Intrafamilial variability in the clinical manifestations of mucopolysaccharidosis type II: Data from the Hunter Outcome Survey (HOS)

Abstract

Several cases of phenotypic variability among family members with mucopolysaccharidosis type II (MPS II) have been reported, but the data are limited. Data from patients enrolled in the Hunter Outcome Survey (HOS) were used to investigate intrafamilial variability in male siblings with MPS II. As of July 2015, data were available for 78 patients aged ≥5 years at last visit who had at least one affected sibling (39 sibling pairs). These patients were followed prospectively (i.e., they were alive at enrollment in HOS). The median age at the onset of signs and symptoms was the same for the elder and younger brothers (2.0 years); however, the younger brothers were typically diagnosed at a younger age than the elder brothers (median age, 2.5 and 5.1 years, respectively). Of the 39 pairs, eight pairs were classified as being discordant (the status of four or more signs and symptoms differed between the siblings); 21 pairs had one, two, or three signs and symptoms that differed between the siblings, and 10 pairs had none. Regression status of the majority of the developmental milestones studied was generally concordant among siblings. Functional classification, a measure of central nervous system involvement, was the same in 24/28 pairs, although four pairs were considered discordant as functional classification differed between the siblings. Overall, this analysis revealed similarity in the clinical manifestations of MPS II among siblings. This information should help to improve our understanding of the clinical presentation of the disease, including phenotype prediction in affected family members.

Clinical characteristics and surgical history of Taiwanese patients with mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS)

“…The Hunter Outcome Survey (HOS) is a large, global, multicentre, observational registry (Shire, Lexington, MA, USA; NCT 03292887) that was initiated in 2005. The registry collects long-term data on patients with MPS II and the efficacy and safety of ERT with idursulfase [ 5 , 6 , 12 , 16 – 32 ]. Data from patients in Taiwan have been entered in the registry since 2012.…”

The youngest pair of siblings with Mucopolysaccharidosis type IVA to receive enzyme replacement therapy to date: A case report

“…Since Patients A and B carry identical GALNS gene variants, similar phenotypes would be expected (Morrone et al, 2014; Muthukumar Ramalingam et al, 2017). However, it must be noted that intrafamilial variability has been previously described in male siblings with MPS type II and it is possible that it also played a role in the growth outcomes observed in our pair of siblings (Ficicioglu et al, 2018). Specifically, Patient B's skeletal involvement was milder compared to his older brother at the time of treatment, as shown by his skeletal survey obtained shortly after birth (Figure 2b) and also by his physical exam findings throughout the years (Figure 3b‐1,b‐2); in contrast, Patient A presented pectus carinatum, kyphoscoliosis, and reduced extension of the right lower extremities since infancy (Figure 3a‐2,a‐3,a‐4).…”

Mucopolysaccharidosis Type II: A Kenyan Case Series

“…This has been suggested for the differences between siblings. After looking at the clinical presentations at different ages, Ficicioglu et al concluded that the chronological age difference between siblings may not have been the cause of discordance [ 13 ]. In our study, the sibling who was least affected was the youngest at 3 years.…”

“…He snored while awake and asleep and was not aware of his surroundings. The Japanese study associated frameshift mutation with severe disease [ 13 ].…”