**Background:** Mucopolysaccharidosis type VII (MPS VII) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of β-glucuronidase, with an estimated frequency of 1/300,000 to 1/2,000,000. It presents with short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac and pulmonary disease, and cognitive impairment, resembling MPS I and II. A distinguishing feature is a history of nonimmune fetal hydrops. While some MPS VII patients with improved hydrops survive, survival with refractory fetal hydrops is rare. This report describes a case of severe fetal hydrops and refractory ascites diagnosed as MPS VII by whole-exome sequencing, discharged at 5 months after long-term ventilatory management.
**Methods:** This is a single case report from a tertiary neonatal intensive care unit. The patient was a male neonate born at 30 1/7 weeks' gestation by emergency cesarean section due to fetal distress, with a birth weight of 1,846 g (+2.4 SD) and Apgar scores of 2 at 1 minute and 5 at 5 minutes. Fetal hydrops was noted at 18 weeks, with subcutaneous edema, pleural effusions, and ascites; thoracoamniotic shunts were placed at 22 and 23 weeks. After birth, the patient received mechanical ventilation, inhaled nitric oxide (iNO), catecholamines, and hydrocortisone for circulatory failure and pulmonary hypertension (PH). Ascites was managed with an abdominal drain, prednisone, octreotide, and factor XIII preparation. Enteral feeding with medium-chain triglyceride (MCT) milk began at 28 days. Diagnostic workup included echocardiography, karyotyping, ascites cytology, maternal serology for TORCH infections, lymphatic scintigraphy, whole-body bone X-ray, and whole-exome sequencing of cord blood. Beta-glucuronidase activity in leukocytes and urinary uronic acid levels were measured.
**Key Results:** The patient had massive ascites (>100 mL/day until 3 days of age), pleural effusion, generalized edema, and coagulation abnormalities. PH improved, and iNO was discontinued at 5 days. Ascites gradually decreased at 3 weeks, the abdominal drain was removed at 32 days, and extubation occurred at 53 days. High-flow nasal cannula was changed to oxygen therapy from 92 days. At 96 days, lymphatic scintigraphy showed impaired lymphatic return to the central tract, with reaccumulation of ascites and massive scrotal edema. Echocardiography, renal and gastrointestinal imaging, karyotype (46, XY), ascites cytology, and maternal TORCH serology were normal. No hepatomegaly or ophthalmologic disease was noted, but bilateral severe hearing loss was present. Whole-body bone X-ray at 4 months showed oar-shaped rib deformity and punctate cartilage calcification. Whole-exome sequencing at 4 months revealed a compound heterozygous mutation in the GUSB gene. Beta-glucuronidase activity in leukocytes was low, and urinary uronic acid was high, confirming MPS VII. The patient was discharged at 5 months with home oxygen and gastric tube feeding. Enzyme replacement therapy started at 7 months resolved ascites and scrotal edema.
**Clinical Implications:** This case demonstrates that survival is possible in MPS VII with severe fetal hydrops and refractory ascites lasting over 5 months, contrary to previous reports where intractable effusions were often fatal. Key management strategies included lung-protective respiratory management (high-frequency oscillatory ventilation, iNO), careful fluid balance, and early enteral nutrition with MCT formula. The case highlights the difficulty of early clinical diagnosis of MPS VII, as facial features, rib deformities, and corneal opacity may appear late (rib deformity at 4 months, corneal opacity at 6 months). Only about one-third of MPS VII cases are diagnosed within the first year of life. Therefore, in cases of nonimmune fetal hydrops with refractory ascites, after excluding cardiac, renal, gastrointestinal, chromosomal, infectious, and malignant causes, early genetic testing (whole-exome or whole-genome sequencing) should be considered to identify MPS VII and enable timely enzyme replacement therapy.