Mucopolysaccharidoses (MPS II, Hunter syndrome)

Palquiran, Paul Christian T.

Pama, Joao Artemio Lorenzo P.
Parreño, Diana Rose D.
Payba, Jason Albert S.
Pelayo, Gian Ignatius E.
Pendon, Kim Janelle M.
Perez, Danica G.
Pido, Theo Joseph D.
Quidato, Jun Pretzel E.
Quijano, Jorian Floyd M.
Rabanes, Ann Christine Grace C.
 1. Planning/Preparation (Gian, Theo, Pretzel) *done na kami di but let us know lang if may pa-
change hehe thank you*
- prepare self and medical data
- rapport & goals/agenda
- concerns, expectations, perceptions (what is their experience like?)
- current knowledge/understanding
- identify family resources, beliefs, and values

Input Here:

Genetic counseling aims to provide explanations to both patient and family about a particular genetic
condition. With the diagnosis of a genetic condition – Mucopolysaccharidosis type II (Hunter Disease),
advance preparation of knowledge ranging from the disease’s etiology to its management and the
preparation of the patient’s medical data are crucial pre-counseling practices that must be observed.
On counseling day, rapport must be properly established, and information must be presented in a
neutral and non-directive manner in order to avoid possible barriers in communication.

It is imperative to determine first the parents’ current understanding of their child’s diagnosis in order to
correct misconceptions, to clarify topics that are not yet fully understood, and to touch on important
information not yet known to the patient’s family. By doing this, the counselor could save time and make
sure that everything is covered. The parents or caregivers of these patients would often come in with
many questions posed, and as the doctor-counselor, one must be able to attend and provide the
answers that they seek.

We have to educate them regarding the pattern of inheritance, the risks of other family members and
the patient’s eventual offspring to develop the disease, and the natural course of the patient in terms of
prognosis and developing complications. Establishing the tests for diagnosis, the appropriate
management options, alternatives, and the need for admission or referral must also be highlighted
during the consultation to allow the family to choose the best plan of action for the patient.

Moreover, the counselor has to explore the family’s resources, beliefs, and values to further tailor the
session to what they need and to offer more options based on their background. Ultimately, the
counselor must see to it that decisions made along the way are always provided with support to allow
family coping.

2. The Body (Diana, Kim, Jorian)

- The disease (MPS II: Hunter syndrome) explain in layman
- epidemiology, etiology, genetic aspect (chance of recurrence)
- features, natural history, prognosis
- test & management options for patient and family

Input Here:

Knowledge about Hunter Syndrome or MP-II should be communicated in a manner that the family can
understand, preferably in layman’s terms. Mucopolysaccharidosis is a progressive hereditary disease
which is caused by mutations of genes that code for enzymes responsible for breaking down
glycosaminoglycans.
Glycosaminoglycans (GAGs) have important roles in our body such as contributing to properties of
connective tissues and cell membranes, but they must be regulated by synthesis and degradation to
maintain a constant amount within the body.

It is a progressive disease in that over time, if these substances are not broken down, they can build up
in cells which can produce specific abnormalities in different parts of the body.
In Hunter Syndrome, a type of MPS, there is a deficiency of an enzyme that degrades GAGs called I2S
or iduronate 2-sulfatase which is caused by mutations of the gene IDS.

The family should also know about the genetic aspects of the disease and its chances of recurrence.
Hunter Syndrome is an X-linked recessive disorder with an incidence of 0.3–0.71 per 100,000 live
births. Since it is inherited in an X-linked manner, it manifests almost exclusively to males.

 Males have only one X chromosome so one altered copy of the gene in each cell is enough to
cause the disease.
 In females, having two X chromosomes, a mutation has to occur in both copies of the gene to
cause the disease, but this is unlikely.
 A carrier mother will have a 50% chance of passing the mutated gene to her sons and
daughters, while a father with the disease will pass the mutated gene to all of his daughters
and none to his sons.

Usually, the disease presentation of Hunter Syndrome or MP-II presents at around 2-4 years of age. It
initially presents as hydrocephalus which appears as macrocephaly or a “big head”, and eventually,
behavior symptoms such as attention difficulties, hyperactivity and intellectual disability arise. Hunter
syndrome has a wide clinical spectrum that involves multiple organs, which presents as having a
coarse facial feature, short stature, dysostosis multiplex or in simple words, a constellation of
radiographic abnormalities such as limb deformity, hepato- and splenomegaly.

The prognosis for Hunter Syndrome depends on the form of the disease.

 Those with

There are different tests used to diagnose Hunter Syndrome.

