Multiple sulphatase deficiency presenting at birth

Abstract

A new case of multiple sulphatase deficiency with onset at birth is described. The patient had many dysmorphic features and hydrocephalus, similar to one other case with early onset described in the literature. The new patient differed from the other case in having chondrocalci‐ficans congenita, heart abnormalities and an abnormal fold of tissue present between the laryngeal inlet and the oesophagus. Excessive mucopolysacchariduria was present and there was profound deficiency of all sulphatases examined in plasma, leucocytes and cultured skin fibroblasts.

Neonatal manifestation of multiple sulfatase deficiency

“…The phenotype of neonatal MSD has been documented only rarely in detail [3,16]. The classic and more frequent form of MSD presents after the age of 1 year with neurological findings due to arylsulfatase A deficiency and mild signs of mucopolysaccharidoses [2].…”

“…Based on the degree of severity and age of onset, neonatal, moderate, and mild types of MSD have been differentiated. So far, the neonatal form of MSD has been described in detail only in two patients [3,16]. MSD is caused by loss-of-function mutations in SUMF1 (sulfatase modifying factor 1 gene), which encodes the protein formylglycine-generating enzyme (FGE) involved in post-translational modification at the catalytic site of all sulfatases [5,9].…”

Molecular analysis ofSUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency

“…The clinical symptoms overlap with those described for known single sulfatase deficiencies like metachromatic leukodystrophy, mucopolysaccharidoses, X-linked ichthyosis and chondrodysplasia punctata type I [Hopwood and Ballabio, 2001]. The neonatal form is characterized by a coarse face, cataract and hydrocephalus resembling mucopolysaccharidosis, whereas later onset forms are closer to infantile or juvenile metachromatic leukodystrophy with often normal early development followed by psychomotor impairment and a neurodegenerative course [Burch et al, 1986;Perlmutter-Cremer et al, 1981;Kepes et al, 1988].…”

SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency

“…Our neonatal patient exhibited the whole range of symptoms possible, which agrees with all published neonatal cases. [5][6][7][8] Most symptoms were present at birth and the patient showed a rapidly progressive course of disease. The group of late infantile patients 9,11,12 included in this study could be clearly distinguished from the neonatal patient, as symptoms varied in their age of onset with some features presenting only in later life or others lacking completely.…”

“…According to the few published cases, all neonatal MSD patients died within the first year of life. [5][6][7][8] Late infantile MSD resembles late infantile metachromatic leukodystrophy with progressive loss of mental and motor abilities; these clinical features are combined with other symptoms of single sulfatase deficiencies like dysmorphism, skeletal changes and ichthyosis. 2,3,[9][10][11][12] Late infantile MSD can be subdivided into a severe (LIS) and an attenuated (late infantile mild, LIM) form, the latter showing a reduced number of symptoms and later onset beyond the second year of life.…”