Zellweger spectrum disorders

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Zellweger spectrum disorders are a group of rare disorders that create the same disease process. [1] The subdivisions of this spectrum are hyperpipecolic acidemia, infantile Refsum disease, neonatal adrenoleukodystrophy, and Zellweger syndrome. It can also be referred to as peroxisomal biogenesis disorders, Zellweger syndrome spectrum, NALD, cerebrohepatorenal syndrome, and ZSS. [2] It can affect many body organs, including the kidneys, eyes, and hearing. [3] It is named after Hans Zellweger.

Contents

Signs and symptoms

The symptoms of the disorders can vary from every patient. Most symptoms are noticeable at birth. There is often lack in growth and muscle tone as the child develops. Also the disorders involve neurological problems. This would include frequent seizures, delays in intellectual development, and the absence in basic reflexes.[ citation needed ]

Facial abnormalities are also often common with patients. Including a small chin, upturned nostrils, and a mouth with a highly arched roof. There are also a variety of eye abnormalities that could happen. The eye abnormalities including clouding of the cataracts and retinopathy, which can lead to vision loss. Children with Zellweger Spectrum disorder can have hearing loss with onset during the first months following birth. [4]

Infants with the disorder can also have abnormalities including their organs. They might have a large spleen or liver, as well as heart defects. Including holes in the heart, and high blood pressure. Due to the lack of muscle tone, infants can face respiratory problems as the disease progresses.[ citation needed ]

Causes

Zellweger spectrum disorders are a group of autosomal recessive genetic disorders. They are caused due to pathogenic mutations in at least 13 different PEX genes that encode peroxins. [5] It affects the peroxisomes, which are organelles in the body that are meant to breakdown items like acids and toxic compounds. Both parents will have to have the recessive gene for the child to show symptoms. If one parent has the gene and the other one does not, the child will be a carrier and will not show symptoms. Any mutation involving the genes that create or work the peroxisomes can lead to the development of any of the Zellweger Spectrum Disorders. Both genders have an equal chance to end up with these disorders.[ citation needed ]

Diagnosis

Definite diagnosis requires evaluation of peroxisomal functions. [5] Mutation analysis is done from fibroblast cell lines. [6]

Treatment

Treatment may involve a team of specialists. This would include neurologists, endocrinologists, and pediatricians.[ citation needed ]

Early intervention is important when treating someone with these disorders. Special education, physical therapy, and other medical services to aid the child through treatment. There are medical trials taking place to learn more about these disorders. Most infants that are diagnosed do not live past 6 months. It can be diagnosed by a blood test looking for PEX genes in the body.[ clarification needed ] [7]

Epidemiology

It occurs in 1 in 50,000 individuals. [8]

Related Research Articles

<span class="mw-page-title-main">Adrenoleukodystrophy</span> Medical condition

Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by failure 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. The long chain fatty acid buildup causes damage to the myelin sheath of the neurons of the brain, resulting in seizures and hyperactivity. Other symptoms include problems in speaking, listening, and understanding verbal instructions.

<span class="mw-page-title-main">Macrocephaly</span> Abnormally large head size

Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to determine whether the syndrome is accompanied by particular disorders. Those with benign or familial macrocephaly are considered to have megalencephaly.

<span class="mw-page-title-main">Weissenbacher–Zweymüller syndrome</span> Medical condition

Weissenbacher–Zweymuller syndrome (WZS), also called Pierre-Robin syndrome with fetal chondrodysplasia, is an autosomal recessive congenital disorder, linked to mutations in the COL11A2 gene, which codes for the α2 strand of collagen type XI. It is a collagenopathy, types II and XI disorder. The condition was first characterized in 1964 by G. Weissenbacher and Ernst Zweymüller.

<span class="mw-page-title-main">Zellweger syndrome</span> Congenital disorder of nervous system

Zellweger syndrome is a rare congenital disorder characterized by the reduction or absence of functional peroxisomes in the cells of an individual. It is one of a family of disorders called Zellweger spectrum disorders which are leukodystrophies. Zellweger syndrome is named after Hans Zellweger (1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder.

<span class="mw-page-title-main">Blue diaper syndrome</span> Medical condition

Blue diaper syndrome is a rare, autosomal recessive or X linked recessive metabolic disorder characterized in infants by bluish urine-stained diapers. It is also known as Drummond's syndrome, and hypercalcemia.

Refsum disease is an autosomal recessive neurological disease that results in 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.

<span class="mw-page-title-main">Urofacial syndrome</span> Medical condition

Urofacial syndrome, or Ochoa syndrome, is an autosomal recessive congenital disorder characterized by an association of a lower urinary tract and bowel dysfunction with a typical facial expression: When attempting to smile, the patient seems to be crying or grimacing. It was first described by the Colombian physician Bernardo Ochoa in the early 1960s. The inverted facial expression presented by children with this syndrome allows for early detection of the syndrome, which is vital for establishing a better prognosis as urinary related problems associated with this disease can cause harm if left untreated. Incontinence is another easily detectable symptom of the syndrome that is due to detrusor-sphincter discoordination.

