Year : 2010 | Volume
: 21 | Issue : 3 | Page : 511--514
Congenital vitamin D deficiency: A rare etiology of an acute life threatening event in early infancy
Rafat Mosalli1, Elsayed Yasser2, Abbass Mohammad Ali2, Saleh Al Harbi1,
1 Department of Pediatrics, Medical College Umm Al-Qura University, Makkah, Saudi Arabia
2 Department of Pediatrics, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia
Department of Pediatrics, Umm Al-Qura University, P.O. Box 7607, Makkah
Infants born to mothers with deficiency of vitamin D and/or calcium due to cultural modifications in their diets, life style and clothing habits, are at risk of developing early and fatal sequelae of hypocalcemic vitamin D deficiency. We present a 44-day-old infant with hypocalcemia secondary to congenital vitamin D deficiency, who presented as a recurrent Acute Life Threatening Event (ALTE) resulting in an unexpectedly prolonged intensive care course. This report suggests that evaluation of vitamin D status should be included as part of the workup of ALTE and we describe evidence-based preventive measures for both mothers and infants who are at risk for vitamin D deficiency.
|How to cite this article:|
Mosalli R, Yasser E, Ali AM, Harbi SA. Congenital vitamin D deficiency: A rare etiology of an acute life threatening event in early infancy.Saudi J Kidney Dis Transpl 2010;21:511-514
|How to cite this URL:|
Mosalli R, Yasser E, Ali AM, Harbi SA. Congenital vitamin D deficiency: A rare etiology of an acute life threatening event in early infancy. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Aug 11 ];21:511-514
Available from: http://www.sjkdt.org/text.asp?2010/21/3/511/62692
Reports of vitamin D deficiency as a major health problem in the Middle East and in Saudi Arabia are not new. , Seizures due to hypocalcemic, vitamin D deficiency in early infancy have been documented in the literature,  but early occurrence in association with recurrent Acute Life Threatening Events (ALTEs) has been rarely reported. We describe a successfully treated infant who presented to our pediatric emergency unit with recurrent ALTEs secondary to severe hypocalcemia due to low maternal and infant vitamin D levels, and briefly outline preventive strategies for a high-risk population.
A 44-day-old full-term male infant presented to the emergency room with repetitive brief attacks of apnea, generalized hypotonia, cyanotic spells, and focal right sided seizures of one day's duration. There was no history of fever, he had no dysmorphic features and both his physical and neurological examination was unremarkable.
The pregnancy was normal and the baby was born at term by an uncomplicated cesarean section because of a previous cesarean section. His birth weight was 4.2 kg (75th-95th percentile), head circumference was 34 cm. He was exclusively breast-fed from birth. Both parents are Saudi in origin; the mother is 30-years-old and always dressed in cultural Saudi garments, where most of her body was covered. The mother did not receive any vitamin or calcium supplements during the pregnancy. She is a house wife, who smoked and her lifestyle did not involve any physical exercise. Her diet consisted preferentially of junk food without daily vitamins and similarly, her infant did not receive any vitamins.
In the emergency room, the baby had repetitive similar attacks of apnea and focal seizure, lasting between a few seconds to one minute that needed multiple doses of intravenous diazepam, without complete recovery. His biochemistry was significant for a low calcium level of 4.2 mg/dL (reference range: 8.7-10 mg/dL). Hence, he was admitted to the pediatric intensive care unit (PICU) for uncontrolled apnea and cyanotic spells which required further multiple intravenous calcium gluconate boluses and anti-seizure medications including diazepam and phenobarbital. His seizures and apnea spells ceased fully, 48-hours after starting treatment.
Hypocalcemic vitamin D deficiency in this infant was subsequently diagnosed on the basis of a low serum calcium level of 4.2 mg/dL, (reference range: 8.7-10 mg/dL) extremely low level of 25-hydroxy vitamin D level of 7 nmol/L (reference level > 50 nmol/L), elevated parathyroid hormone level (PTH) of 351 pg/mL (reference range: 8-51 pg/mL), with normal 1,25-hydroxy vitamin D level of 84 pmol/L (39 pmol/L-193 pmol/L) and normal phosphate of 2 mmol/L (1.25-2.10 mmol/L).
A low 25-hydroxy vitamin D level indicates that vitamin D stores are low, while a normal 1,25-hydroxy vitamin D level confirms that the child is able to convert vitamin D to its active form. The infant's PTH level was appropriately elevated at 351 pg/mL (normal ≤ 3 pg/ mlL. All other laboratory investigations including serum magnesium, electrolytes, glucose, urine calcium and 24-hour calcium excretion, liver function tests, urea and electrolytes, Creactive protein, lactate, lumbar puncture and blood culture were normal. There was no clinical or radiological evidence of rickets. The CT scan of the brain and electroencephalography (EEG) were normal.
