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A 13-month-old boy has reached a plateau in weight gain, even as his length and head circumference maintained their relative position on growth charts. His diet shows no abnormalities.
GEORGE K. SIBERRY, MD, MPH, SECTION EDITOR
|Jump to:||Choose article section... If, at first, you don't succeed. . . . . . try, try again The die is cast "Although I laugh and I act like a clown . . ." The appearance of the diencephalic syndrome ". . . beneath this mask I am wearing a frown"|
The mother of a 13-month-old boy has brought him to your clinic in frustration over his poor weight gain and her sense that "something is wrong with him." His primary care pediatrician had followed him regularly from 4 to 7 months of age for severe constipation; on a diet of breast milk and elemental formula the infant had been passing stool only once every five to seven days. At the time, a diagnosis of Hirschsprung disease was entertained, but further work-up was suspended when he responded to treatment with polyethylene glycol. At 7 months of age, the boy's weight was 6.9 kg (10th percentile) and his length was 67.1 cm (25th percentile), and he was passing stool every other day.
Over the past four months, however, his weight has reached a plateau, even as his length and head circumference maintained their relative position on growth charts. His mother reports that he continues to have formed, soft, nonbloody bowel movements five to seven times a week without the aid of medication. She denies vomiting, fever, rash, recent or recurrent infection, oral ulcers, snoring, mouth breathing, or sweating upon feeding. Urine output is normal, she reports, with four or five wet diapers a day. He walked at 11 months of age; speaks three words; has no vision, hearing, or coordination problems; and is otherwise developmentally appropriate.
You review his diet in detail but discover no significant abnormalities: He still breastfeeds occasionally at night, eats a varied diet, and continues to drink an elemental formula. He may have had some loose stools after eating watermelon, his mother recalls, but otherwise has not had difficulty tolerating any particular foods, including wheat products. The only notable problems, she claims, are that he is so active that he has to be distracted to eat and that he does not take in a large amount of food at a meal.
The infant's birth history is unremarkable. Birth weight was 3.1 kg (25th percentile) and length, 48.5 cm (25th percentile). Immunizations are current and he has no allergies to medication. He is not in day care and has not traveled out of the area. A 6-year-old sister is healthy and thriving. The family history is notable for a maternal uncle with an "allergy" to wheat products and a paternal aunt who grew poorly as a child but is now "normal." His mother denies risk factors for human immunodeficiency virus infection.
On physical examination, the infant appears extremely thin but alert and well. His weight is now 7.1 kg (well below the 5th percentile); length, 74 cm (25th percentile); and head circumference, 45.5 cm (25th percentile). Heart rate is 120/min; respiratory rate, 30/min; and blood pressure, 94/54 mm Hg. The anterior fontanel is closed. Pupils are equal, round, and reactive to light, and extraocular movements are intact. The oropharynx is clear, the neck is supple without lymphadenopathy or thyromegaly, and the heart is regular without murmurs. The lungs are clear and the abdomen is soft, nontender, and nondistended. No hepatosplenomegaly or masses are palpated. Rectal tone is normal. Examination of the skin reveals subcutaneous tissue wasting but no rash. Deep-tendon reflexes are normal and symmetric, and he appears to use all his muscles well as he races about the room, babbling happily.
The evaluation of failure to thrive in an infant is often difficult because the differential diagnosis is broad. It often helps to remember that, ultimately, insufficient growth has only three possible causes1:
Nothing about your encounter with this infant and his mother suggests that neglect is a factor in his poor growth. She is clearly concerned about her son and the two appear appropriately bonded. Nevertheless, you keep this possibility in mind and remember that, when psychosocial failure to thrive is being considered, the appropriate step is to hospitalize the child and carefully monitor his intake of calories and parent-child interactions during feeding.
What about his caloric intake? His mother, well informed by the primary care pediatrician, has brought you a three-day food diary. The clinic's nutritionist reviews the diary andeureka!informs you that the infant is, indeed, consuming only 70 to 80 kcal/kg/d (average for a normal, healthy infant, 100 kcal/kg/d).
But not so fast: Why is he not taking in enough calories? His mother claims that it is a problem of hyperactivity, but you hesitate to place all the blame on that "diagnosis." Despite the absence of vomiting in his history, could this boy be suffering from gastroesophageal reflux disease (GERD) and, therefore, refusing food? GERD would certainly be one of the most likely diagnoses in a child this age. And what about the vague family history of an "allergy" to wheatcould he be suffering from celiac disease? Most people with gluten-sensitive enteropathy have diarrhea as a presenting complaint, but it's well known that failure to thrive is sometimes the only manifestation.
You decide that his degree of malnutrition is severe enough to warrant hospitalization for further evaluation. You begin with screening laboratory tests, and find that the complete blood count, erythrocyte sedimentation rate, and chemistry panel are entirely normal. A celiac paneltests of antiendomysial and antigliadin antibodies is negative. Stool is negative for blood, fat, reducing substances, ova, and parasites. The nursing staff reports that Mom is an excellent caregiver and confirms that the child limits his intake to approximately 75 kcal/kg/d.
You decide to proceed with upper- tract endoscopy, which reveals mild esophagitis and gastritis that are consistent with GERD; biopsies of stomach and duodenum are otherwise normal. You move to begin therapy with a proton-pump inhibitor, but his parents decide against a prokinetic agent once they are informed of possible side effects.
Despite making the diagnosis of GERD, concern nevertheless lingers in your mind. Simply put, you feel that you are still missing something. This child just seems too happy for reflux pain to be the sole explanation for his lack of adequate caloric intake.
