mucopolysaccharidosis II

Mucopolysaccharidosis Type II (MPS II): A Rare Genetic Disorder

Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare genetic disorder that affects many different parts of the body. It occurs almost exclusively in boys, although it has been reported in a few girls.

Characteristics and Symptoms

• The condition is characterized by an abnormal accumulation of glycosaminoglycans (GAGs) in various organs and tissues.
• Symptoms can include:
  • Distinctive facial features
  • Large head size
  • Hydrocephalus
  • Enlargement of the liver and spleen (hepatosplenomegaly)
  • Umbilical or inguinal hernia
  • Hearing loss
  • Mental retardation
  • Abnormal skeletal development
• The severity of the disease depends on the phenotype, with some individuals experiencing a more severe form of the disorder.

Causes and Inheritance

• MPS II is caused by a lack of the enzyme iduronate-2-sulfatase.
• It is inherited in an X-linked recessive pattern, meaning that inheriting a single defective gene from the mother can result in mucopolysaccharidosis in a son.

Age of Onset and Progression

• The age of onset varies among affected individuals, with some experiencing symptoms at birth or early childhood.
• The rate of progression also varies significantly among affected males, with some experiencing a more rapid decline in health.

References:

• [1] MPS II is characterized by an abnormal accumulation of glycosaminoglycans (GAGs) in various organs and tissues. [2]
• [3] Symptoms can include distinctive facial features, large head size, hydrocephalus, enlargement of the liver and spleen (hepatosplenomegaly), umbilical or inguinal hernia, hearing loss, mental retardation, abnormal skeletal development. [13]
• [4] MPS II is caused by a lack of the enzyme iduronate-2-sulfatase. [12]
• [5] It is inherited in an X-linked recessive pattern, meaning that inheriting a single defective gene from the mother can result in mucopolysaccharidosis in a son. [12]

Mucopolysaccharidosis Type II (MPS II) Signs and Symptoms

Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare genetic disorder that affects multiple systems in the body. The signs and symptoms of MPS II can vary in severity and may include:

• Coarsening of facial features: Children with MPS II often have distinctively large facial features, including full lips, large rounded cheeks, broad nose, and an enlarged tongue [8][9].
• Enlargement of vocal cords: This can cause a deep, hoarse voice in affected individuals [7][8].
• Joint stiffness: People with MPS II may experience joint stiffness, particularly in the hands, which can lead to restricted movement [12][13].
• Corneal clouding: Some types of mucopolysaccharidoses, including MPS II, can cause corneal clouding [12].
• Progressive intellectual delay: Children with Hurler syndrome, a type of mucopolysaccharidosis, may experience progressive intellectual delay [12].
• Cardiovascular signs and symptoms: Individuals with MPS II often have cardiovascular signs and symptoms, including murmurs related to valvular disease (in order of frequency: mitral, aortic, tricuspid) [14].

Age of Onset

The age of onset for MPS II can vary, but symptoms typically begin to appear in children between the ages of 2 and 4 years old [6][11]. In some cases, symptoms may become apparent as early as 18 months or as late as 6 years old.

Inheritance Pattern

MPS II is inherited in an X-linked recessive pattern, meaning that it primarily affects males. Females can be carriers of the disease but are less likely to experience severe symptoms [3][5].

It's essential to note that the severity and progression of MPS II can vary significantly among affected individuals. Early diagnosis and treatment can help manage symptoms and improve quality of life.

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9 [10] Context result 10 [11] Context result 11 [12] Context result 12 [13] Context result 13 [14] Context result 14

Treatment Options for Mucopolysaccharidosis Type II

Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, is a rare genetic disorder that affects the body's ability to break down and recycle sugar molecules. The condition is caused by a deficiency of the enzyme iduronate-2-sulfatase.

