Readers note inconsistencies in Puzzler case

Regarding “Choking and cyanosis in an infant with sickle cell disease,” by Taylor M. Triolo, MD, and L. Barry Seltz, MD, Puzzler, Contemporary Pediatrics, February 2015:

Good discussion of [an apparent life-threatening event], including the fact that you need to consider electrolyte abnormalities as causative factors. However, there are a few inconsistencies worth noting.

First, anemia at 2 months of age in patients with [sickle cell disease (SCD)] is not due to SCD, as the [red blood cells] present still contain primarily fetal hemoglobin. Likewise, the [mean corpuscular volume] of 90 has nothing to do with SCD. If the patient were older (4 to 6 months or more), then SCD might play a role. Also, while the mild elevation of [parathyroid hormone (PTH)] may indicate inadequate response to hypocalcemia by the parathyroid glands, the diagnosis of hypoparathyroidism due to 22q del is suspect.

Even only mildly elevated PTH should produce hypophosphatemia, but this patient is hyperphosphatemic, suggesting end-organ resistance to PTH (pseudohypoparathyroidism), and not hypoparathyroidism alone.

M. Verive, MD 

Posted online

Great case, very informative, but I agree with Dr. Verive. The high PTH level indicates pseudohypoparathyroidism.

Lotfi Bashir, MD

Posted online

Drs. Triolo and Seltz respond:

We thank Drs. Bashir and Verive for their comments. We agree that anemia in our patient was unlikely to be due to SCD prior to 4 months of age. The etiology of our patient’s hypocalcemia was complex and likely multifactorial. Our patient had severe neonatal vitamin D deficiency. Yet it was surprising how minimally elevated our patient’s PTH response was in the setting of such significant hypocalcemia and vitamin D deficiency. 

Vitamin D deficiency typically results in low serum phosphorus due to secondary hyperparathyroidism and phosphaturia. However, in neonates vitamin D deficiency has occurred with elevated serum phosphorus and normal to only slightly elevated PTH levels (Thomas TC, et al. Pediatrics. 2012;129(6):e1461-e1467). We considered delayed maturation of the parathyroid hormone axis and agree that pseudohypoparathyroidism remains a possibility. 

As our patient had congenital heart disease, [fluorescence in situ hybridization] testing for 22q11.2 deletion syndrome was sent, and its positive result suggested a combination of severe vitamin D deficiency and 22q11.2 deletion syndrome as the cause of our patient’s hypocalcemia.  

Taylor M Triolo, MD

L Barry Seltz, MD