Zellweger syndrome is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD). The other two disorders are neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). Although all have a similar molecular basis for disease, Zellweger syndrome is the most severe of these three disorders.

Zellweger syndrome is associated with impaired neuronal migration, neuronal positioning, and brain development. In addition, individuals with Zellweger syndrome can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as hypomyelination. Myelin is critical for normal CNS functions, and in this regard, serves to insulate nerve fibers in the brain. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.

Zellweger syndrome can also affect the function of many other organ systems. Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts. Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat.

Infantile Refsum disease is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD). The other two disorders are Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD). Although they share a similar molecular basis for disease, Infantile Refsum disease is less severe than Zellweger syndrome.

Infantile Refsum disease is a developmental brain disorder. In addition, patients can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as (hypomyelination). Myelin is critical for normal CNS functions. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.

Infantile Refsum disease can also affect the function of many other organ systems. Patients can show craniofacial abnormalities, hepatomegaly (enlarged liver), and progressive adrenal dysfunction. Newborns may present with profound hypotonia (low muscle tone), and a poor ability to feed. In some patients, a progressive leukodystrophy has been observed that has a variable age of onset.

Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation or remission occur. Symptoms also include ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including retinitis pigmentosa, cataracts, and night blindness. In 80% of patients diagnosed with Refsum disease, sensorineural hearing loss has been reported. This is hearing loss as the result of damage to the inner ear or the nerve connected to ear to the brain.

Infantile Refsum disease (IRD), also called infantile phytanic acid storage disease, is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the Zellweger spectrum. These are disorders of the peroxisomes that are clinically similar to Zellweger syndrome and associated with mutations in the "PEX" family of genes. IRD is associated with deficient phytanic acid catabolism, as is Adult Refsum disease, but they are different disorders that should not be confused.

Peroxisomal disorders represent a class of medical conditions caused by defects in peroxisome functions. This may be due to defects in single enzymes important for peroxisome function or in peroxins, proteins encoded by "PEX" genes that are critical for normal peroxisome assembly and biogenesis.

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease, is an autosomal recessive neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991). Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. Humans obtain the necessary phytanic acid primarily through diet. It is still unclear what function phytanic acid plays physiologically in humans, but has been found to regulate fatty acid metabolism in the liver of mice.

Neonatal adrenoleukodystrophy is an inborn error of peroxisome biogenesis. It is part of the Zellweger spectrum. It has been linked with multiple genes (at least five) associated with peroxisome biogenesis, and has an autosomal recessive pattern of inheritance.

Peroxisome biogenesis disorders (PBDs) include the Zellweger syndrome spectrum (PBD-ZSD) and rhizomelic chondrodysplasia punctata type 1 (RCDP1). PBD-ZSD represents a continuum of disorders including infantile Refsum disease, neonatal adrenoleukodystrophy, and Zellweger syndrome. Collectively, PBDs are autosomal recessive developmental brain disorders that also result in skeletal and craniofacial dysmorphism, liver dysfunction, progressive sensorineural hearing loss, and retinopathy.

PBD-ZSD is most commonly caused by mutations in the "PEX1", "PEX6", "PEX10", "PEX12", and "PEX26" genes. This results in the over-accumulation of very long chain fatty acids and branched chain fatty acids, such as phytanic acid. In addition, PBD-ZSD patients show deficient levels of plasmalogens, ether-phospholipids necessary for normal brain and lung function.

RCDP1 is caused by mutations in the "PEX7" gene, which encodes the PTS2 receptor. RCDP1 patients can develop large tissue stores of branched chain fatty acids, such as phytanic acid, and show reduced levels of plasmalogens.

The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency.

Some common symptoms in Malonyl-CoA decarboxylase deficiency, such as cardiomyopathy and metabolic acidosis, are triggered by the high concentrations of Malonyl-CoA in the cytoplasm. High level of Malonyl-CoA will inhibits β-oxidation of fatty acids through deactivating the carrier of fatty acyl group, CPT1, and thus, blocking fatty acids from going into the mitochondrial matrix for oxidation.

A research conducted in Netherlands has suggested that carnitine supplements and a low fat diet may help to reduce the level of malonic acid in our body.

Some specific symptoms vary from one type of leukodystrophy to the next but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head. Botox therapy is often used to treat patients with spasticity. Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation. Epilepsy is commonplace for patients of all ages. More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile x-linked adrenoleukodystrophy is shown in the 1992 film, "Lorenzo's Oil".

Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death. While treatments do exist, most are in the experimental phase and can only promise a halt in the progression of symptoms, although some gene therapies have shown some symptomatic improvement. The debilitating course of the disease has led to numerous philosophical and ethical arguments over experimental clinical trials, patients’ rights and physician-assisted suicide.

