Hydrocephalus as a rare clinical symptom in a patient with multiple sulfatase deficiency

Multiple Sulfatase Deficiency (MSD) is a rare inherited autosomal recessive disorder of metabolism. MSD is caused by mutations in the sulfatase- modifying- factor 1 (sumf1) -gene, encoding the formylglycine-generating enzyme (FGE). FGE posttranslationally modifies newly synthesized sulfatases and an impaired FGE function results in the release of less active or inactive sulfatases leading to lysosomal storage and other pathologies related to impaired sulfatase function. Clinical symptoms of MSD therefore are a combination of different single sulfatase deficiencies, among them neurodegeneration and neurological signs similar to metachromatic leukodystrophy, dysmorphism and hepatosplenomegaly resembling mucopolysaccharidosis and an ichthyotic skin rash like in X- linked ichthyosis. Clinically neonatal cases could be distinguished from late infantile and juvenile forms of MSD.

We present a now 6 months old boy with developmental delay, slight dysmorphic signs, hepatosplenomegaly and ichthyosis. An MRI showed an external and internal hydrocephalus, although his head circumference was normal. He was first treated with a ventriculostomy. Due to progressive hydrocephalus a ventriculo- peritoneal shunt was implanted afterwards. Diagnostic work-up for lysosomal disorders revealed that the activities of different sulfatases were reduced in lymphocytes and skin fibroblasts of the patient, molecular analysis revealed a homozygous mutation in the sumf1- gene. The combination of hydrocephalus and dysmorphic features of a lysosomal storage disorder is already known for mucopolysaccharidoses. Besides, multiple sulfatase deficiency should also be considered and is an important differenzial diagnosis.