Unveiling Gaucher Disease: A Rare Cause of Acute Respiratory Failure in Toddlers

Abstract

Gaucher disease (GD) is an uncommon lysosomal storage disease resulting from glucocerebrosidase deficiency, causing glucocerebroside accumulation in macrophages. It classically occurs with hepatosplenomegaly, anemia, thrombocytopenia, and skeletal involvement. In a few cases, it can present with acute respiratory failure, making early diagnosis and management challenging. The case of a toddler who had severe respiratory distress and was misdiagnosed as a primary pulmonary pathology is presented here. By thorough investigations, such as enzyme assays and genetic analysis, a clear diagnosis of Gaucher disease was made. Early detection of unusual presentations of GD, such as respiratory complications, is important for timely intervention and better outcomes.

Introduction

Gaucher disease is the most prevalent lysosomal storage disease, inherited in an autosomal recessive pattern because of GBA1 gene mutations. It has a wide range of clinical presentations from asymptomatic to dangerous, life-threatening complications. Three main subtypes are Type 1 (non-neuronopathic), Type 2 (acute neuronopathic), and Type 3 (chronic neuronopathic). The classical picture includes hepatosplenomegaly, hematologic findings, and skeletal features, but pulmonary features, particularly acute respiratory failure, are an underdiagnosed feature.

This case illustrates an atypical presentation of Gaucher disease in a toddler who develops acute respiratory distress, reinforcing the need for consideration of metabolic diseases in the differential diagnosis of acute respiratory failure in children.

Case Report

A 2-year-old boy was admitted to the pediatric intensive care unit (PICU) with acute respiratory failure. He had a history of repeated respiratory infections, failure to gain weight, and increasing abdominal distension over the last few months. No family history of genetic disorders was significant.

On presentation, the child was tachypneic with intercostal retractions and oxygen saturation of 85% on room air. There was hepatosplenomegaly, with a hard liver edge palpable 4 cm below the costal margin and an enlarged spleen reaching the pelvis. Cardiovascular and neurological examinations were normal.

Differential Diagnosis and Initial Management

Given the presentation of respiratory distress with hepatosplenomegaly, initial differentials included:

• Viral or bacterial pneumonia

• Pulmonary embolism

• Congenital heart disease

• Hematologic malignancies (e.g., leukemia, lymphoma)

• Storage disorders such as Gaucher disease or Niemann-Pick disease

Initial laboratory investigations revealed:

• Hemoglobin: 8.2 g/dL (low)

• White blood cell count: 12,500/mm³ (normal)

• Platelet count: 78,000/mm³ (low)

• Serum ferritin: Elevated

• Acid phosphatase: Elevated

Chest X-ray showed bilateral ground-glass opacities with interstitial thickening, suggesting an infiltrative or metabolic process rather than a primary infectious etiology. A high-resolution CT scan revealed diffuse reticulonodular opacities with signs of pulmonary hypertension.

Due to persistent hypoxemia despite supportive oxygen therapy, an extensive metabolic workup was initiated.

Confirmatory Diagnosis of Gaucher Disease

A peripheral blood smear revealed characteristic "Gaucher cells," large macrophages with a rumpled tissue paper appearance. The enzyme assay revealed significantly decreased beta-glucocerebrosidase activity, which confirmed the diagnosis. Genetic testing revealed a homozygous pathogenic variant in the GBA1 gene, consistent with Type 1 Gaucher disease. Bone marrow biopsy also showed lipid-laden macrophages, confirming the diagnosis.

Discussion

Pulmonary involvement in Gaucher disease, though uncommon, can be severe, presenting with progressive interstitial lung disease, pulmonary hypertension, or acute respiratory distress. The underlying mechanism involves:

1. Accumulation of Gaucher Cells in Pulmonary Capillaries – Leading to impaired gas exchange.

2. Inflammatory Cytokine Release – Contributing to fibrosis and pulmonary hypertension.

3. Hematologic Complications – Resulting in anemia-induced hypoxia and secondary respiratory dysfunction.

In this case, the severe respiratory distress was initially mistaken for primary pneumonia, delaying a metabolic diagnosis. The presence of hepatosplenomegaly and cytopenias provided crucial diagnostic clues.

Management and Treatment

Once diagnosed, the patient was started on:

1. Enzyme Replacement Therapy (ERT) – Recombinant imiglucerase was initiated at a standard dose of 60 U/kg every two weeks.

2. Supportive Respiratory Care – Oxygen supplementation and diuretics for pulmonary hypertension.

3. Hematologic Support – Regular monitoring of anemia and thrombocytopenia.

Over 6 months, the patient demonstrated significant clinical improvement, with reduced hepatosplenomegaly and resolution of respiratory symptoms.

Challenges in Diagnosis

Several factors contributed to the delayed diagnosis of Gaucher disease in this patient:

• Atypical Presentation: Initial respiratory symptoms masked the underlying metabolic disorder.

• Overlapping Features with Other Diseases: Gaucher disease shares clinical manifestations with infectious and hematologic conditions.

• Limited Awareness Among Clinicians: Metabolic disorders are often overlooked in acute respiratory failure cases.

Future Directions and Considerations

• Early Screening Programs: Incorporating lysosomal storage disorder panels in neonates with unexplained organomegaly and anemia.

• Advancements in Gene Therapy: Ongoing research explores gene-editing technologies to correct the underlying GBA1 mutation.

• Multidisciplinary Approach: Collaboration between pediatric pulmonologists, geneticists, and hematologists is essential for optimal patient outcomes.

Conclusion

This case highlights the significance of including Gaucher disease among the differential diagnoses for toddlers who are admitted with acute respiratory failure and hepatosplenomegaly. A keen index of suspicion, coupled with timely metabolic testing, is necessary for early detection and treatment. Enzyme replacement therapy is still the cornerstone of treatment and can dramatically alter prognosis in affected children. Increased awareness of unusual presentations of Gaucher disease will enable early diagnosis and improved clinical outcomes.