What Is I-Cell Disease?
I-Cell disease is a rare hereditary metabolic disorder that is debilitating and progressive in nature, affecting many body parts. Most individuals do not live past early childhood. Children suffering from I-cell disease at birth are small and have weak muscle tone (hypotonia) and a weak cry. The affected children gradually grow after birth and usually stop growing during or after the second year of life. There is delayed development, particularly of speech and fine motor skills such as sitting and standing.
Affected children have multiple bone abnormalities, many of which are present at birth. Affected children may have an abnormally rounded upper back, abnormally rotated clubfeet, abnormally shaped long bones, and small and short hands and fingers. People affected by this debilitating condition also suffer from severe joint deformities that significantly affect an individual's mobility. Most children with I-cell disease cannot walk independently. Multiple skeletal abnormalities are seen on X-rays in affected individuals.
Why Is It Called I-Cell Disease?
Leroy and DeMars first described the disease in 1967. Here, the lysosomes lack the necessary hydrolytic enzymes that are required to break down the cellular debris. So, this cellular debris is then accumulated within them and leads to the formation of the characteristic intracellular inclusions. These cells were therefore known as the inclusion cells or I-cells; hence, the disease was designated as I-cell disease. Spranger and Wiedermann then further classified this disease as mucolipidosis type II (ML II) because of its clinical characteristics, including mucopolysaccharidoses and sphingolipidoses.
What Are the Other Names of I-Cell Disease?
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I-cell disease.
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Inclusion cell disease.
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Mucolipidosis II.
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Mucolipidosis type II.
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Mucolipidosis II alpha or beta.
What Is the Frequency of I-Cell Disease?
I-cell disease or mucolipidosis II alpha or beta is a rare lysosomal storage disorder. The exact prevalence of the disease is unknown. It is estimated to occur in approximately one in 100,000 to 400,000 individuals all over the world.
What Are the Causes of I-Cell Disease?
Mutations in the GNPTAB (N-acetylglucosamine-1-phosphate transferase subunits alpha and beta) gene causes I-cell disease. This gene provides information for making two different subunits, alpha and beta, of an enzyme that is responsible for preparing certain newly synthesized enzymes for transport to lysosomes. Lysosomes are specialized cell organelles within the cell that use digestive enzymes to break down large biological molecules into smaller ones that can be utilized by the cells.
Mutations in the GNPTAB ((N-acetylglucosamine-1-phosphate transferase subunits alpha and beta) gene that cause I-cell disease prevents the production of any functional GlcNAc-1-phosphotransferase enzyme. Without the presence of this enzyme, digestive enzymes cannot be tagged and transported to lysosomes. The large molecules are accumulated within the lysosomes due to a lack of digestive enzymes. Disorders that cause large molecules to accumulate inside lysosomes are called lysosomal storage disorders. The signs and symptoms of I-cell disease are caused due to the lack of digestive enzymes within lysosomes and the effects that occur due to the absence of these enzymes outside the cell.
What Is the Mode of Inheritance of I-Cell Disease?
The disease is inherited as an autosomal recessive hereditary disorder, meaning both copies of the gene in each cell are mutated. The parents of an affected individual each carry one copy of the mutated gene, but they do not exhibit signs and symptoms of the condition in particular.
What Are the Signs and Symptoms of I-Cell Disease?
Some of the morphological features associated with I-cell disease are present since birth (congenital), whereas other clinical features may appear between six to ten months of age. Craniofacial abnormalities include distinct facial features with a depressed nasal bone, a long and narrow head, an abnormally high forehead, cloudy corneas, and skin folds on the inner corners of the eyes. The skin is unusually thick and tight in certain body parts like the face, arms, and legs.
Skeletal malformations may be evident in the affected children, including abnormal spine curvature from side to side (scoliosis) and abnormal spine curvature from front to back (kyphosis), a very short neck, congenital hip dislocations, enlargement of the top portion of the spine (lumbar gibbus), and restricted shoulder mobility. Skeletal abnormalities may also include vertebral breaking and wedging, wider spacing between the ribs, and unusual positioning of the fingers. Sometimes, infants with I-cell disease may have fused fingers (split hand deformity). There is a severe delay in developing gross and fine motor skills, poor speech development, hearing loss, weak muscle tone (hypotonia), and mental retardation. Growth retardation usually results in short stature (dwarfism). In some children, a portion of the intestines out pouch through the belly button (umbilical hernia) or the groin (inguinal hernia). Abnormal liver enlargement (hepatomegaly) is often observed in infants with I-cell disease.
Additional symptoms of I-cell disease include frequent respiratory infections, constipation or diarrhea, gingival enlargement, and limited joint movement that is frozen in place (contractures). A few children with I-cell disease may also have heart valve defects, cardiomegaly, congestive heart failure, and heart murmurs. Affected children with I-cell disease usually die in early childhood, although a few patients live up to their teens.
What Is the Diagnosis of I-Cell Disease?
The disease can be diagnosed prenatally (before birth) using amniocentesis or chorionic villus sampling. Amniocentesis is a scientific procedure in which a small sample of the amniotic fluid surrounding the fetus is removed, and cells from the fluid are sent to the laboratory for testing. Chorionic villus sampling (CVS) is a prenatal diagnostic procedure in which a small piece of tissue is removed from the placenta. The I-cell disease is diagnosed if abnormally low levels of the enzyme UDP-N-acetyl glucosamine-1-phosphotransferase are detected in amniotic fluid cells or chorionic villi of the placenta.
An infant's confirmed diagnosis of I-cell disease is established by a complete clinical evaluation, patient medical history, and specialized diagnostic laboratory testing. Lysosomal enzymes are particularly increased in the blood serum and markedly reduced in cultured fibroblasts.
What Is the Treatment of I-Cell Disease?
The line of treatment for I-cell disease is symptomatic. Antibiotics are prescribed for treating respiratory infections. Yearly flu shots are extremely important. Physical exercises should be performed to maintain joint function and mobility. Total hip replacement surgery is found to be effective when performed after puberty. Hearing aids are useful in case of hearing loss. Heart problems may be treated surgically in certain cases. Genetic counseling is advisable for families having children with this disorder.
Conclusion
I-cell disease is an extremely rare inherited metabolic lysosomal storage disorder. If not treated, it may result in the early death of the affected individual. It is a debilitating type of disorder. More research is aimed at experimental therapies that can treat I-cell disease as early as possible.
