Multiple sulfatase deficiency

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Description from OMIM

Multiple sulfatase deficiency is an autosomal recessive inborn error of metabolism resulting in tissue accumulation of sulfatides, sulfated glycosaminoglycans, sphingolipids, and steroid sulfates. The enzymatic defect affects the whole family of sulfatase enzymes; thus, the disorder combines features of metachromatic leukodystrophy (250100) and of various mucopolysaccharidoses (see, e.g., MPS6; 253200). Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and ichthyosis. Different types of MSD can be distinguished according to the age of onset: neonatal, late infantile (0 to 2 years), and juvenile (2 to 4 years). Neonatal MSD is the most severe form with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. Late-infantile MSD, which includes the majority of cases, resembles late-infantile metachromatic leukodystrophy with progressive loss of mental and motor abilities and skeletal changes. There is also an attenuated form of late-infantile MSD with onset beyond the second year of life. Rare cases of juvenile-onset MSD have been reported with onset of symptoms in late childhood and slower progression (Blanco-Aguirre et al., 2001) (summary by Schlotawa et al., 2011).

Prevalence of clinical parameters (%)

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Number of patients in the reference Percent affected patients (Between 0 and 1, eg. 0.1 = 10%)
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List of symptoms

Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Mental retardation nervous 100 % 21224894 2011-10-27
Ichthyosis integumentary 100 % 21224894 2011-10-27
Mental retardation nervous 100 % 18509892 2011-11-15
Developmental delay nervous 100 % 18509892 2011-11-15
Hepatomegaly digestive 100 % 18509892 2011-11-16
Hyperactive reflexes nervous 100 % 18509892 2011-11-16
Babinski's sign nervous 100 % 18509892 2011-11-16
Splenomegaly circulatory 100 % 18509892 2011-11-16
Ichthyosis integumentary 100 % 18509892 2011-11-16
Seizures nervous 50 % 18509892 2011-11-15
Cerebral atrophy nervous 50 % 18509892 2011-11-16
Cerebellar atrophy nervous 50 % 18509892 2011-11-16
Leukodystrophy nervous 50 % 18509892 2011-11-16

List of references:

SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency.
Lars Schlotawa, Eva Charlotte Ennemann, Karthikeyan Radhakrishnan, Bernhard Schmidt, Anupam Chakrapani, Hans-Jürgen Christen, Hugo Moser, Beat Steinmann, Thomas Dierks, Jutta Gärtner,

Multiple Sulfatase Deficiency (MSD) is caused by mutations in the sulfatase-modifying factor 1 gene encoding the formylglycine-generating enzyme (FGE). FGE post translationally activates all newly synthesized sulfatases by generating the catalytic residue formylglycine. Impaired FGE function leads to reduced sulfatase activities. Patients display combined clinical symptoms of single sulfatase deficiencies. For ten MSD patients, we determined the clinical phenotype, FGE expression, localization and stability, as well as residual FGE and sulfatase activities. A neonatal, very severe clinical phenotype resulted from a combination of two nonsense mutations leading to almost fully abrogated FGE activity, highly unstable FGE protein and nearly undetectable sulfatase activities. A late infantile mild phenotype resulted from FGE G263V leading to unstable protein but high residual FGE activity. Other missense mutations resulted in a late infantile severe phenotype because of unstable protein with low residual FGE activity. Patients with identical mutations displayed comparable clinical phenotypes. These data confirm the hypothesis that the phenotypic outcome in MSD depends on both residual FGE activity as well as protein stability. Predicting the clinical course in case of molecularly characterized mutations seems feasible, which will be helpful for genetic counseling and developing therapeutic strategies aiming at enhancement of FGE.

European journal of human genetics : EJHG - Mar 2011

Multiple sulfatase deficiency in a Turkish family resulting from a novel mutation.
Uluç Yiş, Stefano Pepe, Semra Hiz Kurul, Andrea Ballabio, Maria Pia Cosma, Eray Dirik,

Multiple sulfatase deficiency (MSD) is an inherited lysosomal storage disease that affects post-translational activation of all of the sulfatases. Since biochemical and clinical findings are variable, the diagnosis is difficult in most of the cases. Missense, nonsense, microdeletion and splicing mutations in SUMF1 gene were found in all of the MSD patients analyzed. Here, we present clinical findings of two consanguineous patients with multiple sulfatase deficiency. They were found to be homozygous for a novel missense mutation c.739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.

Brain & development - May 2008