger rapid neurological deterioration, cardiac arrhythmia, or acute neuropathy worsening. Plasma exchange at KIMS rapidly lowers plasma phytanic acid levels by removing phytanic acid-containing plasma and replacing it with albumin or fresh frozen plasma. This is used for: acute phytanic acid crises; pre-operative preparation; and to rapidly lower very high levels before dietary restriction takes effect. Important instruction for Refsum disease patients: avoid prolonged fasting, crash diets, and any rapid weight loss — these mobilise phytanic acid from fat stores and cause acute deterioration.
Vitamin A supplementation: Vitamin A (retinol) supplementation has been used in some Refsum disease patients on the rationale that dietary restriction limits vitamin A intake from dairy and fish. However, the evidence for neurological benefit beyond phytanic acid restriction is limited, and high-dose vitamin A carries liver toxicity risk. At KIMS, modest vitamin A supplementation to prevent deficiency (not high-dose supplementation) is considered in patients on very strict dietary restriction.
Related Conditions
Refsum disease belongs to the family of hereditary polyneuropathies and leukodystrophies evaluated and managed at KIMS Neuroscience:
FAQs
Frequently Asked Questions
Night blindness and unsteady walking since the 20s. Neuropathy that no one has connected to the eye disease. The smell that has been gone so long the patient forgot it was ever there. A blood test that measures phytanic acid. A diet that, kept strictly, stops the disease from progressing.
Refsum disease is diagnosable and treatable at KIMS Neuroscience, Secunderabad, Hyderabad. Call 040-44885000 to book a Refsum disease assessment.
International enquiries: info@kimsneurosciences.com