The present study included the first case of mucopolysaccharidosis (MPS) type VII in Taiwan. During pregnancy, the patient was diagnosed with hydrops fetalis and had ascites aspiration 4 times. In the following years, she presented gradually with chronic lung disease, developmental delay, short stature, dysmorphic features of coarse face, macroglossia and pigeon chest with scoliosis. Upon referral at age 4 years, she had corneal clouding, mild limitation of range of motion (ROM) and hepatosplenomegaly. X-ray showed paddle ribs and dysplastic vertebral bodies. MPS was suspected and urine glycosaminoglycans (GAGs) elevated were noted. The leukocyte enzymatic analyses for MPS I, MPS II, MPS IIIB, MPS IVA, and MPS VI were all normal. Afterward, the molecular analysis showed two heterozygous genetic variants of c.104C > A and c.1454C > T in trans in the GUSB gene (NM_000181.4) which were the causes for MPS VII. Then, we checked the leukocyte β-glucuronidase activity for MPS VII and showed extremely low, therefore confirmed the diagnosis. Clinicians should increase the awareness on the early signs of MPS to have a prompt diagnosis and offer the correct treatment like enzyme replacement therapy (ERT) as early as possible.

We report a patient with mucopolysaccharidosis type VI, on long-term enzyme replacement home therapy. Results support the efficacy and safety benefits, with additional advantage of home therapy to minimize the risk of community-transmitted infections.

Enzyme replacement therapy (ERT) is one of the available therapies for mucopolysaccharidosis (MPS). This study presents a follow-up of two siblings with MPS IVA (Morquio A disease) that received ERT. Both siblings received weekly intravenous infusions of elosulfase alfa for 4.5 years. One sibling (patient 1, P1; male) started therapy at 54 months of age, and the other sibling (patient 2, P2; female) started at 11 months of age. ERT was well-tolerated. In comparison to P1, P2\'s growth curves deviated less from the norm. The orthopedic deformities of P1 were more severe than those of P2 and required several surgical corrections. P1\'s sleep test at 48 months revealed obstructive sleep apnea, while by the age of 102 months, parameters were normal. P2 never had sleep apnea. Only P1 demonstrated ear, nose, and throat clinical illnesses. In comparison to P1, P2\'s physical function was better maintained. In conclusion, ERT was safe in both patients during a 4.5-year follow-up. Although the typical characteristics of this disease were similar in both patients, P1 had a complex clinical course in comparison to P2, which influenced function and quality of life. Therefore, in order to make the most of ERT, it may be more beneficial when initiated at a relatively young age.

Mutations of the endoplasmic reticulum (ER)-stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS. Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS-/- mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.
All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by μCT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.
The proband, a boy with severe OI, had blue sclera and tooth agenesis. A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes. Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%); however, collagen I levels were only reduced in hOBs (5-10%). Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to life-long bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.
Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period. A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.