Saudi variant of multiple sulfatase deficiency

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Multiple sulfatase deficiency (MSD), also known as Austin's disease, is a rare lysosomal storage disorder.
• Classic MSD presents with neonatal, childhood, or juvenile onset, characterized by a broad spectrum of clinical and biochemical abnormalities.

Observation:

• Eight patients with a unique phenotypic presentation of MSD were identified, with onset in childhood.
• These patients exhibited mucopolysaccharidosis-like somatic and facial features, corneal cloudiness, macrocephaly, severe dysostosis multiplex, and gibbus.
• Distinctly, they lacked ichthyosis, retinal degeneration, severe deafness, severe mental retardation, and dementia, differentiating them from classic MSD.

Findings:

• The primary neurological issue was cervical cord compression due to axis abnormalities.
• Neuroradiologic findings showed white-matter changes, but the presentation was not typical of metachromatic leukodystrophy.
• Sulfatase deficiencies were intermediate between classic juvenile and childhood-onset MSD, with steroid sulfatase activity spared in most cases.
• This Saudi variant constitutes 5% of lysosomal storage diseases in the Inborn Errors of Metabolism Laboratory's registry.

Implications:

• This discovery expands the phenotypic spectrum of multiple sulfatase deficiency.
• It highlights the importance of recognizing this specific Saudi variant for accurate diagnosis and management.
• Further research into the genetic and biochemical underpinnings of this variant may offer insights into MSD pathogenesis.