Christopher C. Dvorak

GEORGE K. SIBERRY, MD, MPH, SECTION EDITOR

 A 13-month-old fails to thrive: 
  Playing those mind games 

 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 causes

 caregivers' failure to offer sufficient calories 

 the child's failure to take in sufficient calories 

 the child's failure to retain sufficient calories. 

 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 andeureka!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 wheatcould   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 paneltests 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 continuesto your dismayto   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. 

 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. 

 "Although I laugh and I act like a clown . . ." 

 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.

The appearance of the diencephalic syndrome

 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. 

 ". . . beneath this mask I am wearing a frown" 

 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 ataxiaan   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: 

 ed 15. Philadelphia,   Pa., WB Saunders, 1996, pp 122,123 

 2. Fenichel GM: Disorders of the visual system, in 

 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 633697 

 DR. DVORAK is a fellow in pediatric hematology/ oncology at Lucile Packard   Children's Hospital at Stanford University Medical Center, Palo Alto, Calif. 

 DR. SIBERRY is a fellow in pediatric infectious disease at The Johns Hopkins   Hospital, Baltimore, Md. 

 

George Siberry, ed. Christopher Dvorak. A 13-month-old fails to thrive: Playing those mind games. 

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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.

Christopher C. Dvorak

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Pediatric Puzzler: A 13-month-old fails to thrive: Playing those mind games