PracticeUpdate Conference Series_WORLDSymposium 2019

Neuroimaging Demonstrates Complications in

Newborns With MPS I Abnormalities have been shown in infants <6months of age with the disease.

N euroimaging assessments of infants <6 months of age with muco- polysaccharidosis (MPS) I have demonstrated abnormalities. Recognition of such features could be a useful tool for assessing severity, report fndings pre- sented at the WORLDSymposium 2019. Elizabeth Braunlin, MD, of the University of Minnesota in Minneapolis, and colleagues reviewed MRI images from 12 infants <6 months of age with known severe MPS I for features known to be present in severe MPS I. These included perivascular space enlargement, enlarged extra-axial spaces, white matter lesions, ventriculomegaly, bony abnormalities of the skull and cer- vical spine, cervical cord stenosis, and odontoid capping. Additionally, dilated optic nerve sheaths and mastoid uid were noted when present. Six male infants were studied at a median of 76 (21–185) days. A total of 6 infants had begun enzyme replacement therapy a median of 13 (range 2–87) days prior to imaging. No infant exhibited a normal scan. Bony abnormalities of the skull (12/12), the presence of mastoid uid (12/12) and enlarged perivascular spaces (10/12) were the most common findings. Enlarged extra-axial spaces (8/12) and cervical spi- nal canal stenosis (8/12), enlarged optic nerves (6/11), ventriculomegaly (7/12), and odontoid capping (7/12) occurred in 50% of infants.

White matter lesions (0/12) and cortical atrophy 0/12) were not identified. Infants <6 months of age with severe MPS I exhibit neuroimaging findings known to be present in older children with MPS I, most commonly bony abnormalities of the skull and enlarged perivascular spaces. Evaluation of a comparable group of infants with attenuated MPS I infants will be crucial before employing these find- ings as part of the assessment of disease severity in unknown mutations. Dr. Braunlin explained that newborn screening for MPS I allows for initiation of early treatment for infants with known mutations. In those with unknown mutations, treat- ment strategies become complicated as early enzyme replacement therapy may alter clinical findings subtly, preventing the identification of infants with severe muta- tions requiring hematopoietic stem cell transplantation. Recognizing features of severe mutations by neuroimaging could be a useful tool for classifying severity.

Dr. Braunlin also examined the hypothe- sis that with implementation of newborn screening for MPS I in the US, hemato- poietic stem cell transplantation may now occur earlier than 1–2 years of age and cardiac issues might be fewer. She and her team reviewed their records for any MPS I-H infant who underwent hematopoietic stem cell transplantation at ≤6 months of age. Pre- and (most recent) post-hematopoi- etic stem cell transplantation cardiac echocardiograms and clinical courses were reviewed in all infants with MPS I-H undergoing hematopoietic stem cell transplantation at ≤6 months of age. Overall, 7 infants with MPS I-H (4 males) were diagnosed at median MEDRNG 14 (range 3–22) days of life by newborn screening (n=2) or because an older sibling suffered from MPS I-H (n=5), and began enzyme replacement therapy at MEDRNG 48 (range 7–62) days of life.

" …early cardiac evaluation will identify cardiac features; however, increased awareness of the anatomic and functional differences of all organ systems related to young age will be necessary for optimal outcomes in patients with MPS I-H. "

PRACTICEUPDATE CONFERENCE SERIES • WORLDSymposium 2019 6