In addition to genetic tests involving the sequencing of "PEX" genes, biochemical tests have proven highly effective for the diagnosis of Zellweger syndrome and other peroxisomal disorders. Typically, Zellweger syndrome patients show elevated very long chain fatty acids in their blood plasma. Cultured primarily skin fibroblasts obtained from patients show elevated very long chain fatty acids, impaired very long chain fatty acid beta-oxidation, phytanic acid alpha-oxidation, pristanic acid alpha-oxidation, and plasmalogen biosynthesis.

Symptoms include poor growth, loss of muscle coordination, muscle weakness, visual problems, hearing problems, learning disabilities, heart disease, liver disease, kidney disease, gastrointestinal disorders, respiratory disorders, neurological problems, autonomic dysfunction and dementia. Acquired conditions in which mitochondrial dysfunction has been involved are: diabetes, Huntington's disease, cancer, Alzheimer's disease, Parkinson's disease, bipolar disorder, schizophrenia, aging and senescence, anxiety disorders, cardiovascular disease, sarcopenia, chronic fatigue syndrome.

The body, and each mutation, is modulated by other genome variants; the mutation that in one individual may cause liver disease might in another person cause a brain disorder. The severity of the specific defect may also be great or small. Some minor defects cause only "exercise intolerance", with no serious illness or disability. Defects often affect the operation of the mitochondria and multiple tissues more severely, leading to multi-system diseases.

As a rule, mitochondrial diseases are worse when the defective mitochondria are present in the muscles, cerebrum, or nerves, because these cells use more energy than most other cells in the body.

Although mitochondrial diseases vary greatly in presentation from person to person, several major clinical categories of these conditions have been defined, based on the most common phenotypic features, symptoms, and signs associated with the particular mutations that tend to cause them.

An outstanding question and area of research is whether ATP depletion or reactive oxygen species are in fact responsible for the observed phenotypic consequences.

Cerebellar atrophy or hypoplasia has sometimes been reported to be associated.

Malonyl-CoA decarboxylase deficiency (MCD), or Malonic aciduria is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-Coa decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into Acetyl-CoA and carbon dioxide.

ALD can present in different ways. The different presentations are complicated by the pattern of X-linked recessive inheritance. There have been seven phenotypes described in males with "ABCD1" mutations and five in females. Initial symptoms in boys affected with the childhood cerebral form of ALD include emotional instability, hyperactivity and disruptive behavior at school. Older patients affected with the cerebral form will present with similar symptoms. Untreated, cerebral ALD is characterized by progressive demyelination leading to a vegetative state and death. Adult males with an adrenomyeloneuropathy presentation typically present initially with muscle stiffness, paraparesis and sexual dysfunction. All patients with clinically recognized ALD phenotypes are at risk for adrenal insufficiency. There is no reliable way to predict which form of the disease an affected individual will develop, with multiple phenotypes being demonstrated within families. Onset of adrenal insufficiency is often the first symptom, appearing as early as two years of age.

Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria, the organelles that generate energy for the cell. Mitochondria are found in every cell of the human body except red blood cells, and convert the energy of food molecules into the ATP that powers most cell functions.

Mitochondrial diseases are sometimes (about 15% of the time) caused by mutations in the mitochondrial DNA that affect mitochondrial function. Other mitochondrial diseases are caused by mutations in genes of the nuclear DNA, whose gene products are imported into the mitochondria (mitochondrial proteins) as well as acquired mitochondrial conditions. Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. The subclass of these diseases that have neuromuscular disease symptoms are often called a mitochondrial myopathy.

Pipecolic acidemia, also called hyperpipecolic acidemia or hyperpipecolatemia, is a very rare autosomal recessive metabolic disorder that is caused by a peroxisomal defect.

Pipecolic acidemia can also be an associated component of Refsum disease with increased pipecolic acidemia (RDPA), as well as other peroxisomal disorders, including both infantile and adult Refsum disease, and Zellweger syndrome.

The disorder is characterized by an increase in pipecolic acid levels in the blood, leading to neuropathy and hepatomegaly.

Leukodystrophy is one of a group of disorders characterized by degeneration of the white matter in the brain. The word "leukodystrophy" comes from the Greek roots "leuko", "white", "dys", "abnormal", and "troph", "growth". The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers.

When damage occurs to white matter, immune responses can lead to inflammation in the CNS, along with loss of myelin. The degeneration of white matter can be seen in a MRI and used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms including decreased motor function, muscle rigidity, and eventually degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor as infants are given a lifespan of 2–8 years (sometimes longer), while adults typically live more than a decade after onset. There is a great lack of treatment, although cord blood and hematopoietic stem cell transplantation (bone marrow transplant) seem to help in certain types while further research is being done.

