Sanfilippo Growth Impairments Milder Than Other MPS Types

Children with mucopolysaccharidoses begin to show slowdowns after age 2

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Sanfilippo mucopolysaccharidoses | Sanfilippo Syndrome News | news illustration

Children with Sanfilippo syndrome have impaired growth compared with the general population, but these deviations are milder than those observed with other types of mucopolysaccharidoses (MPS), a study found.

The study, which spanned more than 30 years, found that children with MPS were significantly longer than healthy children at birth and generally showed good growth during early childhood, after which it slowed down to varying degrees.

The study, “Comparison of growth dynamics in different types of MPS: an attempt to explain the causes,” was published in the Orphanet Journal of Rare Diseases.

Mucopolysaccharidoses are a group of inherited disorders marked by deficiencies in enzymes needed to break down glycosaminoglycans (GAGs), a family of complex sugar molecules. Such deficiencies lead to toxic deposits forming and accumulating in various cells and tissues.

MPS can be categorized into seven clinically distinct forms (and numerous subtypes) that vary in age of onset, symptoms, and severity.

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MPS type III, also known as Sanfilippo, is caused by the absence or reduced activity of one of four enzymes involved in the breakdown of a GAG called heparan sulfate, which leads to progressive and severe neurodegeneration when it accumulates.

In general, MPS leads to profound disruptions to normal growth and development, but the growth trajectories of children with different MPS types appear to differ.

“Better understanding of the natural history of the disease can be achieved with long-term observations, which help detect and establish patterns of growth and physical development in the evaluated group,” the researchers wrote.

Growth across MPS types

Researchers at the Children’s Memorial Health Institute, Warsaw, Poland evaluated observational growth data from 1989 to 2020 from children with MPS seen at their institute to better understand growth dynamics across types.

Data from 195 patients ranging in age from 3 months to 18 years were analyzed. The most common MPS type was Sanfilippo, affecting 72 (36.9%) children (33 girls and 39 boys). Birth length and weight were taken from the children’s health records, and growth was monitored periodically for each child.

Results showed MPS growth patterns significantly differed from reference values in the general population. Across all MPS types, body lengths at birth were significantly greater than in the general population. Girls with Sanfilippo also had a significantly higher birth body weight relative to healthy babies.

Children with MPS continued to be generally taller than children in the general population until age 2, after which their growth started to slow.

But the trajectories of stunted growth diverged across MPS types with Sanfilippo linked to the mildest impairments and MPS type IVA, known as Morquio A syndrome, with the most severe deficits.

Heights relative to children in the general population were referred to in percentiles. If a child is in the 50th percentile, that means they’re taller than half of the children in the general population of the same age and sex, or are at the median.

Children with Sanfilippo continued to exceed the 50th percentile at age six, after which their growth began to slow, with heights dropping below the median for age- and sex-matched children in the general population. Some growth acceleration was seen between age 9 and 14 in these patients, which the researchers attributed to puberty.

Growth declines in children with Sanfilippo were notably slower than for all other MPS types; they were the last to reach the third height percentile, which is often used as the cutoff to define short stature.

Given that each MPS type is caused by deficits in different enzymes, the distinct type and degree of GAG accumulation may contribute to differences in growth trajectories, the researchers said.

For example, while heparan sulfate is the only GAG building up in Sanfilippo, other MPS types are marked by the buildup of additional GAGs, such as dermatan sulphate, which could lead to more severe impairments.

These findings highlight that “mean values for MPS patients’ birth length were statistically significantly greater than in the general population,” the researchers wrote, and that in childhood, their “growth is good (except MPS IVA), then takes a hit and slows down.”

“The age of exceeding the 3rd percentile is various for different MPS types and depends on disease severity,” they said, noting that more research is needed to support their findings even though their study analyzed a large number of patients.

“This could be important for future research that would document changes in growth patterns for children who have access to enzyme replacement therapy,” the researchers said.