Maroteaux-Lamy syndrome: Inherited lysosomal storage disorders

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. There are more than 60 lysosomal storage disorders. In MPS disorders patients, deficiency or malfunction of specific lysosomal enzymes results in an abnormal accumulation of certain complex carbohydrates known as mucopolysaccharides or glycosaminoglycans in the arteries, skeleton, eyes, joints, ears, skin, and teeth.

Mucopolysaccharidosis type VI is known by other names such as arylsulfatase-B Deficiency, MPS 6, MPS type VI, MPS VI, and poly-dystrophic dwarfism.

Signs and Symptoms

The symptoms, onset, and rate of progression of Maroteaux-Lamy syndrome vary greatly from one person to another. The disorder can be thought of as a spectrum or continuum of disease. Some of the commons symptoms are:

• Abnormality of the metaphysis

An abnormality of one or more metaphysis, i.e., of the somewhat wider portion of a long bone adjacent to the epiphyseal growth plate and growth during childhood.

• Chronic otitis media

Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.

• Coarse facial features

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

• Disproportionate short-trunk short stature

A type of disproportionate short stature identified by a short trunk but average-sized limbs.

• Epiphyseal dysplasia

Abnormal growth of the ends of long bones in arms and legs.

• Failure to thrive

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

• Joint stiffness

Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.

• Recurrent upper respiratory tract infections

Increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections.

• Sinusitis

Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.

Causes

Maroteaux-Lamy syndrome is caused by changes (mutations) in the ARSB gene. Genes provide instructions for making proteins that play an important role in many functions of the body. When a gene mutation happens, the protein product may be faulty, inefficient, or absent. And it depends upon the functions of the particular protein; this can affect many body organ systems.

Prevalence

According to the National Organization for Rare Disorders (NORD), The prevalence of all forms of MPS is estimated to be 1 in 65,000 births. Although the exact incidence and prevalence of the disorder are unknown, it is estimated to occur in one case in 250.000 to 600,000 individuals.

Diagnosis

A diagnosis of Maroteaux-Lamy syndrome is based upon identifying characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and numerous specialized tests.

In individuals suspected of Maroteaux-Lamy syndrome, the urine could be initially examined to assess glycosaminoglycans (GAGs) levels. Elevated levels of total urinary GAGs, with predominance of dermatan sulfate, suggests Maroteaux-Lamy syndrome. To confirm the diagnosis, healthcare professionals suggest a blood sample should be taken to measure the activity of the enzyme arylsulfatase B. Deficient or absent activity of this enzyme confirms the diagnosis of MPS 6.

Whenever possible, the sequencing of the ARSB gene should be performed to identify the causative mutations. Although not mandatory to confirm the diagnosis, identifying the mutations could help predict the clinical severity in the identification of carriers in the family and prenatal diagnosis in future at-risk pregnancies.

Treatments

The treatment of Maroteaux-Lamy syndrome is directed toward the specific signs and symptoms that are apparent in each patient. Treatment may need the coordinated efforts of a team of specialists. Pediatricians, surgeons, orthopedists, cardiologists, dental specialists, ear-nose-throat specialists (otorhinolaryngologists), specialists who deal with diseases of the lungs and respiratory tract (pulmonologists), specialists who assess and treat hearing problems (audiologists), specialists who assess and treat vision problems (ophthalmologists), and other healthcare professionals need to systematically and comprehensively plan the treatment. Genetic counseling may be of benefit to the affected person and their families.

The U.S. Food and Drug Administration (FDA) approved the drug Naglazyme (galsulfase) in 2005 for treating individuals with Maroteaux-Lamy syndrome.

There are other additional treatments, such as surgeries and physical therapies for treating MPS type 6.

Reference: https://rarediseases.org/rare-diseases/maroteaux-lamy-syndrome/

https://rarediseases.info.nih.gov/diseases/7095/mucopolysaccharidosis-type-vi