Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder that occurs due to impaired activity of all known sulfatase enzymes - mucopolysaccharidosis II (Hunter syndrome), IIIA (Sanfilippo syndrome A), IIID (Sanfilippo syndrome D), IVA (Morquio syndrome A) and VI (Maroteaux-Lamy syndrome), metachromatic leukodystrophy, X-linked ichthyosis and X-linked recessive chondrodysplasia punctata. (Online Mendelian Inheritance in Man number - 272200).
This disease has an autosomal recessive pattern of inheritance. It affects both, males and females and has an estimated prevalence of 1 in 1,000,000 live births.
This disease has an autosomal recessive pattern of inheritance. It affects both, males and females and has an estimated prevalence of 1 in 1,000,000 live
When do we suspect Multiple sulfatase deficiency?
The clinical features are those associated with deficiencies of the single sulfatase enzymes noted above and combines features of metachromatic
leukodystrophy and of various mucopolysaccharidoses
There are four clinical forms classified on the age of presentation:
1. Severe neonatal form - Onset in the first months of life with coarse facies, cataract and hydrocephalus.
2. Severe late-infantile form of MSD - Onset within the first year of life with neuroregression similar to late-infantile metachromatic leukodystrophy.
3. Mild-late onset MSD - Onset between 2 years and 4 years with coarse facies, hepatosplenomegaly, dysostosis multiplex, cardiomyopathy and slowly
progressive neuroregression with leukodystrophy. This is the commonest presentation.
4. Juvenile MSD – Ichthyosis and intellectual disability. Rare presentation
How is MSD diagnosed?
High index of suspicion is important
1. Clinical suspicion in a child with coarse facies, neuroregression, hepatosplenomegaly and ichthyosis
2. Urinary excretion of mucopolysaccharides
3. A deficiency of several sulfatase enzymes (arylsulfatase A, B, and C, two steroid sulfatases and four other sulfatases) occurs. These can be tested in a
4. Molecular analysis of SUMF1 gene – 4 ml blood in EDTA vacutainer is required for this testing. It is also helpful to send the blood sample of the
parents for carrier testing and confirmation of the mutations identified in the affected patient.
What are the treatment options available?
Symptomatic and supportive therapy and monitoring for possible complications
How to prevent the birth of a child with MSD?
1. Parents of a child with MSD are carriers. They will never develop any disease manifestations.
2. For a couple with one child with MSD, or those who are identified to be carriers, there is a 25% risk of recurrence in each pregnancy.
3. Prenatal diagnosis by chorionic villus sampling and molecular analysis for the familial mutation is performed at 11 weeks of gestation.
4. Carrier testing by molecular analysis of siblings of the parents of an affected child should be offered. They have a 50% of being carriers.
When to contact a Medical Professional?
5. When a diagnosis of MSD is made
6. When pregnancy is planned in a family with history of MSD disease
Who to contact for more information?
7. The Department of Health Research and Indian Council of Medical Research have constituted a National Task Force to perform a multicentric collaborative
study at different research institutes across the country. Further information can be found at http://www.icmrmetbionetindia.org/task-force-disoredrs.php