Stem Cell Transplant Helped Girl with Sanfilippo, Case Study Shows

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by Steve Bryson PhD |

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An 11-year-old girl with Sanfilippo syndrome type A who received a stem cell transplant as an infant maintained her cognitive skills and motor function, and improved her quality of life compared to six children who did not have the transplant, a case study reports.

In the absence of treatment options or participation in clinical trials, stem cell transplants given at an early stage of the disease may be considered. 

The study, “Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group,” was published in the journal Molecular Genetics and Metabolism Reports.

Sanfilippo syndrome type A (also known as mucopolysaccharidosis type IIIA, MPSIIIA) is characterized by mutations in the SGSH gene, which leads to a deficiency in the enzyme sulfamidase and causes the toxic buildup of a complex sugar known as heparan sulfate (a glycosaminoglycan).

While there are no approved treatments available, several clinical trials are investigating the effectiveness of enzyme replacement therapy to replace the missing sulfamidase, or gene therapy, which provides the genetic instructions to produce the enzyme. 

An alternative strategy is to transplant a type of healthy donor stem cells called hematopoietic stem cellswhich can give rise to all different types of blood cells including red blood cells and white blood cells of the immune system. Given through intravenous infusion, these new donor cells grow and secrete the enzyme making up for the deficiency. 

A few studies have reported trying this approach, but the results were mixed. However, reports about using hematopoietic stem cell transplantation (HSCT) in children with Sanfilippo syndrome are scarce. 

In this report, a team of German researchers describe the case of an 11-year old girl with Sanfilippo syndrome who received HSCT at the age 2.5  years. The team compared her clinical outcome with the medical histories of six children (three boys, three girls), ranging in age from 4 to 15s, who carried the same Sanfilippo-causing mutations (R74C and R245H) in the SGSH gene, but who had not received an HSCT transplant.

Three of the children were treated with genistein supplement, which is thought to reduce the levels of heparan sulfate in the body and the brain. 

The girl was born after 38 weeks of gestation and she developed normally in the first year of life. At 18 months of age, she was admitted to the hospital due to gastroenteritis (intestinal inflammation) and pneumonia. She has an overly large head (macrocephaly), an enlarged liver (hepatomegaly), and high levels of urinary glycosaminoglycan — a hallmark of the condition. Enzymatic testing and genetic analysis confirmed a diagnosis of Sanfilippo syndrome. 

Because no other treatment options existed at that time, and she was still very young, the parents chose to pursue the stem cell transplant. The procedure was well-tolerated with no serious complications (such as rejection of the new cells) and her sulfamidase activity and urinary glycosaminoglycan levels became normal. 

By age 11, although she was developing slowly, the girl showed no signs of regression. She could run, jump, and climb, as well as engage in daily living activities with little support, such as eating, drinking, dressing, and using the toilet. Although she slept well, she had several behavioral problems such as hyperactivity, aggressiveness, temper tantrums, and compulsive behavior. These symptoms improved upon treatment with antipsychotic medications. 

Using the four-point scoring system (FPSS), which measures motor function, speech abilities, and cognitive function, a total disability score was calculated for the girl as well as the six untreated patients as a comparison. While the untreated children showed a continuous decline in motor, cognitive, and speech abilities, the girl, while exhibiting some delays in speech and displaying cognitive impairment, did not show signs of regression in motor or cognition. 

A neurocognitive development assessment was carried out by parent interview using the Vineland Adaptive Behavior Scale (VABS-II), which generated age-equivalent scores. At 11 years, the girl showed the highest age-equivalent score of 51 months (4.25 years) compared to the untreated patients who scored between eight and 29 months (2.4 years). 

“This score is considerably higher than expected from the natural course in rapidly progressing MPS IIIA disease,” the researchers wrote.

Behavior was examined to identify 12 different Sanfilippo behavioral patterns including hyperactivity, aggressiveness, anxious behavior, whining, chewing, and stereotyped behavior, among others. The girl exhibited seven of the 12  typical behavioral patterns, while the untreated children averaged 9.3 behavioral patterns. Unlike most of the untreated children, the girl showed neither chewing nor whining behavior. 

Although the girl had sleep problems up to age 5, afterward they resolved, unlike the untreated group, in which most showed severe sleep abnormalities with regular awakenings. The girl also did not develop seizures, while four of the six untreated children developed epileptic seizures.

The girl’s frequent diarrhea in infancy stopped after HSCT compared to all other patients who continued to experience diarrhea.

“In conclusion, our transplanted patient presented with maintained cognitive skills, preserved motor function and improved quality of life suggesting a positive impact of HSCT on the natural course of the disease,” the researchers wrote.

“HSCT performed at an early stage of the disease could be considered in patients where other treatment options or participation in clinical trials are not available,” the researchers wrote.