**Background:** Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of α-L-iduronidase, leading to accumulation of glycosaminoglycans (GAGs) such as dermatan and heparan sulfate. It affects approximately 1 in 100,000 population. MPS I is classically divided into three phenotypes: Hurler syndrome (severe), Hurler-Scheie syndrome (intermediate), and Scheie syndrome (attenuated). Clinical manifestations include coarse facial features, skeletal abnormalities (dysostosis multiplex), corneal clouding, cardiac involvement, respiratory issues, and neurocognitive impairment. Early diagnosis and treatment, including hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT), can improve outcomes.
**Methods:** This is a case report of a 15-year-old male who presented to a tertiary care center in Nepal with shortness of breath for 12 hours, headache for 3 hours, and one episode of abnormal body movements with loss of consciousness. The patient had a history of obstructive hydrocephalus, recurrent seizures, and respiratory problems since age 3. He had undergone herniotomy for a right congenital inguinal hernia at 18 months. Developmental milestones were normal until age 3. He attended school up to 5th grade with poor performance and left due to diminished vision and seizures. No consanguinity was reported. Physical examination revealed dolichocephaly, macrocephaly, short neck, corneal clouding, joint stiffness, coarse facial features (depressed nasal bridge, flared nostrils, ocular hypertelorism, dental malocclusion, thick lips), and height < -3 SD for age. Vital signs: BP 100/60 mmHg, HR 148 bpm, RR 38 breaths/min, temperature 98.2°F. Respiratory exam showed bilateral equal air entry with left infra-axillary and infra-scapular crepitations. Abdomen was soft with an umbilical stump and liver palpable 3 cm below costal margin (span 10 cm). Investigations: CBC, LFTs, RFTs normal. Echocardiography showed moderate mitral stenosis (MS), mild to moderate mitral regurgitation (MR), and moderate tricuspid regurgitation (TR). Radiographs: lateral skull showed inverted J-shaped sella turcica; hand/wrist showed bullet-shaped phalanges with proximal pointing of metacarpals; lateral spine showed thoracolumbar kyphosis; AP hips showed acetabular dysplasia. Urine GAG excretion and blood α-L-iduronidase enzyme activity could not be performed due to unavailability. The patient was admitted to PICU with CPAP (PEEP 8 cm H2O) for 43 hours, then maintained room air saturation but had occasional obstructive sleep apnea with SpO2 86-88% during sleep. Sodium valproate was used for seizures. Neurosurgery consultation for hydrocephalus was refused by family.
**Key Results:** The patient was diagnosed with MPS I, Hurler-Scheie phenotype based on clinical features (coarse facies, corneal clouding, skeletal abnormalities, mild cognitive impairment) and radiological findings (inverted J-shaped sella, bullet-shaped phalanges, thoracolumbar kyphosis, acetabular dysplasia). The patient had moderate MS, mild to moderate MR, and moderate TR on echocardiography. At follow-up, the child required intermittent oxygen support for respiratory difficulties, remained on valproate for seizures (seizure-free at follow-up), and other MPS I features were not improving.
**Clinical Implications:** This case underscores the diagnostic challenges of MPS I in resource-limited settings where confirmatory enzyme and urine tests are unavailable. Diagnosis relies on clinical and radiological features. Early recognition is crucial for genetic counseling and timely intervention. HSCT before age 2 and before cognitive impairment is the gold standard for severe MPS I, but is not feasible in low-income countries. ERT with laronidase can improve physical and respiratory function but does not cross the blood-brain barrier. Symptomatic management (respiratory support, anticonvulsants, surgical interventions for hydrocephalus, carpal tunnel release) remains the mainstay. Genetic counseling for at-risk couples is essential to prevent recurrence.