Multiple sulfatase deficiency (MSD) is a
lysosomal storage disease caused by a deficiency of
formylglycine-generating
enzyme due to SUMF1 defects. MSD may be misdiagnosed as
metachromatic leukodystrophy (MLD), as neurological and neuroimaging findings are similar, and
arylsulfatase A (
ARSA) deficiency and enhanced urinary
sulfatide excretion may also occur. While
ARSA deficiency seems a cause for neurological symptoms and later
neurodegenerative disease course, deficiency of other
sulfatases results in clinical features such as dysmorphism,
dysostosis, or
ichthyosis. We report on a girl and a boy of the same origin presenting with severe
ARSA deficiency and neurological and neuroimaging features compatible with MLD. However, exome sequencing revealed not yet described homozygosity of the missense variant c.529G > C, p.Ala177Pro in SUMF1. We asked whether dynamics of disease course differs between MSD and MLD. Comparison to a cohort of 59 MLD patients revealed different disease course concerning onset and
disease progression in both MSD patients. The MSD patients showed first gross motor symptoms earlier than most patients with juvenile MLD (<10th percentile of Gross-Motor-Function in MLD [GMFC-MLD] 1). However, subsequent motor decline was more protracted (75th and 90th percentile of GMFC-MLD 2 (loss of independent walking) and 75th percentile of GMFC-MLD 5 (loss of any locomotion)). Language decline started clearly after 50th percentile of juvenile MLD and progressed rapidly. Thus, dynamics of disease course may be a further clue for the characterization of MSD. These data may contribute to knowledge of natural course of ultra-rare MSD and be relevant for counseling and
therapy.