The combined incidence of the leukodystrophies is estimated at 1:7,600. The majority of types involve the inheritance of a recessive, dominant, or X-linked trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.

Adrenoleukodystrophy is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by the relevant enzymes not functioning properly, which then causes damage to the myelin sheath of the nerves, resulting in seizures and hyperactivity. Other side effects include problems with speaking, listening, and understanding verbal instructions.

In more detail, it is a disorder of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes. Clinically, ALD is a heterogeneous disorder, presenting with several distinct phenotypes, and no clear pattern of genotype-phenotype correlation. As an X-linked disorder, ALD presents most commonly in males, however approximately 50% of heterozygote females show some symptoms later in life. Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in terms of onset and clinical severity, ranging from adrenal insufficiency to progressive paraparesis in early adulthood (this form of the disease is typically known as adrenomyeloneuropathy).

ALD is caused by mutations in "ABCD1", a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The exact mechanism of the pathogenesis of the various forms of ALD is not known. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid (26:0). The level of cerotic acid in plasma does not correlate with clinical presentation. Treatment options for ALD are limited. Dietary treatment is with Lorenzo's oil. For the childhood cerebral form, stem cell transplant and gene therapy are options if the disease is detected early in the clinical course. Adrenal insufficiency in ALD patients can be successfully treated. ALD is the most common peroxisomal inborn error of metabolism, with an incidence estimated between 1:18,000 and 1:50,000. It does not have a significantly higher incidence in any specific ethnic groups.

Occurrence of acatalasia is often the result of mutation in the CAT gene which codes for the enzyme catalase.

OA1 is recognized by many different symptoms. Reduced visual acuity is accompanied by involuntary movements of the eye termed as nystagmus. Astigmatism is a condition wherein there occurs significant refractive error. Moreover, ocular albino eyes become crossed, a condition called as ‘lazy eyes’ or strabismus. Since very little pigment is present the iris becomes translucent and reflects light back. It appears green to blueish red. However, the most important part of the eye, the fovea which is responsible for acute vision, does not develop properly, probably indicating the role of melanin in the development stages of the eye. Some affected individuals may also develop photophobia/photodysphoria. All these symptoms are due to lack of pigmentation of the retina. Moreover, in an ocular albino eye, nerves from back of the eye to the brain may not follow the usual pattern of routing. In an ocular albino eye, more nerves cross from back of the eye to the opposite side of the brain instead of going to the both sides of the brain as in a normal eye. An ocular albino eye appears blueish pink in color with no pigmentation at all unlike a normal eye. Carrier women have regions of hypo- and hyper-pigmentation due to X-inactivation and partial iris transillumination and do not show any other symptoms exhibited by those affected by OA1.

Acatalasia (also called acatalasemia, or Takahara's disease) is an autosomal recessive peroxisomal disorder caused by low levels of the enzyme catalase.

Ocular albinism type 1 (OA1), also called Nettleship–Falls syndrome, is the most common type of ocular albinism, with a prevalence rate of 1:50,000. It is an inheritable classical Mendelian type X-linked recessive disorder wherein the retinal pigment epithelium lacks pigment while hair and skin appear normal. Since it is usually an X-linked disorder, it occurs mostly in males, while females are carriers unless they are homozygous. About 60 missense and nonsense mutations, insertions, and deletions have been identified in "Oa1". Mutations in OA1 have been linked to defective glycosylation and thus improper intracellular transportation.

The eponyms of the name "Nettleship–Falls syndrome" are the ophthalmologists Edward Nettleship and Harold Francis Falls.

In contrast to Hartnup disease and related tubular conditions, Fanconi syndrome affects the transport of many different substances, so is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules.

Different diseases underlie Fanconi syndrome; they can be inherited, congenital, or acquired.

DBP deficiency can be divided into three types:

- type I, characterized by a deficiency in both the hydratase and dehydrogenase units of D-BP

- type II, in which only the hydratase unit is non-functional

- type III, with only a deficiency in the dehydrogenase unit

Type I deficient patients showed a large structural modification to the D-BP as a whole. Most of these individuals showed either a deletion or an insertion resulting in a frameshift mutation. Type II and III patients showed small scale changes in the overall structure of D-BP[6]. Amino acid changes in the catalytic domains or those in contact with substrate or cofactors were the main cause of these variations of D-BP deficiency. Other amino acid changes were seen to alter the dimerization of the protein, leading to improper folding. Many mutations have been found in the gene coding for D-BP(HSD17B4)on the q arm two of chromosome five (5q2) in "Homo sapiens", most notably individuals homozygous for a missense mutation (616S).