Coexistence of vitamin-D deficiency rickets and iron deficiency anemia has been described
in the past.[1] Occasionally, a more serious hematological condition, such as myelofibrosis, can
occur in association with vitamin-D deficiency. We present a toddler with rickets
due to vitamin-D deficiency and associated myelofibrosis which responded to oral cholecalciferol
therapy.
A 16-month-old girl presented with failure to thrive and progressive lower limb deformities
noticed since she was 6 months old. She was born of a nonconsanguineous union at term,
had a birth weight of 2.5 kg and was appropriately weaned. She had delayed motor development
and on enquiry, there was no past history of seizures, diarrhea, polyuria, jaundice,
or blood transfusions. She was a playful child who weighed 7 kg (−2.93 standard deviation
[SD]) with a length of 67 cm (−4.25 SD). Pallor, umbilical hernia, and features of
rickets along with anterolateral bowing of bilateral lower limbs and generalized hypotonia
were observed. Additionally, a soft hepatomegaly of 2 cm (span, 10 cm) and a firm
splenomegaly of 7 cm along the long axis was found; rest of the systemic examination
was unremarkable. The possible differential diagnoses considered were rickets in an
infant with a storage disorder or less likely a hematological neoplasm.
Blood and radiologic investigations confirmed vitamin-D deficiency rickets (serum
calcium: 8.4 mg/dL, serum phosphorus: 1.9 mg/dL, alkaline phosphatase: 1,136 IU/L,
25-hydroxy vitamin D: 11 ng/mL, and serum PTH: 104 pg/mL). Hemogram was suggestive
of hypochromic anemia and thrombocytopenia and peripheral smear revealed anisopoikilocytosis,
tear drop, and fragmented red blood cells with anemia and thrombocytopenia; reticulocyte
index was 1.2%. An abdominal sonography revealed moderate hepatosplenomegaly. A bone
marrow biopsy was advised; however, the family refused consent. Oral cholecalciferol
therapy at 3,000 IU/day was initiated along with oral calcium of 500 mg/day. Iron
syrup was advised at 6 mg/kg/day. On follow-up, the child showed remarkable clinical
improvement in the form of gaining motor milestones and a significant reduction in
organomegaly. At 2 months, the liver was no longer palpable and the spleen had reduced
to 3-cm clinically. This was concurrent with a biochemical improvement in hemoglobin,
platelets, phosphorus, and alkaline phosphatase levels.
The differential diagnosis in an infant with splenohepatomegaly, rickets, and bicytopenia
included a hematological neoplasm, such as leukemia, a storage disorder, such as Gaucher's
disease, as well as hyperparathyroidism-induced myelofibrosis. In an otherwise healthy
baby without lymphadenopathy or atypical lymphocytes on peripheral smear and normal
serum lactate dehydrogenase levels, a diagnosis of hematological neoplasm was unlikely.
Likewise, absence of consanguinity, cherry red spot on fundus examination, as well
as typical radiological features, such as Erlenmeyer's flask deformity, went against
the diagnosis of a storage disorder. Reduced blood cell counts along with leucoerythroblastosis
on peripheral smear are corroborative for the diagnosis of myelofibrosis and requires
a histological confirmation. Characteristically, a bone marrow aspiration results
in a dry tap with biopsy demonstrating hypocellular bone marrow with increased reticulin
deposition. Although, in our child, a bone marrow biopsy could not be performed, the
presence of vitamin-D deficiency, characteristic peripheral blood picture, normal
reticulocyte index, and the rapid improvement of bicytopenia and organomegaly on oral
cholecalciferol therapy favored the diagnosis of vitamin-D deficiency–associated myelofibrosis.
In the pediatric population, myelofibrosis commonly occurs secondary to neoplasms,
such as leukemia and lymphoma, or to nonneoplastic conditions, such as vitamin-D deficiency,
systemic lupus erythematosus, Fanconi's anemia, and hyperparathyroidism; primary myelofibrosis
is rare.[2] Children with myelofibrosis associated with vitamin-D deficiency typically present
in infancy. Hyperparathyroidism resulting from vitamin-D deficiency is postulated
to be responsible for the myelofibrosis.[3] Increased parathormone levels lead to decreased erythropoietin receptors on erythroid
progenitor cells and increased medullary fibrosis. The hepatosplenomegaly results
from subsequent extramedullary hematopoiesis. Another possible pathophysiologic feature
of vitamin-D deficiency induced myelofibrosis could involve reduced levels of active
vitamin-D metabolites which are responsible for the maturation of the monocyte and
megakaryocyte precursors leading to reduced degradation and increased deposition of
collagen.[4] Along with cellular differentiation, vitamin D also plays a role in cellular proliferation;
children with vitamin D–induced myelofibrosis have lower concentrations of CD34+ cells
in bone marrow but increased levels in peripheral blood and splenic aspirates both
of which return to normal with treatment of rickets.[5]
Previous published case reports mainly showed a partial or complete improvement of
clinical, radiological, and hematologic parameters with vitamin-D therapy, irrespective
of the regimen used.[6] However, persistent pancytopenia and death due to septic shock have also been reported.[2]
Vitamin-D supplementation up to 1 year of age is routinely recommended. Also, secondary
myelofibrosis must be kept in mind for any child presenting with rickets and hepatosplenomegaly.
A high index of suspicion can obviate the need for extensive workup and support a
more conservative approach toward management.
