SNP Shot: Genomic Insights

Mucopolysaccharidosis type I (MPS I) is a systemic disorder impacting various parts of the body. Historically, it was classified into three syndromes based on severity: Hurler syndrome (MPS I-H, the most severe), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S, the least severe). However, due to substantial overlap between these syndromes, MPS I is now categorized into severe and attenuated forms.

Infants with MPS I may appear normal at birth, though some present with an umbilical hernia (a bulge near the belly button) or an inguinal hernia (a bulge in the lower abdomen). Individuals with severe MPS I usually exhibit other symptoms within the first year of life. Those with the attenuated form display milder symptoms that manifest later in childhood.

Signs and symptoms of MPS I can include an enlarged head (macrocephaly), fluid accumulation in the brain (hydrocephalus), heart valve problems, distinctive "coarse" facial features, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged tongue (macroglossia). Enlargement of the vocal cords can lead to a deep, hoarse voice. Some individuals experience airway narrowing, resulting in frequent upper respiratory infections and pauses in breathing during sleep (sleep apnea).

Corneal clouding is common in individuals with MPS I, potentially causing significant vision impairment. Hearing loss and recurring ear infections may also occur.

Short stature and joint contractures, limiting mobility, can develop. Individuals with the severe form often exhibit dysostosis multiplex, characterized by multiple skeletal abnormalities visible on X-rays. Carpal tunnel syndrome, causing numbness, tingling, and weakness in the hands and fingers, frequently occurs. Spinal stenosis in the neck can compress and damage the spinal cord.

While both severe and attenuated MPS I affect diverse organs and tissues, severe MPS I is marked by a decline in cognitive function and faster disease progression. Developmental delay is usually evident by age 1, leading to loss of functional skills (developmental regression). Lifespan is often shortened, sometimes only extending into late childhood. Individuals with attenuated MPS I typically live into adulthood and may have a normal lifespan. Some have learning disabilities, while others have normal intellectual function. Heart disease and airway obstruction are major causes of death in both types of MPS I.

Inheritance:

MPS I follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must carry mutations for the condition to develop. Parents of an affected individual each carry one copy of the mutated gene but usually do not exhibit any signs or symptoms of the disorder themselves.