Infant with failure to thrive and hypotonia
The physical exam was remarkable for a quiet infant in no apparent distress. Her vital signs were normal, and her weight was 4.22 kg, putting her in the 0.04 percentile for age. Her head circumference and length were in the 50th and 30th percentiles, respectively. She preferred laying on her right side, and her head was elongated posteriorly with bilateral temporal flattening (dolichocephaly). She had hypoplastic labia minora and clitoris, and her skin was slightly mottled in the lower extremities without any areas of hypopigmentation. Neurologically, she was limp and had significant head lag, a poor grasp reflex, and sluggish movement of her extremities. She was admitted for further evaluation.
The patient had both failure to thrive (FTT) and hypotonia. Although each may occur independently, each also can adversely affect the other. It can be challenging to know how much testing will be required to determine the primary cause. However, approximately 70% of cases of FTT are nonorganic (psychosocial) and are without a medical etiology (Table 1).
Nonorganic factors of FTT
Inadequate intake is usually explained by neglect, errors in formula preparation, inappropriate food for age, or errors in feeding technique. Contributing factors to these problems include socioeconomic status, lack of proper instruction, or psychosocial concerns such as postpartum depression.1 Although the patient’s mother had an adequate supply of formula and was in the process of enrolling for the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), inadequate food intake is the most common nonorganic cause of FTT.
A thorough diet and social history are crucial as poverty and inadequate access to food are the greatest single risk factors for FTT in both developed and underdeveloped countries.1,2 A nutritional history may uncover improper formula preparation or use, infrequent feeding, or early/late transition to other liquids or solid foods and can be clues for insufficient caloric intake.2 It is well known that some families may dilute the formula to make it stretch to the end of the month or the next paycheck.
Although this patient’s hypotonia was the more significant part of her presentation, given her stable condition, the decision was made to do a trial of ad lib feeding with calorie count and monitoring strict intake and output before proceeding down the workup for organic etiologies. She was given unlimited access to the same formula and gained less than an ounce a day over the course of the week. As the week progressed, organic causes became more likely and further investigations were begun.
Organic factors of FTT
The remaining 30% of FTT cases are organic and can be explained by an underlying medical condition (Table 1). Organic causes are numerous and can be associated with almost any organ system. A thorough history and physical examination should direct the laboratory and radiologic testing, and newborn screening results should be reviewed.
For respiratory or gastrointestinal causes, coughing with feeding can be present. It can be a sign of poor swallowing, aspiration, or gastroesophageal reflux. Although the patient had neither symptom, she took a long time to finish her bottle, possibly signaling an organic cause. Gastrointestinal causes such as gastroesophageal reflux, diarrhea, or malabsorption can lead to FTT.1
Endocrine disorders such as hyperthyroidism and hypothyroidism lead to an increased metabolic demand and result in poor weight gain.3 The patient’s first and second newborn screening results, including thyroid tests, were normal. Chronic diseases or infections, malignancy, or autoimmune conditions lead to increased energy demands and also can present as FTT (sometimes termed “anorexia of chronic disease”).4
Metabolic disorders such as fatty acid disorders, amino acid disorders, and enzyme deficiencies can lead to inadequate absorption or utilization of nutrients.5 These disorders represent about 5% of cases of infantile FTT, and newborn state screening programs have been successful in detecting many of these errors.
Chromosomal disorders are also associated with FTT because structural deformities or systemic pathologies can prevent adequate intake.6 Clues for these organic causes of FTT include systemic disease, multiorgan involvement, and family history of congenital disorders.5,6 Although the patient’s family history was noncontributory, the presence of hypotonia and developmental delay prompted further evaluation.
The differential diagnosis of hypotonia is extensive. Generalized hypotonia and developmental delay are common signs of many neuromuscular diseases presenting in infancy. These may also include neurologic disease, endocrine and systemic metabolic diseases, and a number of syndromes, or they may be nonspecific neuromuscular expressions of malnutrition (ie, FTT) or chronic systemic illness (Table 27).