Makindo Medical Notes

Deficiency in lysosomal enzyme leads to improper breakdown of glycosaminoglycans, causing accumulation in various tissues. Dysostosis multiplex is characterized by hepatosplenomegaly, marked skeletal abnormalities, short stature, and deformities of the thoracic cage.

About

• Mucopolysaccharidoses (MPS): A group of inherited metabolic disorders caused by enzyme deficiencies affecting the breakdown of glycosaminoglycans (GAGs).
• Autosomal recessive inheritance pattern.
• Rare, with an incidence of less than 1 in 100,000.

Aetiology

• Iduronidase Deficiency: One of the key enzyme deficiencies, specifically in MPS type I (Hurler syndrome), leading to the buildup of dermatan sulfate and heparan sulfate in tissues.

Clinical Features

• Dysostosis multiplex: A combination of skeletal abnormalities, including short stature, thoracic cage deformity, and characteristic gibbous deformity of the spine.
• Mental retardation and developmental delays, often evident in early childhood.
• Corneal clouding: A hallmark of MPS, leading to vision impairment.
• Cardiac involvement: Progressive heart disease, which can be a major cause of morbidity.
• Life expectancy is often reduced, with death occurring in childhood or adolescence if untreated.
• Characteristic coarse facial features: Hepatosplenomegaly, enlarged tongue, and prominent forehead.

Investigations

• Genetic Testing: Identification of mutations in genes encoding lysosomal enzymes, such as IDUA (iduronidase gene) for MPS I.
• Urine Test: Detection of excess glycosaminoglycans in the urine can indicate the presence of MPS.
• Enzyme Assay: Measurement of enzyme activity in blood or fibroblasts can confirm the diagnosis.

Management

• Supportive Care: Includes interventions such as shunting for hydrocephalus, joint replacement for skeletal deformities, and respiratory support as needed.
• Enzyme Replacement Therapy (ERT): Available for certain types of MPS, such as laronidase for MPS I, which can slow disease progression.
• Physical therapy and regular monitoring of cardiac and respiratory function to manage complications.
• Bone marrow transplant may be considered in some cases, particularly in severe forms of MPS I.