Multiple sulfatase deficiency - SUMF1 gene
Multiple sulfatase deficiency, also known as Austin syndrome or mucosulfatidosis, is a disease that primarily affects the brain, skin and skeleton. Because the signs and symptoms of the disease vary widely, it has been divided into three types: neonatal, late childhood and juvenile.
The neonatal type is the most severe form, and its signs and symptoms appear shortly after birth. Affected individuals have leukodystrophy, which may contribute to movement problems, seizures, developmental delay and slow growth. They also manifest dry skin, ichthyosis and hypertrichosis. Skeletal abnormalities may include scoliosis, joint stiffness and multiple dysostosis. Affected individuals may also have hearing loss, cardiac malformations and hepatosplenomegaly.
The late childhood type is the most frequent form of the disease. It is characterized by normal cognitive development in early childhood followed by psychomotor regression due to leukodystrophy or other brain abnormalities. People with this form of the disease don’t manifest as many signs and symptoms as people with neonatal type, but often have ichthyosis, skeletal abnormalities and coarse facial features.
The juvenile type is the rarest form of multiple sulfatase deficiency. Signs and symptoms of the juvenile type appear in mid or late childhood. As in the late childhood type, affected individuals have a normal cognitive development onset, but subsequently manifest psychomotor regression. In general, psychomotor regression in the juvenile type occurs at a slower rate than in the late childhood type. Ichthyosis is also common in this type.
Life expectancy is shortened in individuals with any type of multiple sulfatase deficiency. Typically, affected individuals survive only a few years after the signs and symptoms appear. However, life expectancy varies depending on the severity of the disease and how quickly the neurological problems get worse.
This process is due to mutations in the SUMF1 gene (sulfatase modifying factor 1), located on the short arm of chromosome 3 (3p26.1). This gene encodes the formylglycine generating enzyme (FGE). This enzyme is found in the endoplasmic reticulum, where it modifies sulfatase enzymes, which help the breakdown of sulfate-containing substances (such as sugars, fats and hormones). Specifically, FGE converts the amino acid cysteine into C-alpha-formylglycine.
At least 35 mutations in the SUMF1 gene responsible for the development of multiple sulfatase deficiency have been identified. Most genetic mutations change individual amino acids in the FGE enzyme, which greatly reduces the function of the enzyme or results in an unstable enzyme that decomposes rapidly. Sulfatases activity is impaired because the FGE enzyme modifies all known sulfatase enzymes. Sulfate-containing molecules that don’t break down build up in cells, which can cause cell death. The death of cells in some specific tissues, specifically the brain, skeleton and skin, lead to many of the signs and symptoms of this process. Mutations that generate a reduction in the function of the FGE enzyme are associated with the milder cases of the disease, while mutations that generate the synthesis of an unstable FGE enzyme tend to be associated with the most severe cases of multiple sulfatase deficiency.
This disease is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with multiple sulfatase deficiency, by means of the complete PCR amplification of the exons of the SUMF1 gene, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).