Also known as Morquio syndrome, it belongs to a group of inherited lysosomal storage disorders. Lysosomes are the digestive units in the cells and the enzymes within the lysosomes digest the nutrients. Among the individuals with this condition, the deficiency or the malfunction of various lysosomal enzymes can result in the accumulation of mucopolysaccharides in various parts of the body that can progressively continue to damage the tissues and different organ systems of the body. This mucopolysaccharide storage disease occurs in two forms; type IVA and IVB. The severe form is evident between the ages of one and three with the rapid progression. The slowly progressing form may not be evident until adolescence.
Causes
The genetic mutations identified for causing this condition are GALNS and GLB1 genes which produce enzymes that break down the large sugar molecules called glycosaminoglycans (GAGs). A genetic mutation in the gene GALNS results in the MPS IV type A and the mutation in the gene GLB1 causes the MPS IV type B. The genetic mutation reduces or completely eliminates the activity of their corresponding enzymes and as the result, the GAGs accumulate within cells, particularly inside the lysosomes. Hence, this can result in the development of the associated symptoms such as bone deformities. This condition is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. The parents of the affected individual each carry a single copy of the defective gene but don’t typically exhibit the symptoms associated with this condition.
Symptoms
The facial features include an enlarged head, prominent cheekbones, broad mouth, unusually small nose and subtle corneal clouding. They may also exhibit enlarged spleen and the liver. The children present growth retardation with the abnormally flexible joints that cause overall instability. Although the intelligence remains unimpaired, the high-frequency hearing problems are common. The front-to-back or side-to-side curvature of the spine, a prominent breastbone, hip dislocation, weakness of the legs and or additional abnormalities can also occur.
Diagnosis
The diagnosis is based on the medical history, skeletal X-rays and urine glycosaminoglycans analysis. The high quantity of keratan sulfate can also be detected in the urine sample. The confirmation of the diagnosis is possible by detecting the low GALNS enzyme activity or identifying the beta-galactosidase deficiency in the blood or skin cells. The genetic mutation responsible for the development of this condition can also help confirm the diagnosis.
Treatment
There is no cure for this disease. A recombinant human GALNS enzyme replacement therapy has been considered as the treatment option for this disorder. Other treatments can include surgery to fuse the bones of the upper neck to the base of the skull, surgical removal of the enlarged tonsils and adenoids to help with the upper-airway obstruction and the placement of prosthetic valve for ventricular hypertrophy. Some of the cases may require hearing aids and corneal replacement in the case of impaired vision.
References
https://rarediseases.org/rare-diseases/morquio-syndrome/
https://rarediseases.info.nih.gov/diseases/3785/mucopolysaccharidosis-type-iva
https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv#inheritance
