Mucopolysaccharidosis (MPS) involves neurodevelopmental decline due to lysosomal dysfunction. Hematopoietic stem cell transplantation (HSCT) may modify disease progression, but subtype-specific outcomes remain unclear. Fifty-seven MPS patients (aged 1-8 years) undergoing HSCT in Shanghai (2019-2024) were assessed longitudinally using Griffiths Mental Development Scales-Chinese (GDS-C) pre-HSCT and at 3, 12, and 24 months post-HSCT. Linear mixed models evaluated timepoint, age, and subtype effects. HSCT significantly improved locomotor function (F = 111.57, p < 0.001), with greatest gains in MPS III (β = 59.57) and age-dependent decline (β =  - 2.46/year). Personal-social function improved modestly (F = 4.44, p = 0.039), while language/eye-hand coordination showed progressive gains (p ≤ 0.001). Subtype influenced language (F = 3.75) and coordination (F = 2.89), with attenuated responses in MPS II. No Timepoint × Subtype interactions suggested uniform temporal effects. HSCT stabilizes/improves neurodevelopment in MPS, modulated by subtype and transplant age. Early intervention optimizes outcomes, particularly for MPS III. Culturally adapted GDS-C enables precise monitoring, guiding HSCT timing and rehabilitation.

Mucopolysaccharidosis type II (MPS II) is a chronic inherited disease with multiorgan involvement, a progressive course, and restricted life expectancy. To evaluate the predictors of fatal outcomes in MPS II patients. In the retrospective cohort study, the clinical, laboratory data and enzyme replacement therapy (ERT) (84.2%) of about 160 patients were extracted and analyzed from the Russian MPS II registry, with death as a primary outcome. We compared patients who died (n = 20; 12.5%) with severe form (n = 13; 68.4%) and attenuated form (n = 6, 31.6%) to 140 alive patients. Fatal outcomes occurred in 5%, 35%, 20%, and 40% of patients before 10, 10-14, 15-19, and ≥ 20 years. The most common causes of death were cardiovascular (29.4%), respiratory failure (17.6%), including pneumonia (17.6%), and their associations (17.6%) and MPS II progression (11.8%). Acute or chronic respiratory failure was in 53%. Died patients had higher birth weight, higher age of diagnosis, and start of ERT. Hydrocephalus, hydrocephalus bypass surgery, epilepsy, difficulty swallowing, and impaired movement after 12 years of age were significantly more common in the deceased patients. Cox regression analysis has revealed the following time-dependent covariates of the lethal outcome: 1st-year psychomotor development delay, delayed mental and speech development, hydrocephalus, swallow disorders, impossible walking at age > 12 years, respiratory disorders, tracheostomy, neuronopathic form. Increased birth weight, delayed diagnosis and the start of ERT, and development of neuronopathic form with impossible walking after 12 years were the main predictors of the fatal outcome.

Allogeneic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for patients with mucopolysaccharidoses (MPS). We investigate the efficacy and improvements in the quality of life of HSCT in pediatric patients with MPS. A retrospective analysis of transplantation data from 46 cases of MPS from a single institution in China was conducted. The cohort of 46 patients included 9 cases of MPS I, 16 cases of MPS II, 15 cases of MPS IVA and 6 cases of MPS VI. The median age at diagnosis was 2.59 years. The median age at transplantation was 3.80 years. The median follow-up time was 3.1 years (range, 0.8-8.1 years) and 43 patients were alive. The incidence of grades II to IV aGVHD was 17.4%, wherein the incidence of grades III and IV aGVHD was 4.3%. The incidence of moderate-to-severe cGVHD was 6.5%. GAGs urinary excretion decreased and enzyme activity levels reached normal. After HSCT, multiple bone dysplasia, upper-airway obstruction and recurrent otitis media were significantly improved; vision, corneal clouding, cardiovascular disease, hepatosplenomegaly and hydrocephalus were improved or remained stable; neurological symptoms were improved or remained stable in most patients but progressed in others; the patients with MPS IH/S and MPS II reached nearly normal growth rate of height and weight. Meanwhile, the patients with MPS IH, MPS IVA and MPS VI remained poor growth after HSCT. The Activities of Daily Living (ADL) scores were improved in most patients with MPS. ADL scores in patients with severe phenotypes were lower than health control subjects and patients with attenuated phenotypes. HSCT is a good therapeutic option for MPS and improves the quality of life of patients. MPS patients with attenuated phenotypes provide a better outcome in ADL after HSCT.

Hunter syndrome is an X-linked recessive lysosomal storage disorder that is caused by a mutation in the iduronate sulfatase gene. Both anterior and posterior segment abnormalities are found as a result of the accumulation of glycosaminoglycans in ocular tissues. Retinal dystrophy, particularly rod-cone dystrophy, has a major effect on visual acuity, leading to significant visual impairment as the condition worsens. We report a case of a 53-year-old male patient of Asian descent previously diagnosed with Hunter syndrome, who presented with progressive difficulty in visual tracking and colour recognition. Fundus examination revealed bull's eye maculopathy in both eyes. Optical coherence tomography revealed severe attenuation of the outer retinal layers at the macula. Electrophysiological tests showed reduced photopic and scotopic responses, with P50 responses severely attenuated, and visual field testing showed a central scotoma in both eyes. Patients with Hunter syndrome can present with retinitis pigmentosa or rod-cone dystrophy. Accumulation of glycosaminoglycans in the retinal pigment epithelium results in photoreceptor loss, affecting both rods and cones. Maculopathy associated with rod-cone dystrophy may be associated with this condition.

We report a case of an eight-year-old boy with mucopolysaccharidosis (MPS) II with atypical skin lesions of hyperpigmented streaks along Blaschko's lines. This case presented with mild symptoms of MPS such as hepatosplenomegaly, joint stiffness, and quite mild bone deformity, which was the reason for the delay in diagnosis until the age of seven years. However, he showed an intellectual disability that did not meet the diagnostic criteria for an attenuated form of MPS II. Iduronate 2-sulfatase activity was reduced. Clinical exome sequencing of DNA from peripheral blood revealed a novel pathogenic missense variant (NM_000202.8(IDS_v001):c.703C>A, p.(Pro235Thr)) in the IDS gene, which was confirmed in the mother with a heterozygous state. His brownish skin lesions differed from the Mongolian blue spots or "pebbling" of the skin that are observed in MPS II.