A mummy emerges from the grave: Scurvy confounding the clinical presentation of a child with Fanconi anemia
Authors: Alper Ozcan, Sibel Saracoglu, Jeffrey M. Verboon, Musa Karakukcu, Turkan Patiroglu, Abdulhakim Coskun, Vijay G. Sankaran, Ekrem Unal
Journal: American Journal of Hematology (2019)

A 10-year-old Syrian refugee girl was referred to Erciyes University for hematopoietic stem cell transplantation (HSCT) for Fanconi anemia (FA) associated aplastic anemia with platelet transfusion refractoriness. Her parents were first cousins and one of her siblings had previously died due to FA. On admission, her body weight was 23 kg (50 P), height was 124 cm (<3P), and head circumference was 47.5 cm (10P). Her physical examination revealed petechiae, purpura, and hyperpigmented lesions on the trunk and extremities. Blood count analyses revealed a hemoglobin of 6.3 g/dL, mean corpuscular volume of 103 fL, leukocyte count of 810 × 109/L, and platelet count of 2 × 109/L. Bone marrow aspiration and biopsy showed hypoplastic marrow with 10% cellularity without dysplasia. A chromosomal breakage test with diepoxybutane was consistent with FA. Using whole exome sequencing, we identified a rare, predicted pathogenic missense variant (M-CAP score: 0.16; FANCA: p.Gly1009Asp), which was found in the heterozygous state in both parents. Importantly, using whole exome sequence coverage to infer copy number, we identified a homozygous deletion spanning exons 18-28 in the patient, which was heterozygous in both parents and absent from the exomes of 274 unrelated, control exomes.1 As she had no HLA matched donor, we planned to perform T-cell receptor alpha beta depleted haploidentical HSCT from her mother. During the follow up period before the HSCT, she had severe pain in her extremities of unclear etiology concerning for an FA-associated malignancy or other complication. Pre-contrast and post-contrast MR images demonstrated bone marrow enhancement. MRI of whole body and coronal short tau inversion recovery (STIR) images demonstrated symmetrical, heterogeneous hyperintense signal changes in bone marrow at humeral proximal epiphyseal, femoral distal metaphyseal, and tibial proximal metaphyseal. T1-weighted coronal knee image shows hypointense signal changes in the bone marrow (1). According to the clinical features, laboratory findings, and genetic analysis she had FA, but MRI revealed that she may also have scurvy. The serum vitamin C/ascorbate levels were very low (0.1 mg/dL, normal ranges: 0.6-2 mg/dL). She was diagnosed with FA complicated by scurvy. Vitamin C supplementation was provided, after which the pain disappeared within 1 week. The patient subsequently underwent HSCT. Although neutrophil and full chimerism was achieved at the +10 day she died because of grade III skin, and gastrointestinal graft-vs-host disease at +23rd day. FAA is an inherited disease characterized by bone marrow failure, short stature, skeletal abnormalities, and a high relative risk of myeloid, and epithelial malignancies due to genomic instability. Scurvy is a rare disorder that can be seen in patients with severely restricted diets due to ascorbate deficiency.2 The features of scurvy can confound a diagnosis of another genetic blood disorder, such as FA. It may be speculated that the scurvy should complicate the clinical course by worsening the pancytopenia and indeed recent work suggests that ascorbate may have a critical role in regulating hematopoietic stem cell function, as does the FA pathway.3 Hematologists managing patients originating from low income countries should consider factors that may confound various blood diseases such as FA. Nutritional deficiencies can be a significant contributor to such complicated presentations.