 First, these individuals are screened by measuring their urinary and plasma GAG levels. Infants
with mucopolysaccharide syndrome have elevated GAG levels.
 Skeletal survey is also performed on patients with clinical features of Hunter syndrome. Some
of the features seen are J shaped deformity in sella turcica, oar shaped ribs with scoliosis and
kyphosis of the vertebral column.
 Individuals suspected of MPS disorder based on its clinical features, imaging, or urinary GAG
screening tests need to undergo enzyme assay.
 Serum, leukocytes, or cultured fibroblasts are needed to measure lysosomal enzymes,
specifically the I2S enzyme activity.

Deficiency of this enzyme is the definitive diagnosis of the disease. This test could be done by
uncultured chorionic villi sampling at 11 weeks or amniocentesis at 16 weeks.

The family should also know about the different treatment options available. Two of the approved
treatments are: (1) Enzyme replacement therapy (ERT) done to normalize IDS level enzymes in the
body. This would improve somatic symptoms such as coarse facial features, joint contractures, and
joint mobility. However, it cannot cross the BBB so it proves to have no effect on CNS symptoms. and

(2) Hematopoietic stem cell transplantation (HSCT) which is more cost-effective as it would only be
done once. This also shows significant improvement on somatic symptoms such as
 hepatosplenomegaly, joint stiffness, and facial appearance, skin changes, obstructive sleep apnea,
heart disease, communicating hydrocephalus, and hearing loss. It also helps in normalizing enzyme
activity in serum and urinary GAG excretion.

First, ERT is done by administering recombinant IDS once weekly via IV route. This is

HSCT

Patient education regarding long-term monitoring is also important.

 Regular follow-ups to cardiologists and orthopedic surgeons are needed due to the progressive
nature of the disease.
 Symptomatic therapy could be done when problems do arise.
 Also, the cognitive learning and psychological status of the child should be monitored since
most patients with hunter syndrome had increased risk of suffering from depression and social
withdrawal.

CCC. Giugliani, Roberto et al. “Guidelines for diagnosis and treatment of Hunter Syndrome for
clinicians in Latin America.” Genetics and molecular biology vol. 37,2 (2014): 315-29.
doi:10.1590/s1415-47572014000300003

AAA. Hashmi MS, Gupta V. Mucopolysaccharidosis Type II. [Updated 2021 Aug 1]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK560829/

3. Summary and closing (Jason, Tine, Paul)

- goals of the family + plan (facilitate decision making)
- other education parts: how to raise the child, what to expect, possible economic, psychological and
social impact
- Offer available resources: support group, referral & follow up
- end with a good note showing hope and support
Input Here:
It is important to reemphasize the important details from the discussion, to provide them with
informative materials (e.g. websites, support groups’ written materials), and to complete necessary
paperwork before ending the session.

The family should be made aware of the possible outcomes of the disease as well. A study in the
Philippines [DDD]showed that a majority of Filipino children with Hunter syndrome manifested with
structural, ophthalmologic, otorhinologic, respiratory, cardiac, abdominal and neurological signs and
symptoms.
It is important to note that the severe phenotype of MPS II is more prevalent than the attenuated
phenotype[GGG]. This poses a significant burden on the average Filipino family and counseling is
important for the patient to thrive.

A history of Hunter syndrome in the family should alert the family and inform their physician so an
increased suspicion for the disorder may be warranted. Early diagnosis of the disease is paramount for
the course of the patient, and the family’s, life.

Upon diagnosis, the family should be prepared for the previously stated manifestations of the disease
and should treat the patient with care. Neurological manifestations are common in these patients and
the family must devote time and effort in helping the child with daily life.

As the physician, a comprehensive disability assessment on activities of daily living should be done to
determine the baseline and future deterioration of the patient. This assessment will help define the
multidisciplinary approach that must be used.

Fortunately, Republic Act 10747, or the Rare Diseases Act of the Philippines, was passed last 2015
which allocates a budget with fiscal benefits for the treatment of rare diseases and also recognizes
individuals with rare diseases as Persons With Disabilities (PWDs).

This status will help the patient’s family financially. Furthermore, the Philippine Society for Orphan
Disorders (PSOD) is a support organization situated in the Philippines that may provide medical and
financial support to ensure welfare and well-being of patients living with rare disorders, such as Hunter
syndrome, and their family.

Should there be any additional questions or concerns regarding the session, the family may contact the
counselors. Otherwise, the counselors should be open to meeting with them again on follow-up
appointments.

[DDD] Chiong MA, Berboso AG, Baluyot MM, Abacan MA. Results of clinical evaluations of Filipino
patients with mucopolysaccharidosis type II (Hunter Syndrome) in a one stop multidisciplinary clinic at
the Philippine General Hospital: A 3-Year experience. Acta Medica Philippina. 2013;47(1).
doi:10.47895/amp.v47i1.2017

[GGG]Chiong MA, Canson DM, Abacan MA, Baluyot MM, Cordero CP, Silao CL. Clinical, biochemical
and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - hunter syndrome.
Orphanet Journal of Rare Diseases. 2017;12(1). doi:10.1186/s13023-016-0558-0