**Background:** Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder (incidence 1/76,000) characterized by bone marrow dysfunction (typically neutropenia), exocrine pancreatic insufficiency, and skeletal dysplasia. The advent of genetic testing has revealed a broader phenotypic spectrum than previously recognized. Early diagnosis in infancy is challenging because classic features are often absent. This report describes an atypical early-onset SDS presentation with unusual clinical, laboratory, and imaging findings that delayed diagnosis.
**Methods:** A female infant born at 37+6 weeks via vaginal delivery after an uneventful pregnancy to nonconsanguineous parents was small-for-gestational-age (birth weight 2090 g, −3.77 SD; length 47 cm, −1.15 SD; OFC 32 cm, −1.59 SD). At 2 months of age, she presented with pallor and tachycardia at a routine evaluation. Blood tests showed severe anemia (Hb 6.9 g/dL), and she was admitted for red blood cell transfusion. On admission, she had no dysmorphic features but showed extrauterine growth retardation (weight 2840 g, −4.19 SD). Laboratory evaluation revealed normocytic anemia with low reticulocyte count, normal platelet and white blood cell counts, and an absolute neutrophil count of 1060/mmc. Peripheral blood smear, Coombs test, hemolysis indices, urine analysis, fecal occult blood, viral PCR (Parvovirus B-19, enteroviruses, herpetic viruses), T. pallidum serology, and iron studies were normal. Abdominal ultrasound showed a small pancreas with reduced thickness (particularly body and tail), abnormal echogenicity, and a 'damaged' appearance. Abdominal MRI with T2-weighted Turbo-Spin-Echo Multi-Vane sequences and selective fat suppression confirmed reduced pancreatic parenchyma without fat infiltration or calcification. Pancreatic function testing revealed fecal elastase <15 μg/g (normal >200 μg/g), indicating severe insufficiency. A sweat test was normal (41 mmol/L, normal <50 mmol/L), and CFTR gene testing was initiated. During hospitalization, Hb improved slowly with persistent reticulocytopenia; one sample showed neutropenia (neutrophil range 500–1937/mmc). SBDS gene analysis was performed. Chest radiograph showed 11 ribs bilaterally. Coagulation studies, serum calcium, phosphorus, and alkaline phosphatase were normal. The infant was discharged after 24 days weighing 3354 g (−4.15 SD) on vitamin and trace element supplementation, without gastrointestinal symptoms.
**Key Results:** Genetic testing revealed no CFTR mutations but identified homozygosity for the exon 2 mutation c.258+2 T > C in the SBDS gene, confirming SDS. The authors compared this case with five previously reported SDS cases diagnosed before 3 months of age. Common features across cases included small-for-gestational-age status, anemia, and pancreatic insufficiency. Unlike most prior cases, this patient had isolated anemia without persistent neutropenia, no thrombocytopenia, no gastrointestinal symptoms, no recurrent infections, and no skeletal dysplasia except for 11 ribs bilaterally. Notably, pancreatic imaging showed reduced size and abnormal echogenicity without the typical fatty replacement (lipomatosis) seen in 82% of SDS patients in the North American registry. At 9 months of age, follow-up ultrasound showed a larger, more hyperechoic pancreas, suggesting that imaging findings evolve with age.
**Clinical Implications:** This case demonstrates that SDS can present in early infancy with isolated severe anemia requiring transfusion, without neutropenia, gastrointestinal symptoms, or skeletal abnormalities. Pancreatic imaging may show a small, abnormally echogenic pancreas without fat infiltration—findings that may be dismissed as inconsistent with SDS but likely reflect age-related changes. The only consistently present feature is laboratory evidence of exocrine pancreatic insufficiency (low fecal elastase), which should be investigated even when classic diagnostic criteria are not met. Clinicians should maintain a high index of suspicion for SDS in infants with low birth weight, poor postnatal growth, and unexplained hematological abnormalities, regardless of which cell lineage is affected. Early genetic testing for SBDS mutations is warranted in such cases to avoid diagnostic delay.