<span class="mw-page-title-main">Peroxisomal disorder</span> Medical condition

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.

<span class="mw-page-title-main">Fazio–Londe disease</span> Medical condition

Fazio–Londe disease (FLD), also called progressive bulbar palsy of childhood, is a very rare inherited motor neuron disease of children and young adults and is characterized by progressive paralysis of muscles innervated by cranial nerves. FLD, along with Brown–Vialetto–Van Laere syndrome (BVVL), are the two forms of infantile progressive bulbar palsy, a type of progressive bulbar palsy in children.

<span class="mw-page-title-main">Micrognathism</span> Condition in which the jaw is small

Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnormal tooth alignment and in severe cases can hamper feeding. It can also, both in adults and children, make intubation difficult, either during anesthesia or in emergency situations.

Rabson–Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance. The disorder is caused by mutations in the insulin receptor gene. Symptoms include growth abnormalities of the head, face and nails, along with the development of acanthosis nigricans. Treatment involves controlling blood glucose levels by using insulin and incorporating a strategically planned, controlled diet. Also, direct actions against other symptoms may be taken This syndrome usually affects children and has a prognosis of 1–2 years.

D-Bifunctional protein 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. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Infantile Refsum disease (IRD) 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.

<span class="mw-page-title-main">PEX5</span> Protein-coding gene in the species Homo sapiens

Peroxisomal targeting signal 1 receptor (PTS1R) is a protein that in humans is encoded by the PEX5 gene.

<span class="mw-page-title-main">PEX1</span> Protein-coding gene in the species Homo sapiens

Peroxisome biogenesis factor 1, also known as PEX1, is a protein which in humans is encoded by the PEX1 gene.

<span class="mw-page-title-main">ABCD3</span> Protein-coding gene in the species Homo sapiens

ATP-binding cassette sub-family D member 3 is a protein that in humans is encoded by the ABCD3 gene.

<span class="mw-page-title-main">Peroxisomal biogenesis factor 2</span> Protein found in humans

Peroxisomal biogenesis factor 2 is a protein that in humans is encoded by the PEX2 gene.

<span class="mw-page-title-main">PEX12</span> Protein-coding gene in humans

Peroxisome assembly protein 12 is a protein that in humans is encoded by the PEX12 gene.

<span class="mw-page-title-main">PEX6</span> Protein-coding gene in the species Homo sapiens

Peroxisome assembly factor 2 is a protein that in humans is encoded by the PEX6 gene. PEX6 is an AAA ATPase that localizes to the peroxisome. PEX6 forms a hexamer with PEX1 and is recruited to the membrane by PEX26.

<span class="mw-page-title-main">Heimler syndrome</span> Medical condition

Heimler syndrome is a rare autosomal recessive condition characterized by sensorineural hearing loss, amelogenesis imperfecta, nail abnormalities and occasional or late-onset retinal pigmentation

References

  1. ↑ "zellweger". Zellweger UK. Retrieved 20 February 2018.
  2. ↑ "Zellweger Spectrum Disorders". University of Michigan. Retrieved 20 February 2018.
  3. ↑ "Zellweger Spectrum Disorder". National Organization of Rare Diseases. Retrieved 20 February 2018.
  4. ↑ "Zellweger Syndrome". Hereditary Ocular Diseases. Retrieved 20 February 2018.
  5. 1 2 Berendse, Kevin; Engelen, Marc; Ferdinandusse, Sacha; Majoie, Charles B. L. M.; Waterham, Hans R.; Vaz, Frédéric M.; Koelman, Johannes H. T. M.; Barth, Peter G.; Wanders, Ronald J. A.; Poll-The, Bwee Tien (19 August 2015). "Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood". Journal of Inherited Metabolic Disease. 39 (1): 93–106. doi:10.1007/s10545-015-9880-2. PMC   4710674 . PMID   26287655.
  6. ↑ Ebberink, Merel S.; Mooijer, Petra A.W.; Gootjes, Jeannette; Koster, Janet; Wanders, Ronald J.A.; Waterham, Hans R. (January 2011). "Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder" (PDF). Human Mutation. 32 (1): 59–69. doi:10.1002/humu.21388. PMID   21031596. S2CID   24977902.
  7. ↑ "Zellweger Spectrum Disorder". Johns Hopkins Medicine. Retrieved 20 February 2018.
  8. ↑ "Zellweger Spectrum Disorders". U.S National Library of Medicine. Retrieved 20 February 2018.
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