Multiple sulfatase deficiency: clinical report and description of two novel mutations in a Brazilian patient.
Multiple Sulfatase Deficiency (MSD) is a rare autosomal recessive disease in which the activities of all sulfatases are reduced; its estimated prevalence is 1:1.4 million births. The disease is caused by mutations in SUMF1, which encodes an enzyme involved in the post-translational modification of sulfatases. The MSD phenotype is a combination of the clinical features found in diseases resulting from a deficiency of the individual sulfatases; i.e., mucopolysaccharidosis II, IIIA, IIID, IVA and VI, metachromatic leukodystrophy, X-linked ichthyosis, and the X-linked recessive form of chondrodysplasia punctata. We describe herein the first case of a Brazilian patient with MSD. The case was initially diagnosed as having mucopolysaccharidosis (MPS), due to skeletal alterations, coarse facial features, and urinary excretion of dermatan sulfate and heparan sulfate. Later, after a detailed biochemical investigation, the diagnosis of MSD was established. The analysis of the SUMF1 showed the patient was a compound heterozygote for two novel mutations (p.R349G and p.F244S). This case illustrates the challenges in the diagnosis of a disease considered rare, such as MSD. We point out that the availability of therapy for certain MPS disorders necessitates correct disease assignment, and the need to exclude the likelihood of MSD.
Artigalás
Osvaldo Alfonso
OA
Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
da Silva
Luiz Roberto
LR
Burin
Maira
M
Pastores
Gregory M
GM
Zeng
Bai
B
Macedo
Nívea
N
Schwartz
Ida Vanessa Doederlein
IV
D001921:Brain / Q000000981:diagnostic imaging; D001938:Brazil; D002675:Child, Preschool; D003871:Dermatan Sulfate / Q000652:urine; D003937:Diagnosis, Differential; D006497:Heparan Sulfate / Q000652:urine; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology; D008297:Male; D052517:Multiple Sulfatase Deficiency Disease / Q000201:enzymology / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013429:Sulfatases / Q000235:genetics*; D014057:Tomography, X-Ray Computed
D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013429:Sulfatases; C480483:SUMF1 protein, human
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