Being on call for the hospital's pediatric general medicine and infectious disease services has kept you busy this morning, admitting children with dehydration from gastroenteritis and initiating sepsis work-ups for febrile infants. And once again, your pager displays the emergency department number.
In the ED, the team reports that your next admission is a 6-month-old boy who has been vomiting. His name seems familiar.... That's it! About a month ago, you heard your colleagues discussing this child's case during an earlier admission—they were describing him as one who hadn't fared well in the game of "formula roulette." You don't know the details of how the formula had been changed, but you do remember that he was admitted then with vomiting, hyponatremia, and failure to thrive.
You look at the chart for background and one notation is prominent: A diet history that was taken at the prior visit to the ED a month ago revealed that the first-time parents, having grown frustrated with their baby's persistent vomiting, decided to feed him with their own formula of 1:1 cow's milk and water. A few days afterward, he was admitted, rehydrated with intravenous fluids, and started on commercial ready-to-feed, iron-fortified, milk-based infant formula. The vomiting ceased by the third day after admission and the sodium level improved by discharge. His parents were given explicit instructions not to dilute the premixed formula.
As you walk into the examining room, the young mother is playing with your babbling patient, who is nearly sitting independently (tripoding) and who appears to be the size of, roughly, a 2-month-old. The mother appears tired and is hunting through two of her bags for the baby's favorite toy; one bag appears to be a backpack containing heavy textbooks and the other is full of baby supplies, including the ready-to-feed formula.
When, you ask, did the vomiting begin? And what has been done so far to try to stop it? The mother explains that the baby has been seen at several different clinics—at first because of health insurance problems, later because she and her husband saw no improvement in his vomiting and poor growth. The vomiting began at about 3 months of age, while the baby was being breastfed; various physicians noted that he was "growing slowly." The vomiting is always postprandial, she explains, involves food only, and is never forceful. It is also nonbilious and nonbloody. The child's pediatrician encouraged the mother to continue breastfeeding because there was no blood in the stool to support a milk-protein allergy.
At-home empiric trials of ranitidine (Zantac) and metoclopramide (Reglan) were started for gastroesophageal reflux. The baby continued to vomit and was unable to keep down the medications. The parents decided to try a standard milk-based infant formula—in fact, they tried several brands. They returned to the clinic for the 4-month well-child visit with the baby still experiencing postprandial emesis and having poor weight gain.
Formula for trouble?
But the infant seemed to vomit even more when given a milk-based formula than when breastfed, so the pediatrician again entertained the idea of milk-protein allergy and switched the diet to, first, a soy-based formula and then to a protein hydrolysate-based formula. Plans were made for an outpatient upper gastrointestinal radiographic series and abdominal ultrasonography (US) to evaluate for reflux and anatomic abnormalities.
Because vomiting persisted even with hydrolysate-based formula, the parents decided, on the recommendation of a family member, to try the ill-advised diluted cow's milk diet you read about earlier. A few days before the scheduled radiographic studies, the infant began vomiting after every meal and was taken to the ED. He had by then been taking the diluted cow's milk for five days.
Once the baby was rehydrated and discharged, according to his mother, the vomiting restarted intermittently after about one week, and had become much worse in the past two days. She asserts that she has given him ready-to-feed formula only, three or four ounces every four hours, as well as homemade pureed baby food. She also comments that he seems more interested in eating food if it is salty, and that he tends to vomit less when table salt is added to each mouthful!
Now, fill in the blanks!
You file that curious observation away for a moment and proceed with a review of systems, which is otherwise negative except for a mild case of apparent atopic dermatitis that is not being treated. The patient has not had diarrhea or constipation. The usual stool pattern is one soft stool every one or two days since he has been given formula—as opposed to five or six stools a day when he was breastfed. He has not had fever, prior infection, polyuria, or polydipsia.
The birth history is unremarkable. The baby was born at term by uncomplicated vaginal delivery. He was born in Ohio, where standard newborn screening includes a test for congenital adrenal hyperplasia; all tests on the screen were negative.
The patient is not taking any medications at the moment. The only medications he has been given include occasional acetaminophen and the brief trials of ranitidine and metoclopramide. Immunizations are up to date.
The family history is unremarkable, and specifically negative for childhood deaths, congenital anomalies, failure to thrive, and cardiac, thyroid, adrenal, and renal disease. He is the first child of a young married couple from Macedonia. The parents deny consanguinity. They are graduate students who plan to return to Macedonia after graduation in the next few months.
On physical exam, the baby is alert, afebrile, and interactive and appears developmentally appropriate for the age of 6 or 7 months. He is, however, very small for his age. He is also hypertensive (blood pressure, 118/78 mm Hg). Heart rate is 146/min; respiratory rate, 30/min. Weight is 5.3 kg (well below the third percentile); he has gained only 240 g since discharge one month ago. Length is 63.5 cm (also at the third percentile) and head circumference is at the 25th percentile. The head is normocephalic, with a soft, open anterior fontanel.
The pupils are equally round and reactive to light, with no eye abnormalities. Mucous membranes are moist without lesions. The neck is supple without palpable masses. The chest is clear to auscultation. The heart rhythm is regular, with normal heart sounds and without murmur. The abdomen is soft without organomegaly. The genital exam reveals a normal Tanner stage-I male with bilaterally descended testes and normal penile length. The neurologic exam reveals normal tone and no focal findings. Skin is without hyperpigmentation.
A basic metabolic profile that was ordered on arrival in the ED is significant for a sodium level of 126 mmol/L; potassium (non-hemolyzed), 6.2 mmol/L; chloride, 91 mmol/L; and mild metabolic acidosis .
A differential diagnosis as wide and as deep as the sea
You pause to summarize what you've seen so far. Here is a 6-month-old male with several significant findings:
* persistent vomiting
* failure to thrive even with appropriate feeding
* recurrence of hyponatremia
* mild hyperkalemia
* hypochloremia
* hypertension.
Also notable is that the child appears euvolemic on physical examination.
The differential diagnosis of hyponatremia and failure to thrive with vomiting is extensive. Common causes include incorrect preparation or dilution of formula and vomiting brought on by gastroesophageal reflux, pyloric stenosis, difficulty swallowing, intestinal malrotation with obstruction, and central nervous system lesions characterized by elevated intracranial pressure.
Even though the parents have not reported a history of diarrhea, your exhaustive initial differential includes diarrheal diseases that lead to hyponatremia and failure to thrive. These include infection (viral, bacterial, and parasitic) and malabsorption from cystic fibrosis, celiac disease, and a congenital deficiency of any of several enzymes involved in the digestion of carbohydrates and proteins.
Less common causes of hyponatremia and failure to thrive include chronic liver disease (including glycogen storage disorders) and endocrine disorders such as hypothyroidism, diabetes mellitus (with pseudohyponatremia), and glucocorticoid or mineralocorticoid deficiency. In addition to adrenal hormone deficiencies, other renal salt-wasting conditions include nephritis, cystic disease, obstructive uropathy, use of a diuretic, renal tubular acidosis, and the syndrome of inappropriate antidiuretic hormone secretion (associated with tuberculosis, hypothyroidism, lung and CNS processes, and use of various medications).