Abstract
Background : Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the GBA gene. This results in multisystem involvement, including hepatosplenomegaly, cytopenias, and bone disease. Type 1 GD is the most common form and typically lacks CNS involvement. Over 300 mutations in the GBA gene have been identified worldwide, with a few well-characterized variants. Among its various manifestations, GD may present with growth impairment—a nonspecific feature that can mimic growth hormone deficiency (GHD), and lead to diagnostic confusion. Early recognition and initiation of enzyme replacement therapy (ERT) are crucial to prevent irreversible complications and support normal development. In Saudi Arabia, a nationwide screening across 13 centers enrolled 390 patients with unexplained splenomegaly and/or thrombocytopenia; only one case was confirmed as GD, yielding a prevalence of 0.26% in this high-risk group. While ~75 patients have been diagnosed nationally (45 with type 1, 4 with type 2, and 26 with type 3), true prevalence is likely underestimated due to high consanguinity and diagnostic delays.
Case Presentation: We report a 9-year-old female initially diagnosed with idiopathic GHD in February 2024 due to short stature (< 3rd percentile) and low growth velocity (1.9 cm over 3 months). Bone age in July 2023 was 7 y 10 m compared to a chronological age of 8 y 8 m. Mid-parental height was 155 cm; Tanner stage was prepubertal. She was started on recombinant GH by an endocrinologist. In October 2024, she presented to our hospital with gastroenteritis, dehydration, and splenomegaly, prompting admission. During hospitalization, she had persistent bicytopenia: WBC 2.5-3.8×10⁹/L, Hgb 9.2-9.4 g/dL, PLT 71-115×10⁹/L, MCV 70-75 FL, MCH 23.1-23.5 pg and ferritin 233 ng/mL. Abdomen US revealed splenomegaly (14.6–15.6 cm). A hematology consultation was requested for further investigations. Bone marrow aspiration showed infiltration by large abnormal macrophages with a honeycomb appearance. Genetic testing confirmed a homozygous c.152G>T (p.Ser51Ile) mutation in GBA. This particular mutation is not among the globally common mutations associated with GD. Plasma Lyso-GL1, a specific and sensitive GD biomarker, was elevated at 747.3 ng/mL ( reference <14). The family history, initially undisclosed, revealed two paternal cousins diagnosed with GD. These results confirmed the diagnosis of Gaucher disease.
ERT with imiglucerase (50 mg/kg biweekly, later increased to 60 mg/kg) was initiated in November 2024. GH therapy was discontinued. A transient rash developed but resolved with antihistamines; no other notable side effects were observed. Lyso-GL1 levels declined to 407.3 ng/mL by Jan 2025 and 199.0 ng/mL by June 2025. Splenic size reduced to 11.5 cm. By July 2025, height reached 127.5 cm (5th–10th percentile), showing modest catch-up growth. Continued improvement is expected with ongoing therapy.
Discussion: This case highlights the diagnostic challenge of distinguishing GD from GHD in children presenting with isolated short stature. Chronic systemic illnesses can suppress the GH–IGF-1 axis, mimicking GHD. Early signs such as cytopenias or organomegaly should prompt investigation for underlying metabolic diseases. Misdiagnosis may delay appropriate treatment and expose patients to unnecessary GH therapy. A pedigree analysis of 23 family members revealed multiple affected individuals, including a sibling previously diagnosed with GHD, raising suspicion of undiagnosed GD. The p.Ser51Ile mutation identified in this family is rare globally but may represent a regionally relevant variant. Further research in Saudi Arabia is needed to evaluate its prevalence and clinical impact. Despite a positive family history, cultural stigma and paternal resistance initially delayed the screening of at-risk relatives. This case underscores the importance of repeated family history assessments, genetic counseling, and addressing social barriers to testing.
Conclusion: GD can present as isolated growth failure, mimicking GHD. Clinicians should consider systemic or metabolic causes in cases of unexplained short stature or cytopenias. Early diagnosis, targeted screening, and prompt initiation of ERT improve outcomes in GD. Despite the rarity of the identified mutation, further investigation is warranted in Saudi Arabia due to the high consanguinity rate and the presence of social stigma, which may delay diagnosis.