Current Treatment Options

According to recent studies [1], current treatments available for MPS II include:

• Intravenous Enzyme Replacement Therapy (ERT): This involves administering an intravenous solution containing the deficient enzyme, iduronate-2-sulfatase. One specific ERT product, Elaprase (idursulfase), has been licensed in the United States by the FDA since 2006 [9].
• Hematopoietic Stem Cell Transplantation (HSCT): This is a surgical procedure that involves replacing the bone marrow with healthy stem cells.
• Anti-inflammatory treatment: This may be used to manage symptoms such as pain and inflammation.

Effectiveness of Treatment

Clinical trials have shown that administration of ERT within 12 months from starting therapy can improve clinical parameters in patients with MPS II [2]. Additionally, a phase III trial demonstrated the efficacy of idursulfase in older, attenuated MPS II individuals [5].

Availability of Treatments

ERT is approved for use in several countries, including the United States, European Union, and others [8]. However, it's essential to note that access to these treatments may vary depending on geographical location and healthcare systems.

References:

[1] Stapleton, M. (2017). Current treatments available are intravenous enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), anti-inflammatory treatment, and ...

[2] Żuber, Z. (2023). Clinical trials showed that administration of enzyme replacement therapy within 12 months from starting therapy improved clinical parameters in ...

[5] McBride, KL. (2020). Idursulfase (Elaprase) is an intravenous enzyme replacement therapy (ERT) for MPS II that has been licensed in the United States by the FDA since 2006.

[8] May 6, 2024 — Enzyme replacement therapy (ERT) is approved in the United States, European Union, and several other countries for patients with MPS I, MPS II, ...

[9] McBride, KL. (2020). Idursulfase (Elaprase) is an intravenous enzyme replacement therapy (ERT) for MPS II that has been licensed in the United States by the FDA since 2006.

Differential Diagnosis of Mucopolysaccharidosis II (Hunter Syndrome)

Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. The differential diagnosis of MPS II involves distinguishing it from other conditions that may present with similar symptoms.

Key Differential Diagnoses:

• Mucopolysaccharidosis Type III (Sanfilippo syndrome): This is another type of mucopolysaccharidosis, characterized by the accumulation of glycosaminoglycans in cells. However, MPS III typically presents with a later age of onset and different clinical features compared to MPS II.
• Mucopolysaccharidosis Type I (Hurler syndrome): This is another type of mucopolysaccharidosis, caused by the deficiency of alpha-L-iduronidase. While both MPS I and MPS II present with similar symptoms, such as coarse facial features and joint abnormalities, they have distinct biochemical and genetic characteristics.
• Sotos syndrome: This is a rare genetic disorder characterized by excessive growth during childhood. However, Sotos syndrome typically presents with different clinical features compared to MPS II, such as macrocephaly and developmental delays.

Diagnostic Algorithm:

A differential diagnosis algorithm for MPS has been proposed (Cimaz et al.). Newborn infants with MPS often have radiological evidence of bone and joint abnormalities, which can aid in the early detection of these disorders. The importance of surgical history in diagnosing mucopolysaccharidosis type II (Hunter syndrome) has also been highlighted.

Genetic Considerations:

MPS II is an X-linked recessive disorder, primarily affecting males. However, a small number of females can be affected due to autosomal X-chromosomal translocation and nonrandom X-chromosome inactivation. The carrier status of the mother determines the recurrence risk to the family and can be accurately determined by molecular testing.

Biochemical Diagnosis:

A biochemical protocol for diagnosing mucopolysaccharidosis and its subtypes has been established (Fateen et al.). This involves analyzing urine free glycosaminoglycans using mass spectrometry-based analysis. The results of this analysis can aid in the differential diagnosis of MPS II from other types of mucopolysaccharidosis.

Conclusion:

The differential diagnosis of Mucopolysaccharidosis II (Hunter syndrome) involves distinguishing it from other conditions that may present with similar symptoms. A combination of clinical, radiological, and biochemical findings can aid in the accurate diagnosis of MPS II.