A Case Report of a Japanese Boy with Morquio A Syndrome: Effects of Enzyme Replacement Therapy Initiated at the Age of 24 Months

Abstract

Background: Morquio A syndrome, mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disorder caused by the deficient activity of N-acetylgalactosamine-6-sulfatase (GalNac6S), due to alterations in the GALNS gene. This disorder results in marked abnormalities in bones and connective tissues, and affects multiple organs. Here, we describe the clinical course of a Japanese boy with MPS IVA who began enzyme replacement therapy (ERT) at the age of 24 months. Patient: the patient presented for kyphosis treatment at 22 months of age. An X-ray examination revealed dysostosis multiplex. Uronic acids were elevated in the urine and the keratan sulfate (KS) fraction was predominant. The leukocyte GalNac6S enzyme activity was extremely low. The patient exhibited the c.463G > A (p.Gly155Arg) mutation in GALNS. Based on these findings, his disease was diagnosed as classical (severe) Morquio A syndrome. An elosulfase alfa infusion was initiated at the age of 24 months. The patient’s body height improved from −2.5 standard deviation (SD) to −2 SD and his physical activity increased during the first 9 months on ERT. However, he gradually developed paralysis in the lower legs with declining growth velocity, which required cervical decompression surgery in the second year of the ERT. The mild mitral regurgitation, serous otitis media, and mild hearing loss did not progress during treatment. Conclusion: early initiation of the elosulfase alfa to our patient showed good effects on the visceral system and muscle strength, while its effect on bones appeared limited. Careful observation is necessary to ensure timely surgical intervention for skeletal disorders associated with neurological symptoms. Centralized and multidisciplinary management is essential to improve the prognosis of pediatric patients with MPS IVA.

A 9-Month-Old with Skeletal Abnormalities and a Consanguineous Sibling with Mucopolysaccharidosis IVA: The Role of Urinary Glycosaminoglycan Testing in Disease Diagnosis and Treatment Monitoring

“…The height of the patient featured in this case report exceeds the average height of MPS IVA patients as seen in Figure 4 ; 3 however, she was diagnosed with a GHD. The incidence of GHD in individuals with MPS IVA is not well reported in the literature, 25 , 26 possibly due to the difficulty in evaluating patient height and growth related to the skeletal abnormalities that are associated with MPS IVA or the delayed onset of puberty in MPS IVA patients. For monitoring patients diagnosed with MPS IVA, with the approval of elosulfase alfa to reduce the severity of MPS IVA symptoms, regular urine GAG quantification is commonly used to monitor the effects of ERT in reducing urinary KS concentration.…”

Foramen magnum stenosis in patients with mucopolysaccharidoses: diagnosis and surgical treatment. Review of literature

“…В настоящее время проводятся клинические исследования по оценке эффективности интратекального введения через систему Ommaya при ЗФТ. ТГСК является стандартом лечения пациентов с МПС I типа в возрасте до 2 лет или без поражения ЦНС и обеспечивает терапевтический эффект у пациентов с МПС II, IVA, VI и VII типов, особенно при лечении на ранней стадии заболевания [41].…”

“…ЗФТ сопряжена с необходимостью еженедельных инъекций, ввиду короткой циркуляции препарата в крови и ограниченного проникновения в очаги поражения костного аппарата и ЦНС. ТГСК является более эффективным методом, однако может применяться не у всех пациентов из-за ограниченной доступности подходящих доноров и риска Том 4 № 2 2024 смертности, обусловленного реакцией «трансплантат против хозяина», инфекционными заболеваниями и рядом других осложнений [41]. Nakamura-Utsunomiya A. и коллеги показали, что у ребенка с МПС IVA типа в течение второго года ЗФТ развилась компрессия СМ на уровне С1 позвонка с последующей нестабильностью атлантоаксиального сустава.…”

Tracheal Resection for Critical Airway Obstruction in Morquio A Syndrome

“…Thanks to enzyme replacement therapy (ERT), individuals with Morquio A syndrome are living longer after earlier initial diagnosis and treatment [ 2 ]. The benefits of ERT on skeletal dysplasia progression are less clear-cut than those seen in the viscera [ 3 , 4 ], but the ability to carry out orthopaedic interventions may be limited by the presence of airway and spinal cord compromise. Tortuous distortion and compression of the trachea advances over time, and patients experience worsening dyspnoea and opisthotonos (severe cervical hyperextension), as well as progressive vertebral abnormalities and instability, and development of spinal cord compression—this combination of issues particularly impacts quality of life and remains the leading cause of death for patients with Morquio A syndrome [ 5 ].…”