What is mucopolysaccharidosis?

This is the 4371th article of Da Yi Xiao Hu

Poor little dream

Xiao Meng (pseudonym) began to have unexplained spinal deformities at the age of 3. During the four years of treatment that followed, Xiao Meng's scoliosis not only did not improve, but gradually worsened. In addition, she also developed multiple deformities such as enlarged head, protruding forehead, enlarged chest, bulging abdomen, thick and short fingers, joint deformities, decreased vision and hearing. In December 2015, when Xiao Meng was already 7 years old, her disease was finally diagnosed as a rare mucopolysaccharidosis type I due to IDUA gene defect leading to α-L-iduronidase deficiency. However, up to now, there is no corresponding treatment drug for mucopolysaccharidosis in China, and foreign enzyme replacement drugs not only require lifelong medication, but are also quite expensive.

After many twists and turns, the parents learned that the Capital Institute of Pediatrics' Department of Hematology could treat children with mucopolysaccharidosis through bone marrow transplantation. They immediately rushed to Beijing and found the expert in this field, Director Shi, and expressed their concerns: it is difficult to find a bone marrow transplant donor, the cost is high, there are many complications, and the risk of death is high. Director Shi said that the matching before bone marrow transplantation is no longer like before, and parents who are half-matched with the child have become the preferred donors. The Capital Institute of Pediatrics' Department of Hematology's improved transplantation program has few side effects, postoperative rejection is controllable, and the cost of transplantation is relatively low.

On April 21, 2016, the team of the director of the department performed an allogeneic hematopoietic stem cell transplantation on Xiao Meng, which restored the enzyme that was close to 0 to the level of a normal person, and there were no obvious side effects and complications related to bone marrow transplantation. After staying in the laminar flow ward for more than a month, Xiao Meng was successfully discharged. After being discharged, Xiao Meng's rough face gradually became softer, and her figure became more slender and upright. It has been more than 10 months since Xiao Meng's transplantation, and all indicators have stabilized.

What is mucopolysaccharidosis?

Mucopolysaccharidosis is a group of diseases caused by congenital defects in lysosomal enzymes related to the degradation of various mucopolysaccharides, which prevent different mucopolysaccharides from being completely degraded and deposit in various tissue lysosomes and extracellular matrices, leading to functional damage of tissues and organs, and extensive accumulation in the heart, lungs, bones, joints, gastrointestinal system and central nervous system. This disease is a very important type of lysosomal storage disease, which can be divided into 7 types: I, II, III, IV, VI, VII, and IX. Among them, III is divided into four subtypes: IIIA, IIIB, IIIC, and IIID, and IV is divided into IVA and IVB subtypes. Although the pathogenic genes and clinical manifestations of each type are different, they are collectively referred to as mucopolysaccharidosis because the stored substrates are all mucopolysaccharides. Current studies have shown that the incidence of mucopolysaccharidosis in the population is about 1/4000000.

What are the symptoms of mucopolysaccharidosis?

Typical patients, taking type Ⅰ patients as an example:

1. Rough face

The head is large and boat-shaped, with a prominent forehead, thick eyebrows, puffy eyelids, protruding eyes, a low nose bridge, and upturned nostrils. The lips are large and thick; the tongue is large and tends to protrude out of the mouth. The gums are hyperplastic, and the teeth are small and widely spaced. The skin is thick and hairy, and the hair is very thick and coarse, with a low hairline.

2. Corneal opacity

As the disease progresses, corneal opacity becomes increasingly severe and may lead to blindness.

3. Joint stiffness

It affects large joints, such as shoulders, elbows, and knees, limiting their range of motion; while hand joints are affected, the characteristics of a "claw hand" may appear.

4. Short stature

The patient's neck becomes shorter, the spine becomes kyphotic, and growth almost stops at around 2 to 3 years old.

5. Enlarged liver and spleen

Abdominal distension and high abdominal pressure lead to umbilical hernia and inguinal hernia, which are prone to recurrence even after surgical repair.

6. Mental retardation

The patient may show intellectual disability at about 1 year old, with the best intelligence level being only 2 to 4 years old, indicating severe intellectual impairment.

7. Valvular heart disease

In most patients, cardiac involvement occurs in the late stages of the disease, manifesting as valvular disease, which can lead to congestive heart failure.

8. ENT lesions

There are often chronic recurrent rhinitis, rough breathing, snoring during sleep, chronic obstructive apnea, and coarse speech. Severe patients are often accompanied by chronic hearing loss.

The symptoms of patients with classic type II are usually milder than those of type I. This type mainly affects males, and the patients' corneas are not cloudy. Type III patients have intellectual disability as the main clinical manifestation. Type IV patients have loose wrist joints and protruding chests, similar to pigeon chests. Type VI patients have normal intelligence and obvious corneal opacity. The clinical manifestations of type VII patients can vary greatly, with severe manifestations such as fetal edema and mild patients may only have short stature.

How to prevent and treat mucopolysaccharidosis

So far, there is no good way to treat this disease. Symptomatic treatment is often used, but the effect is usually not ideal. Enzyme replacement and gene therapy are under study. The allogeneic hematopoietic stem cell transplantation mentioned in this article can significantly improve the prognosis of patients. After more than ten years of clinical practice in my country, the risk of this treatment method has been significantly reduced, and the cost is acceptable to most patients' families.

Families at high risk need prenatal diagnosis to prevent the disease from being born again in the same family.

This project is funded by Shanghai Science Education Development Foundation (Project No.: B202117)

Author: Shanghai Jing'an District Central Hospital

Dr. Xia Lemin