Mucopolysaccharidosis type I is a spectrum of diseases in the

mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosome, lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within ...

family. It results in the buildup of

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...

s (or GAGs, or mucopolysaccharides) due to a deficiency of alpha-L iduronidase, an enzyme responsible for the degradation of GAGs in lysosomes. Without this enzyme, a buildup of

dermatan sulfate Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. It is also referred to as chondroitin sulfate B, although it is no longer classifie ...

and heparan sulfate occurs in the body. MPS I may present with a wide spectrum of symptoms, depending on how much functional enzyme is produced. In severe forms, symptoms appear during childhood, and early death can occur due to organ damage. In mild cases, the patient may live into adulthood.

Signs and symptoms

MPS I affects multiple organ systems. Children with Hurler syndrome (severe MPS I) may appear normal at birth and develop symptoms over the first years of life. Developmental delay may become apparent by age 1–2 years, with a maximum functional age of 2–4 years. Progressive deterioration follows. One of the first abnormalities that may be detected is coarsening of the facial features; these symptoms can begin at 3–6 months of age. Skeletal abnormalities occur by about age 6 months, but may not be clinically obvious until 10–14 months. Patients may experience debilitating spine and hip deformities, carpal tunnel syndrome, and joint stiffness. Patients may be normal height in infancy, but stop growing by the age of 2 years. They may not reach a height of greater than 4 feet. Other early symptoms may include

inguinal In human anatomy, the inguinal region refers to either the groin or the lower lateral regions of the abdomen. It may also refer to: * Conjoint tendon, previously known as the inguinal aponeurotic falx, a structure formed from the transversus abdo ...

and

umbilical hernia An umbilical hernia is a health condition where the abdominal wall behind the navel is damaged. It may cause the navel to bulge outwards—the bulge consisting of abdominal fat from the greater omentum or occasionally parts of the small intestine. ...

s. Clouding of the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

and retinal degeneration may lead to blindness. The

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

and

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

may be enlarged due to the deposition of GAGs. Aortic valve disease may occur. Upper and lower respiratory-tract infections can be frequent. Most children develop limited language capabilities. Death usually occurs by age 10. In less severe cases, (Scheie syndrome, or attenuated MPS I), the presentation can vary considerably. Although symptoms generally begin to appear after age 5, the diagnosis is usually made after age 10. Intelligence may be normal, or mild learning disabilities may be present. As with the severe forms, visual problems may lead to blindness. Skeletal deformities and aortic valve disease may occur. These patients may live into adulthood.

Genetics

MPS I is inherited in an autosomal recessive manner. This means that patients with MPS I carry two defective copies of the ''IDUA'' gene on chromosome 4, with one defective copy being inherited from each parent. Persons born with one normal copy and one defective copy of the ''IDUA'' are called

carrier Carrier may refer to: Entertainment * ''Carrier'' (album), a 2013 album by The Dodos * ''Carrier'' (board game), a South Pacific World War II board game * ''Carrier'' (TV series), a ten-part documentary miniseries that aired on PBS in April 20 ...

s. They produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease.

Diagnosis

Classification

MPS I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme α-L-iduronidase. MPS I H, or Hurler syndrome, is the most severe of the MPS I subtypes. The other two types are MPS I S (

Scheie syndrome Scheie syndrome is a disease caused by a deficiency in the enzyme iduronidase, leading to the buildup of glycosaminoglycans (GAGs) in the body. It is the most mild subtype of mucopolysaccharidosis type I; the most severe subtype of this disease ...

) and MPS I H-S ( Hurler–Scheie syndrome). Because of the substantial overlap between Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome, some sources consider these terms to be outdated. Instead, MPS I may be divided into "severe", "intermediate", and "attenuated" forms.

Management

References

{{DEFAULTSORT:Mucopolysaccharidosis type I Proteoglycan metabolism disorders Autosomal recessive disorders Syndromes with intellectual disability Syndromes affecting hearing Skin conditions resulting from errors in metabolism