Growth charts of Sanfilippo patients, created in a German study, can help doctors predict the developmental progress of children affected by this rare disease, and counsel parents on what to expect, the researchers said.
The charts, which show growth patterns of people with Sanfilippo syndrome from birth to early adulthood, also will provide a baseline for researchers to help evaluate the impact of therapeutic strategies as they are developed.
The researchers’ findings were reported in the study “Growth charts for patients with Sanfilippo syndrome (Mucopolysaccharidosis type III),” published in the journal Orphanet Journal of Rare Diseases.
Mucopolysaccharidosis (MPS) type III, also known as Sanfilippo syndrome, refers to a group of rare, lysosomal storage disorders caused by a deficiency in the enzymes involved in the degradation of heparan sulfate — a naturally produced molecule used by the body to form bones, cartilage, skin, and tissues.
Marked by developmental delays that start during early childhood, children with MPS III experience a deterioration of neurological and motor functions.
Although it has been recognized that adults with MPS III are generally short in stature, there is no clear description of patients’ physical development over time. Available data also is inconclusive, with reports varying from normal to delayed growth.
To address this knowledge gap, a team led by researchers at the pediatrics department of University Medical Center Hamburg-Eppendorf (UKE), in Germany, documented the development of 182 MPS III patients, and used the data to create growth reference charts.
“Disease-specific growth charts are important tools for tracking growth and recognizing deviations from normal,” the researchers said. They noted that, with such information, doctors “are able to counsel parents with regard to growth expectations.”
The team examined the height, weight, head circumference, and body mass index of all patients from birth until age 21. Signs of puberty also were assessed by interviewing the children’s parents.
The study included 96 males and 86 females, of whom 135 were diagnosed with MPS IIIA, 34 with MPS IIIB, and 11 with MPS IIIC. Two patients had an unclassified type of MPS III.
Researchers built growth charts for the different parameters assessed, and compared them with reference growth data from the long-term German KiGGS study, part of Germany’s countrywide health monitoring program. The Robert Koch Institute (RKI) has been running the “German Health Interview and Examination Survey for Children and Adolescents” (KiGGS) since 2003.
Collected data revealed that, at birth, the height and weight of Sanfilippo patients was within the normal range.
However, at the age of 2, both boys and girls with MPS III were significantly taller than children without the disease, and male patients were taller at age 4. Their growth pace was comparable to healthy children until boys reached 4.5 years, and girls reached age 5, after which their growth began to slow down. By 18, both genders were significantly shorter than people without Sanfilippo.
The causes for short stature and altered growth patterns in MPS III are not completely understood, researchers noted. Some studies suggest these symptoms result from a combination of several alterations in bone formation and bone maturation, as well as abnormalities in hormone production.
Analysis of weight and body mass index showed similar trends to those seen in height. At ages 2 and 4, both genders were heavier than healthy children. However, by age 18, they weighed significantly less. On average, males with MPS III weighed 52.9 kg (116.6 lbs), while healthy males weighed 71.4 kg (157.4 lbs). Females with Sanfilippo weighed an average 49.8 kg (109.7 lbs), while those without the disorder weighed 60.1 kg (132.5 lbs).
At birth, head circumference of infants with the disease also was found to be within normal values. But it became larger during the children’s first two years, and then remained bigger until the patients reached physical maturity.
However, the team noted that, due to the small amount of data available from ages 5 to 17, they could not accurately calculate significant differences between patients and healthy children within this period.
Researchers also found no significant differences in growth patterns between patients with MPS IIIA, B or C.
The charts presented in this study “contribute to the understanding of the natural history of MPS III,” the researchers said, noting that there currently is no treatment for Sanfilippo.
“Specific growth charts represent an important tool for families and physicians as the expected height at physical maturity can be estimated and therapeutic effects can be monitored,” they said.