Our aim is the early detection of mucopolysaccharidosis (MPS) by examining the radiographs taken for reasons other than a metabolic disease, such as infection, trauma, and short stature. The radiographs of children who applied to outpatient and emergency clinics in our hospital between 01/01/2022 and 31/12/2022 were examined by a pediatric radiologist retrospectively without knowledge of patient information. The MPS enzyme panel and urine glycosaminoglycan analysis were performed in patients having dysostosis multiplex on radiographs. In cases with MPS detected by enzyme and urine analysis, the definitive diagnosis was confirmed by genetic analysis. Skeletal radiographs of 15.104 cases admitted to our hospital were examined (11,270 chest x-ray, 314 lumbosacral spine x-ray, 2970 hand x-ray, 253 pelvis x-ray, 162 skull x-ray, and 135 complete skeletal surveys). In 67 children, dysostosis multiplex was observed in the skeletal X-ray. Among them, seven newly diagnosed MPS cases were detected. Three cases were diagnosed with MPS type 4A, two with MPS type 6, one with MPS type 2 and one with MPS type 3B. Age at diagnosis was 46.2 ± 30.6 months (range; 20-111 months). There was a history of consanguinity in 6 (85.7%) cases. Radiographs can provide clues for diagnosing MPS before the clinical findings become prominent in children admitted to the hospital for other complaints. Therefore, X-ray screening can be performed on children in endemic regions of MPS to search for dysostosis multiplex.

The necessity of early treatment for lysosomal storage diseases (LSDs) has triggered the development of newborn screening for LSDs in recent years. Here we report the first 70,000 newborns screened for Mucopolysaccharidosis (MPS) type 4A (Morquio syndrome) and other LSDs by an 8-plex assay including the original 4-plex LSD screening tandem mass spectrometry (MS/MS) assay for Pompe disease, Fabry disease, Gaucher disease, and MPS I disease. The additional reaction for MPS II, MPS 3B, MPS 4A, and MPS 6 enzymes was performed separately from the 4-plex reaction. The two reactions were quenched and extracted, then combined before carrying out a single 2-min UPLC-MS/MS analysis. From Mar. 2018 to Apr. 2019, 73,743 newborns were screened with the 8-plex LSD screening assay. The 8-plex assay revealed a better analytical precision than the previous 4-plex assay possibly because the 8-plex was carried out using UPLC-MS/MS. Six newborns were found to have low MPS-4A enzyme (N-acetylgalactosamine-6-sulfatase) activity and biallelic GALNS pathogenic mutations in trans; these patients are presumably affected with MPS4A, making an incidence of one in 12,291 (95% confident interval (CI): 5633-26,817). One mutation, c.857C > T (p.T286 M) of the GALNS gene, accounted 5 of the 12 mutated alleles. These newborns had immature vertebral bodies at 1 month of age, and one case was treated with elosulfase alfa 2 mg/kg/week starting from 4 months of age. Among other MPSs screened, one case of MPS I, 3 cases of MPS II, and 3 cases of MPS 3B were detected. One case of mucolipidosis type III was also diagnosed. In conjunction with another 9 patients of Pompe disease, Gaucher disease, and classical Fabry disease, making an incidence of LSDs as one in 3206 newborns (95% CI: 2137 - 4811). The one with infantile-onset Pompe disease and the one with Gaucher disease were treated since the age of 8 days and 41 days respectively. Routine newborn screening of MPS 4A and other LSDs were made possible by the 8-plex LSD screening assay. However, detailed phenotype prediction and the time to start treatment will need further elucidation.

A 6-year-old Syrian boy presented with complaints of facial dysmorphism and difficulty of walking. He had coarse face, macrocephaly, pectus carinatum, x-bain deformity, kyphosis, corneal clouding, and claw hand deformity. Galactose-6 sulphatase enzyme level was 0.1 nmol/mg.17 h (reference range, > 68 nmol/mg.17 h), compatible with Morquio syndrome. On laboratory examinations, potassium level was 2.9 mmol/L (reference range, 3.5 mmol/L to 5.1 mmol/L), sodium level was 130 mmol/L (reference range, 135 mmol/L to 148 mmol/L), and chloride level was 92 mmol/L (reference range, 101 mmol/L to 109 mmol/L). Blood pH was 7.5 and bicarbonate level was 31 mEq/L. Urine sodium and chloride levels were high. Arterial blood pressure was normal and these findings were consistent with Bartter syndrome. This is the first report of a patient with the association of Bartter syndrome and mucopolysaccharidosis type 4A, which was thought to be coincidental.