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In Paraíba, brothers thought they were dwarfs, but they have a rare genetic disease

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(Photo; reproduction/personal file)

Living in Princesa Isabel, Sertão da Paraíba, retired farmers Francisco, 70, and Judite Clementino, 66, took around 30 years to discover that 5 of the 16 children they had were born with a rare disease called mucopolysaccharidosis type IVA (MPS type IVA), which primarily compromises skeletal structure and growth.

One of the most visible signs is that the child stops growing, and this is what led Janailson Clementino, 33, one of the children with MPS type IVA, to believe he had it. of dwarfism. “All my life I’ve thought my brothers and I [que têm a doença] we were dwarfs. I used to joke that it was like the story of the 7 dwarfs, there were only 2 left to do”, he says in a good mood, who stopped growing at 5 years old and 1m tall.

In addition to Janailson, Josefa, 40; Cicero, 30; and Madalena, 28, and Damiana, who has since died, also have the disease, but they only discovered the disease in 2016, thanks to another of their sisters, Francinalva Clementino, 39, a community health worker, who participated in a conference on the disease.

“I had never heard of MPS, but listening to and seeing the pictures, I knew my brothers had it. At the end of the meeting, the organizers asked if we knew anyone, and I said yes,” says the agent.

According to Francinalva, the mother says that the brothers were born apparently healthy, but from the age of 5 some signs became clearer and others began to appear: they stopped growing, they had bone deformities in the back, legs and with clawed hands. .

From these changes, parents came to believe that their children had a disability, which was natural for them because they already had parents with some type of disability. At that time, comments the health worker, the parents had no education, and it was a difficult time.

“We didn’t go to a paediatrician, we only went to the health center when we were sick. They never wanted to know what my brothers had, they just took care of them,” he recalls.

Over the years, the condition of the brothers only worsened, with signs and symptoms ranging from body aches, respiratory and heart problems, fatigue, hearing loss, among others. Cícero and Madalena have lost mobility and strength in their lower limbs and use wheelchairs. Josefa manages to walk pushing the cart.

Janailson is in the best state of health. Although he has lost 25% of the hearing in his left ear, he walks, goes to parties with his friends and helps his mother with her siblings, feeding her or doing what she needs: “Thank God , I am a guy who never complained. about life. , I have always raised my head in the face of obstacles”.

Informing at the conference that his brothers had MPS, Francinalva received from the organizers the contact of a geneticist from Campina Grande, who took the case of the family. The diagnosis was confirmed by a specific genetic test, but the four brothers also underwent other tests and were evaluated by several specialists.

Doctor Paula Frassinetti V. de Medeiros, who takes care of the siblings, explains that MPS type IVA is an autosomal recessive disease, that is to say when both parents are healthy but carry a faulty gene.

In addition, the risk of children suffering from a recessive disease is higher when the parents are consanguineous. “Seu Francisco and Dona Judite are first cousins. And when it comes to a recessive disease, the couple had a high risk of 25% in each pregnancy of having a child with MPS IVA, which explains the fact that 5 of them have the disease”, comments the geneticist, who is a full member of the SBGM (Brazilian Society of Medical Genetics), professor of medical genetics at the UFCG (Federal University of Campina Grande) and responsible for enzyme replacement therapy (ER) of patients with MPS at the Alcides Carneiro University Hospital of the UFCG.

Francinalva says the family didn’t show much reaction to the discovery of the disease, but at first they resisted accepting treatment because of the distance: “My brothers had to go once a week from Princesa Isabel to Campina Grande [cerca de 290 km, mais de 4 horas de carro] taking the drugs to the hospital was too far and it was difficult for them. They thought about giving up, but when they got them to take the drugs in our town, they agreed.”

Despite the geneticist’s recommendation to start treatment as soon as possible — enzyme replacement therapy (ERT) involves replacing the enzyme from which the patient was born with a deficiency — the brothers did not have access to the drug until August 2021 , five years after diagnosis for some. problems ranging from requesting drugs at the public defender’s office to delaying distribution by the SUS (Sistema Único de Saúde).

With the help of Gláucia Barros, who is scientific advisor to Fedrann (Federation of Rare Disease Associations of the North and Northeast), who has a son with MPS, and Luana, who is from CER (Specialized Center in rehabilitation) from Princesa Isabel, the family received the drugs.

“Every Saturday, my brothers and I go to the hospital to take medicine, it’s like an IV. In general, we all had an improvement. He was very tired, his breathing was labored, his heartbeat accelerated. With the treatment, my fatigue has greatly decreased and my heart rate has stabilized. Madalena, who was the weakest, has the strength to hold the spoon, eat and brush her teeth on her own sometimes,” says Janailson.