Could the boy's gastrointestinal findings be a red herring? Back you go, then, to consider other causes of failure to thrive. You decide to check the results of a few more tests while waiting to see whether his appetite improves on an acid-blocking medication.
Chronic renal failure? Ruled out by normal blood urea nitrogen and creatinine levels. Renal tubular acidosis? Seems improbable with a normal serum bicarbonate level, but you decide on urinalysis anyhow. Results are normal. Cystic fibrosis? Unlikely, given the normal stool studies, but you order a sweat chloride test, just in case. It, too, returns normal. What about congestive heart failure? Doubtful, based on your physical examination, so you decide against further cardiac tests. And an immune deficiency state seems unlikely based on your initial history and examination and the lab results.
What about an endocrinologic or metabolic problem? Nothing obvious strikes you; he is bright and active. But, to be safe, you check thyroxine, cortisol, lactate, and pyruvate levels. They, too (of course), are normal. You decide against a test of growth hormone because his length has been preserved.
Yet during all this investigation, the boy continuesto your dismayto eat poorly and not gain weight. You, and his parents, are more and more concerned and frustrated. Despite the potential for creating oral aversion, you then recommend a trial of nasogastric tube feeding. But the parents want to go home and think it over.
While Mom and Dad consider what to do next, a new player enters the scene. Nine days after your initial evaluation, and after they observe that the boy has seemed unsteady for two days and has fallen several times, they bring him to the emergency room. There, ataxia and anisocoria are noted. The treating physicians, concerned about the possibility of an intracranial bleed, order an emergent noncontrasted computed tomographic (CT) scan of the head.
Results are surprising: No intracranial bleed but a 3.5 x 3 x 3 cm, homogenously hypodense tumor visualized in the suprasellar region. There is no hydrocephalus. The infant is taken for magnetic resonance imaging (MRI), which reveals a hypointense mass on T1-weighted images that enhances brightly with gadolinium contrast. T2-weighted images confirm tracking posteriorly along the optic tracts. These findings are interpreted as a chiasmatic pilocytic astrocytoma.
The pieces of the puzzle start to fall into place. Although malignancy should always be considered in the differential diagnosis of failure to thrive, it is an extremely rare cause. A brain tumor is even less likely in the absence of localizing signs, which this patient did not have.
Or did he?
Looking back on the initial presentation and evaluation, you realize that the fact that he was such a happy and active child while suffering from cachexia is a localizing sign of its own. This constellation of symptoms is classic in the diencephalic syndrome.
The diencephalon is the basal portion of the embryonic prosencephalon, from which the hypothalamus, thalamus, and pineal glands derived. The diencephalic syndrome is characterized by a number of clinical features (see the table). Emaciation often occurs despite adequate energy intake, and linear growth is preserved. The syndrome occurs almost exclusively in infants and young children, most often as the result of a slow-growing, low-grade glioma in the diencephalic structures. The precise endocrine mechanism of the diencephalic syndrome has never been determined.2,3
The differential diagnosis of a tumor in this region includes hypothalamic glioma, craniopharyngioma, germ cell tumor and teratoma (ectopic pinealomas), and hamartoma of the tuber cinereum. A glioma of the optic chiasm that compresses the hypothalamus may also cause diencephalic syndrome. MRI is usually able to distinguish among these tumors, although tests of the levels of a-fetoprotein and b-human chorionic gonadotropin are recommended to rule out a germ cell tumor. Biopsy is rarely indicated.
A pilocytic astrocytoma is considered a low-grade glioma; prognosis is excellent. Regrettably, the location of a chiasmatic or diencephalic tumor makes gross total resection extremely difficult, and postoperative morbidity (hemiparesis or visual field defects) may occur in as many as 75% of patients treated surgically. Because of the morbidity associated with radiotherapy in a young infant (that is, endocrinologic and intellectual dysfunction), chemotherapy is the treatment of choice. The usual regimen consists of carboplatin and vincristine. Even without resection, the 10-year-survival is approximately 70% to 80%. One other fact to keep in mind: the association between glioma and neurofibromatosis, seen in as many as 20% of patients who have this tumor.
On admission to the ER, our patient truly seemed to be suffering from ataxiaan uncommon finding with a chiasmatic or diencephalic tumor, which instead presents more often with either visual field defects, caused when the tumor obstructs cerebrospinal fluid pathways from the third ventricle and resulting in hydrocephalus or a neuroendocrine abnormality (for example, precocious puberty and diabetes insipidus).
"In the field of observation," Louis Pasteur said, "chance favors the prepared mind." This child was fortunate that the ER physicians were lucky enough to find an additional clue that led to the correct diagnosis before his disease progressed. Now, should chance ever lead a child with the diencephalic syndrome across your path, your mind will be prepared to make the diagnosis.
1. Bauchner H: Failure to thrive, in Behrman RE, Kliegman RM, Arvin AM (ed)s: Nelson's Textbook of Pediatrics, ed 15. Philadelphia, Pa., WB Saunders, 1996, pp 122,123
2. Fenichel GM: Disorders of the visual system, in Clinical Pediatric Neurology, ed 3. Philadelphia, Pa., WB Saunders; 1997, p 338
3. Heideman RL, Packer RJ, Albright LA, et al: Tumors of the central nervous system, in Pizzo PA, Poplack DG (ed): Principles and Practice of Pediatric Oncology, ed 3. Philadelphia, Pa., Lippincott-Raven, 1997, pp 633697
George Siberry, ed. Christopher Dvorak. A 13-month-old fails to thrive: Playing those mind games. Contemporary Pediatrics 2002;9:27.