Infantile Refsum Disease - Causes, Symptoms, and Treatment

Introduction

Infantile Refsum Disease (IRD) is a rare genetic disorder that comes under the peroxisomal biogenesis disorder, which is a large group of genetic disorders that affects the white matter of the brain and alters motor movements. Signs and symptoms usually start to appear during early infancy. This article will discuss infantile refsum disease, its symptoms, causes, diagnosis, and treatment in detail.

What Is Infantile Refsum Disease?

Infantile refsum disease is a rare medical condition that comes under the classification of Zellweger spectrum disorder. They are genetically inherited in an autosomal recessive pattern. Sometimes, symptoms might go unnoticed until early childhood. They are believed to be the least severe form of Zellweger spectrum disorders. However, in most cases, they are fatal. It is a neurological disorder affecting the brain and shows various other clinical manifestations such as visual and hearing impairment, liver involvement, seizures, dental abnormality, growth impairment, and orofacial abnormalities. Infantile refsum disease is a rare condition and is estimated to occur in around one in 50,000 population of North America.

What Are Zellweger Spectrum Disorders?

Zellweger spectrum disorders are a collective group of genetic disorders that occur due to the alteration or mutation of PEX genes. This disorder includes Zellweger syndrome (severe form) and neonatal adrenoleukodystrophy (intermediate form).

What Is the Cause of IRD?

Generally, a genetic disorder occurs when there is an abnormality or harmful changes to gene (DNA) material or due to wrong genetic material.

• Infantile refsum disease occurs when there is an alteration in the PEX gene responsible for the functioning of peroxisomes.

• Peroxisomes are sac-like structures that comprise enzymes essential for the breakdown of lipids (fat) and other toxic compounds that accumulate in the cells after a normal metabolic process.

• Mutations in the PEX gene can affect the functioning of peroxisomes.

• Peroxisomes fail to break down one of the other substances called phytanic acid, a chemical compound found in food substances.

• Consequently, phytanic acid accumulates excessively in the cells, damaging various organs such as the brain, eye, liver, kidney, and bones.

How Is IRD Inherited?

Infantile refsum disease is a genetically inherited condition acquired in an autosomal recessive pattern. The condition can be passed down through the family.

• Autosomal inheritance refers to the alteration or mutations in the first 22 non-sex chromosomes.

• Recessive inheritance refers to the condition that requires two copies of the altered gene to inherit the condition.

• The probability of inheriting the genetic condition to the child is 25 percent with each pregnancy, regardless of gender.

What Is the Difference Between Adult Refsum Disease And Infantile Refsum Disease?

Infantile refsum disease is seen in babies and young children, and they show symptoms such as poor feeding, floppy muscle tone, liver disease, seizures, and developmental delays. The infantile disease is more severe compared to adult refsum. Adult refsum is seen in late childhood or after and causes loss of smell, weakness, vision loss, numbness of hands and feet, and hearing impairment. Adult refsum does not affect the brain, so the individuals do not have seizures. Severe heart problems can develop later in life.

What Are the Signs and Symptoms?

The symptoms of infantile refsum disease usually begin during early infancy and progress over time. The condition primarily affects vision and motor skills but also involves other organs. Common symptoms of IRD include:

• Progressive loss of vision.

• Repetitive, involuntary movements of the eye (nystagmus).

• Decreased and weak muscle tone.

• Sensorineural hearing loss.

• Growth impairment.

• Mild dysmorphic facial features.

• An enlarged liver.

• Hepatic failure is noticed in children with jaundice.

• Progressive loss of muscle tone.

• Impairment of the retina (back wall of the eye) resulting in retinitis pigmentosa.

• Less active children develop osteoporosis (a bone disease with weak and brittle bone) and fractures.

• Adrenal insufficiency (a disorder affecting the adrenal gland resulting in insufficient hormone production) develops in later childhood.

• Kidney stones.

• Bone and skin changes.

• Leukodystrophy affects the central nervous system, causing loss of acquired skills, which may progress and be fatal.

How Is It Diagnosed?

Diagnosis of infantile refsum disease is primarily based on the patient's symptoms.

• The clinician diagnoses this condition through thorough history taking and detailed physical examination.

• The child’s family and medical history might be assessed.

• The clinician may evaluate the laboratory assessment through a blood test or urine sample to look for elevated levels of chemical compounds (phytanic acid) associated with IRD.

• Radiographic investigations such as MRI (magnetic resonance imaging) might be necessary to assess brain tissue and liver abnormalities.

• The clinician may refer the child and the parents for genetic testing to assess the abnormalities of the PEX gene that causes IRD.

• Biochemical tests are shown to be effective in diagnosing the condition.

How Is It Treated?

Since infantile refsum disease is a genetic disorder, currently, there is no cure for the condition. However, the affected child might be referred to the concerned specialists to address the symptoms. The affected child is given supportive and symptomatic care.

• The affected child may be referred to an ophthalmologist to treat the condition affecting the vision. The child requires surgery to remove the cataract from the eye immediately during early childhood.

• They are referred to an otolaryngologist to treat the hearing impairment. The affected child receives a hearing aid early to prevent deafness and mutism.

• They are advised to follow a strict diet to avoid foods rich in phytanic acids, such as beef, cow’s milk, dairy products, lamb, and rare seafood.

• Children with hepatic coagulopathy (a liver disorder due to impaired blood clotting and fibrinolytic systems, including deficiency of platelets and impairment) are treated with vitamin K supplementation.

• Children with liver function impairment are treated with primary bile acid therapy.

• Children with feeding difficulties are advised for feeding assistance.

• They may require a gastrostomy tube to maintain their calorie intake level.

• Patients with symptoms of seizure are advised to take standard epileptic medications.

• These children require lifelong monitoring and follow-up to maintain their vision, hearing, and liver function.

How Can Infantile Refsum Disease Be Prevented?

As of now, there are no proper measures to prevent this condition. However, parents with a familial history of infantile refsum disease are advised to receive genetic counseling to assess the risk of passing down the condition to their children while planning for a pregnancy.

Conclusion:

Infantile refsum disease is a rare genetically inherited condition that develops during infancy. They are caused by the mutations of the PEX gene affecting the functions of peroxisomes. The condition is characterized by excess accumulation of phytanic acid in the cells, impairing brain tissues and various organs. Even though IRD is a fatal disease, some patients have shown variable lifespans and survived their adulthood up to old age.