Although she regrets not having discovered the disease earlier, Francinalva is delighted that the brothers are undergoing treatment: “They suffered a lot from the pain, today the quality of life has improved a lot”.

Learn more about the disease

1) What is MPS IVA, also known as Morquio A Syndrome? Mucopolysaccharidosis type IVA is part of a group of rare diseases of hereditary genetic origin, called mucopolysaccharidosis, also known as MPS.

MPS affects many organs and systems, but MPS type IVA primarily compromises skeletal structure and growth. As it is an autosomal recessive disease, that is to say that both parents are healthy, but carriers of a defective gene, the risk of having children with this syndrome is higher. when the parents are consanguineous (blood relationship).

2) What are the signs/symptoms?

The first signs are noticeable between 1 and 2 years old and are mainly related to the skeleton, such as bone deformities in the legs, spine and thorax, progressive slowing of growth, macrocrania (big head), short neck , joint hyperflexibility (very flexible joints), corneal opacity, recurrent respiratory infection and hearing loss.

Accumulation of a substance in the upper airways and tonsils predisposes to the development of obstructive sleep apnea due to obstruction of the upper airways. In the heart, heart valves are damaged by the deposition of this substance.

3) How is the diagnosis made?

The gold standard for diagnosis of MPS type IVA is enzymatic measurement performed in the blood with evidence of a decrease or absence of the enzyme N-acetylgalactosamine-6-sulfatase.

Genetic testing, with sequencing of the GALNS gene, is very useful for family genetic counseling. Often the radiologist can identify signs of mucopolysaccharidosis on x-rays of the skeleton, especially of the chest, spine, knees, and hands, but the type of MPS will only be determined by enzymatic or molecular evaluation.

Because it is a rare disease with multisystemic involvement, that is, it can affect all systems, it is common for the patient to consult several specialists for years until diagnosis is obtained. In general, the study of rare diseases is not part of medical training, and geneticists, who are the professionals best prepared for these diagnoses, are few in Brazil and located in large centers.

A late diagnosis can greatly affect the life of the patient, as the signs and symptoms will be evolved and the drugs that prevent the progression of the disease will not be as effective.

4) What are the main problems that the disease can cause to the patient?

It is important to emphasize that patients with MPS type IVA do not have intellectual disability. The main problems they present are skeletal deformities, which alter the act of walking, growing, breathing and can cause neurological problems in the spine. Additionally, patients with MPS type IVA may also have hearing loss and visual impairment.

5) What are the treatments?

Patients with MPS type IVA require multidisciplinary assistance, with speech therapists, physiotherapists, occupational therapists, nurses and with different medical specialties. Preferably, the treatment should be carried out in a reference center.

It should be emphasized that not all patients will experience the multiple manifestations of the disease, which tend to be more frequent and intense in those with the severe form of the disease.

Currently, enzyme replacement therapy, which involves replacing the enzyme with which the patient was born deficient, is administered once a week by intravenous infusion in the hospital. This is the most promising treatment, but it depends on when it was started, ideally shortly after birth.

6) Is the disease curable?

Type IVA MPS has no cure. The life expectancy of a patient with this disease is 30 years without treatment. With therapy, it is possible to increase the patient’s life expectancy and quality of life, but not to correct the sequelae of the disease.

8) Why does Paraíba have a high number of patients with the disease?

The frequency of VAT-type MPS varies from country to country and even within the same country. To get an idea of ​​the numbers, a study by the MPS Brasil Network published in 2021 showed that between 1982 and 2019, 1,652 patients were diagnosed with MPS in Brazil, however, MPS type IVA was the penultimate. less frequent, with 12.41%, mainly from Paraíba.

The high inbreeding in the state, resulting from Portuguese colonization, which had a strong tradition of marriage within the same family, contributes to the frequency of the disease in the state. This led to the emergence of a high number of patients with MPS type IVA in Paraíba due to the “founder effect”.

As already explained, consanguinity favors the occurrence of rare diseases with this type of recessive autosomal transmission, such as MPS type IVA. A couple who has a child with autosomal recessive transmission has a 25% chance of having another affected child with each pregnancy.

Another study on the ancestry and mutations of the GALN gene in patients with MPS type IVA, carried out at the University Hospital Alcides Carneiro, in partnership with the State University of Paraíba and the Federal University of Rio Grande do Sul, showed that most of the patients had the same mutation in the GALNS gene and the same common ancestry markers in the Iberian Peninsula, more precisely in Portugal. This study corroborates the historical data of the colonization of Paraíba.

The information comes from the UOL

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