Genetic basis of Mucopolysaccharidosis Type I in cats - is an autosomal recessive lysosomal storage disease caused by a specific mutation in the IDUA gene, which encodes the enzyme alpha-L-iduronidase. This enzyme is essential for the degradation of glycosaminoglycans (GAGs) such as dermatan sulfate and heparan sulfate. In affected cats, a 3 base-pair deletion mutation (c.1042_1044del) in the IDUA gene results in a deficient or nonfunctional enzyme. This defect leads to the accumulation of GAGs inside cells, causing progressive tissue damage and clinical signs of disease.
Pathophysiology - The absence or significant reduction of alpha-L-iduronidase prevents the proper breakdown of GAGs in lysosomes. The resulting accumulation of these macromolecules in multiple tissues leads to cellular dysfunction and widespread organ damage. This storage causes characteristic clinical signs including abnormalities in skeletal development, connective tissue, eyes, and heart.
Complications - Affected cats may exhibit: Broad, flat faces and large heads with small ears. Thickened skin on the neck. Abnormal gait due to skeletal deformities including broad cervical vertebrae and hip subluxation. Corneal opacity (clouding) causing vision impairment. Cardiac murmurs related to mitral valve insufficiency. Progressive loss of mobility and growth retardation.
Why This Matters to Breeders and Vets - Genetic Testing: DNA tests identifying the IDUA mutation allow breeders to detect carriers and avoid mating two carriers, preventing affected kittens. Early Diagnosis: Veterinarians can recognize typical clinical signs and confirm diagnosis with genetic tests, enabling early intervention and supportive care. Breed Health Management: Understanding the autosomal recessive inheritance pattern helps breeders make informed decisions to reduce disease prevalence and maintain healthy breeding populations. Welfare: Early recognition and prevention help reduce suffering caused by this progressive and ultimately fatal disorder.
Summary - Mucopolysaccharidosis Type I in cats is an inherited autosomal recessive lysosomal storage disease caused by a 3 base-pair deletion mutation in the IDUA gene, leading to deficiency of alpha-L-iduronidase enzyme. This enzymatic defect causes accumulation of glycosaminoglycans in tissues, resulting in skeletal abnormalities, corneal clouding, abnormal gait, and heart disease. Genetic testing supports breeders and veterinarians to prevent affected litters, diagnose early, and improve welfare for feline populations.