Mucolipidosis type I (ML I) is an inherited lysosomal storage disease that results from a deficiency of the enzyme alpha-N -acetyl

neuraminidase Exo-α-sialidase (, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids: : Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycosidic linkag ...

(

sialidase Exo-α-sialidase (, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids: : Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycosidic link ...

). The lack of this

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

results in an abnormal accumulation of complex carbohydrates known as mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances accumulate in bodily tissues.

Presentation

Symptoms of ML I are either present at birth or develop within the first year of life. In many infants with ML I, excessive swelling throughout the body is noted at birth. These infants are often born with coarse facial features, such as a flat nasal bridge, puffy eyelids, enlargement of the gums, and excessive tongue size ( macroglossia). Many infants with ML I are also born with skeletal malformations such as hip dislocation. Infants often develop sudden involuntary muscle contractions (called myoclonus) and have red spots in their eyes ( cherry red spots). They are often unable to coordinate voluntary movement (called

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

). Tremors, impaired vision, and

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

also occur in children with ML I. Tests reveal abnormal enlargement of the liver (

hepatomegaly Hepatomegaly is enlargement of the liver. It is a non-specific sign (medicine), medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdomin ...

) and spleen (

splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulat ...

) and extreme abdominal swelling. Infants with ML I generally lack muscle tone (

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

) and have mental retardation that is either initially or progressively severe. Many patients suffer from failure to thrive and from recurrent

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gr ...

infections. Most infants with ML I die before the age of one year.

Related conditions

Other diseases that result from a deficiency in the sialidase enzyme are categorized in a broader group known as sialidoses. Because ML I is classified as a sialidosis, it is sometimes referred to as sialidosis type II. A rarer form of sialidosis – sialidosis type 1 – occurs in children and adolescents and is often referred to as the juvenile form of the disorder. Children usually begin to show symptoms during the second decade of life, and myoclonus and cherry-red macules are often the initial symptoms. Patients usually develop seizures and progressive deterioration of coordinated muscular and mental activities.

Pathophysiology

The role of

is to remove a particular form of sialic acid (a sugar molecule) from sugar-protein complexes (referred to as

glycoproteins Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

), which allows the cell to function properly. Because the enzyme is deficient, small chains containing the sugar-like material accumulate in

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

, bone marrow, and various cells that defend the body against

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

Diagnosis

The detection of high urinary sialyl oligosaccharides and the confirmation of lysosomal enzyme deficiency in leukocytes or cultured fibroblasts make the diagnosis.

Management

Treatment of sialidosis is similar to the other progressive myoclonic epilepsy disorders, which consists of managing seizures and myoclonus along with palliative, supportive, and rehabilitative care.

Notes

References

* - article derived from detail sheet available here

External links

* * {{Glycoproteinoses Glycoprotein metabolism disorders Skin conditions resulting from errors in metabolism Rare diseases