Galactosialidosis

Galactosialidosis is a rare, inherited lysosomal storage disorder that affects multiple body systems, with symptoms and life expectancy varying significantly based on the age of onset.

Overview

Galactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.

Early Infantile Form

Infants with this form are typically diagnosed between birth and 3 months of age and usually live to around 6 months. Features include:

• Extensive swelling caused by fluid accumulation before birth (hydrops fetalis)
• A soft out-pouching in the lower abdomen
• Enlarged liver and spleen (hepatosplenomegaly)
• Abnormal bone development (dysostosis multiplex)
• Enlarged heart (cardiomegaly)
• An eye abnormality called a cherry-red spot
• Kidney disease that can progress to failure

Late Infantile Form

Symptoms typically begin around 2 years of age. This form is characterized by:

• Short stature
• Dysostosis multiplex
• Hepatosplenomegaly
• "Coarse" facial features
• Intellectual disabilities
• Hearing loss
• Cherry-red spot

Juvenile/Adult Form

Symptoms typically begin around age 16, though the age of onset varies widely. This form is associated with a nearly normal life expectancy and includes:

• Difficulty coordinating movements (ataxia)
• Muscle twitches (myoclonus)
• Seizures
• Intellectual disabilities that worsen over time
• Dark red spots on the skin (angiokeratomas)
• "Coarse" facial features
• Cherry-red spot
• Vision loss and hearing loss

Causes

Variants in the CTSA gene cause all forms of galactosialidosis. This gene provides instructions for making a protein called cathepsin A, which is active in cellular compartments called lysosomes. Cathepsin A works with other enzymes to form a complex that breaks down sugar molecules attached to proteins or fats. It also plays a role in the formation of elastic fibers in the extracellular matrix.

CTSA gene variants interfere with the normal function of cathepsin A, causing other enzymes to become non-functional or break down prematurely. This leads to the accumulation of substances within the lysosomes, characteristic of this family of lysosomal storage disorders.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder. Parents of an affected individual typically carry one copy of the altered gene but do not show signs or symptoms.