IllnessSulfatase deficiency, multiple; differential diagnosis

NGS +

Multiple sulfatase deficiency is a disease that mainly affects the brain, skin and skeleton. Symptoms vary widely and are divided into three types, neonatal, late infantile and juvenile. The neonatal type is the most severe, occurring shortly after birth. Affected individuals have leukodystrophy with movement disorders, seizures, developmental delay, slow growth, ichthyosis and hypertrichosis as well as scoliosis and dysostosis multiplex. The patients may further present with coarse facial features, hearing loss, cardiac malformations and hepatosplenomegaly. The late-infantile type is the most common with initially normal cognitive development followed by psychomotor regression. Ichthyosis is often observed with skeletal abnormalities and coarse facial features. The juvenile type is the rarest form with symptoms in middle to late childhood. Affected individuals also experience slow psychomotor regression. Life expectancy is shortened in all three types. Multiple sulfatase deficiency is caused by mutations in the SUMF1 gene. Most mutations severely limit the function of the encoded enzyme, rarely resulting in an unstable protein. Mutations leading to reduced enzyme function are associated with the less severe symptoms. The disease is inherited in an autosomal recessive manner. The DNA diagnostic yield is unknown. The differential diagnosis includes other causes of leukodystrophies, progressive neurodegeneration and hepatosplenomegaly. Combination genetic and biochemical testing is advised with measurements of at least three sulfatases.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK538937/

• Alias: Mucosulfatidosis
• Alias: Sulfatidosis, juvenile, Austin type
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2V (NAGLU)
• Allelic: Retinitis pigmentosa 73 (HGSNAT)
• Alexander disease (GFAP)
• Allelic: Parkinson disease 24, AD, susceptibility to (PSAP)
• Canavan disease (ASPA)
• Chondrodysplasia punctata, XLR (ARSL)
• Combined SAP deficiency (PSAP)
• Fucosidosis (FUCA1)
• GM1-gangliosidosis, type I, II, III (GLB1)
• GM2-gangliosidosis, several forms (HEXA)
• Gaucher disease, atypical (PSAP)
• Hex A pseudodeficiency (HEXA)
• Ichthyosis, XL (STS)
• Krabbe disease (GALC)
• Krabbe disease, atypical (PSAP)
• Metachromatic leukodystrophy (ARSA)
• Metachromatic leukodystrophy due to SAP-b deficiency (PSAP)
• Mucolipidosis II, III alpha/beta (GNPTAB)
• Mucopolysaccharidosis II (IDS)
• Mucopolysaccharidosis IVA (GALNS)
• Mucopolysaccharidosis Ih, Ih/s, Is (IDUA)
• Mucopolysaccharidosis type IIIA, Sanfilippo A (SGSH)
• Mucopolysaccharidosis type IIIB, Sanfilippo B (NAGLU)
• Mucopolysaccharidosis type IIIC, Sanfilippo C (HGSNAT)
• Mucopolysaccharidosis type IIID (GNS)
• Mucopolysaccharidosis type IVB, Morquio (GLB1)
• Mucopolysaccharidosis type VI (Maroteaux-Lamy (ARSB)
• Multiple sulfatase deficiency (SUMF1)
• Sandhoff disease, infantile, juvenile + adult forms (HEXB)
• Tay-Sachs disease (HEXA)
• Usher syndrome, type IV (ARSG)