Maternal investigations demonstrated a total calcium level of 5.2 mg/dL (reference range: 8.7-10 mg/dL), low 25-hydroxy vitamin D level of 10 nmol/L (optimal 75 nmol/L to 225 nmol/L) and an elevated PTH level of 130 ng/ L (normal 10 ng/L to 65 ng/L), confirming the diag-nosis of vitamin D deficiency in the mother as well.
In the PICU, the infant needed high doses of both intravenous calcium therapy and alphacalcidol (650 ng/kg) i.e. six times the normal dose of 100 ng/kg. After nine days, the patient was transferred to the general ward, where he continuously required oral calcium supplements (2.5 gm/day in divided doses) which was weaned gradually over one week of discharge in conjunction with a weaning regimen of alphacalcidol. Drug doses were titrated according to the follow-up investigations of serum calcium and 25-hydroxy vitamin D. One month after discharge, the baby was switched over to vitamin D 3 drops at a maintenance dose of 400 IU/day, and continued to maintain normal calcium and total 25-hydroxy vitamin D levels. He had no further clinical episodes and his developmental milestones were consistent with his chronological age.
Vitamin D deficiency remains a major public health problem in the Middle East especially among infants who are exclusively breastfed and born to mothers with high risk factors such as low vitamin D stores, dark skinned, wearing traditional garments and/or living a sedentary lifestyle which further limit adequate ultraviolet light exposure. ,,
Evidence suggests that adequate maternal vitamin D status during pregnancy and lactation are not only important for an infant's growth and skeletal development, but may also influence the health status of the child later in life. These findings have modified our knowledge and understanding of vitamin D metabolism, and our recommendations for supplementation.
An Apparent Life Threatening Event (ALTE) is not uncommon emergency problem that constitutes approximately 0.6-0.8% of all emergency visits of infants.  It is defined as ''an episode that is frightening to the observer and is characterized by some combination of apnea, color change (usually cyanotic or pallid), marked change in muscle and choking".  It often presents as a diagnostic dilemma and management challenge as resuscitation may be necessary. 
ALTE due to hypocalcemia is a rare cause, which constitutes less than 2% of all cases. , Hence the work-up after a first unexplained ALTE should include obtaining electrolytes, including calcium. Once hypocalcemia is identified, further investigations should define vitamin D status for both infant and mother.
In a recent study in Saudi Arabia,  hypocalcemic seizures were the most common clinical presentation of vitamin D deficiency (84%) significantly higher than 50% reported in the western literature. Hypocalcemic seizures due to vitamin D deficiency should be treated with calcium, in combination with vitamin D replacement therapy.
Our case had all the known risk factors of vitamin D deficiency. In addition, it appears that neonatal ALTE, although a rare event, constitutes a serious presentation of vitamin D deficiency which required prolonged ICU stay and involved high direct hospital costs. It can be argued that this complication is preventable if both mothers and infants have adequate vitamin D stores and proper supplementation.
Recently, both the American Academy of Pediatrics (AAP) and the Canadian Pediatric Society (CPS) , have revised the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D beginning in the first two months after birth to a minimum daily intake of 400 IU beginning soon after birth, especially for infants whose mothers are vitamin D deficient or in those infants not exposed to adequate sunlight. Supplementation should be continued unless the infant is weaned to at least one liter/day of vitamin D-fortified formula. In addition, relatively high-dose maternal vitamin D supplements (2000 IU/day), together with maintaining a healthy, balanced diet is needed.
This new guideline should be emphasized as part of the educational program of all pregnant and lactating mothers, especially those who are at risk for vitamin D deficiency.
In summary, this case illustrates that the evaluation of vitamin D status should be included as part of the work-up of ALTE in infants especially if they present to the pediatrician with symptomatic hypocalcemic seizures. This report adds to the already existing evidence that vitamin D deficiency remains a major health problem in Saudi infants, especially for mothers who already have low vitamin D stores due to cultural, nutritional, or health style risk factors. We hope that our recommendation will be supported by vigorous measures to improve the vitamin D intake of Saudi mothers and infants. This should include formal public health campaigns increasing awareness about the importance of maternal and infant vitamin D supplementation and educating women to change their life style and attitude towards sun exposure.
The authors express their gratitude to Dr. Bosco Paes for his valuable editorial comments of this report
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