Severe Anemia and Neutropenia in a Patient with Gollop Wolfgang Syndrome: Implications of Malabsorption-Induced Micronutrient Deficiency. a Case Report

Introduction: Gollop-Wolfgang Complex syndrome is a rare congenital limb anomaly characterized by distal bifid femur and tibial agenesis. The etiology of this syndrome is unknown. Copper deficiency, an uncommon cause of severe anemia and cytopenia, results from malabsorption, issues with copper metabolism, or other nutritional deficiencies. Severe anemia and neutropenia due to copper deficiency have been documented in case reports and retrospective studies. Copper is vital for hematopoiesis, particularly in hemoglobin synthesis and red blood cell maturation. We present a case of Gollop-Wolfgang Complex presenting with severe copper deficiency.

Case Presentation: A 3-year-old female with Gollop-Wolfgang syndrome, spina bifida occulta, and a history of iron deficiency anemia who was being admitted for elective amputation of a bifid left femur presented with fatigue and chronic diarrhea. On admission, she exhibited significant anemia (Hb 2.3 g/dL), macrocytosis (MCV 100 fL), Neutropenia (500 K/µL), and an elevated Vitamin B12 (1,025 mcg). She was treated with blood transfusions and responded well. Comprehensive evaluation for viral infections, malabsorption, and inherited bone marrow failure syndromes was negative. Persistent severe anemia and neutropenia led to testing for micronutrient deficiencies, revealing undetectable copper, ceruloplasmin, and vitamin C, with normal zinc levels. Copper supplementation with IV Cupric Chloride improved anemia (Hb 9.5 g/dL), and neutrophil count (4,760 K/µL), and the patient became transfusion-independent. Genetic testing identified a homozygous variant of uncertain significance in the WDPCP gene associated with Bardet-Biedl Syndrome (BBS), though the patient's phenotype did not align with BBS.

Discussion: Gollop-Wolfgang syndrome, marked by tibial agenesis and bifurcated femur, has not been associated with hematologic abnormalities. Our patient had severe copper and vitamin C deficiency. Copper deficiency can lead to significant hematologic issues, including anemia and neutropenia. Our patient's chronic diarrhea suggested malabsorption despite normal endoscopic findings. Excessive cow's milk intake, known to interfere with copper absorption, was identified as a contributing factor. Copper deficiency should be considered in patients with unexplained severe anemia and neutropenia, especially when typical causes are ruled out.

Conclusion: Copper deficiency, though rare, should be evaluated in patients with severe anemia and neutropenia. Early recognition and supplementation can prevent severe hematologic complications. This case highlights the need for awareness and further research on copper deficiency, particularly in rare syndromes like Gollop-Wolfgang. A multidisciplinary approach is crucial for accurate diagnosis and management.

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