Mucolipidosis type I (ML I) is an inherited

lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

that results from a deficiency of the enzyme alpha-N -acetyl

neuraminidase Exo-α-sialidase (EC 3.2.1.18, 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)- glyc ...

(

sialidase Exo-α-sialidase (EC 3.2.1.18, 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)- glycos ...

). The lack of this

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

results in an abnormal accumulation of complex carbohydrates known as

mucopolysaccharides 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 o ...

, 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 An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

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 An eyelid is a thin fold of skin that covers and protects an eye. The levator palpebrae superioris muscle retracts the eyelid, exposing the cornea to the outside, giving vision. This can be either voluntarily or involuntarily. The human eye ...

, enlargement of the

gums The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health. Structure The gums are part of the soft tissue lin ...

, and excessive

tongue The tongue is a muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper surfa ...

size (macroglossia). Many infants with ML I are also born with skeletal malformations such as

hip In vertebrate anatomy, hip (or "coxa"Latin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) in medical terminology) refers to either an anatomical region or a joint. The hip region is ...

dislocation. Infants often develop sudden involuntary muscle contractions (called

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

) and have red spots in their eyes ( cherry red spots). They are often unable to coordinate voluntary movement (called

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

). Tremors, impaired vision, and

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

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

hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdo ...

) 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 circulatin ...

) and extreme

abdominal The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso ...

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 a potential manifestation of many different diseases a ...

) 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 gre ...

infections. Most infants with ML I die before the age of 1 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 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 as glycos ...

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

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

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

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

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