Table 1.
Clinical findings in this study.
| Family 1 | Family 2 | Family 3 | ||||
|---|---|---|---|---|---|---|
| Patient 1 | Patient 2 | Patient 1 | Patient 2 | Patient 3 | Patient 1 | |
| Parental consanguinity | + | + | + | + | + | - |
| Pregnancy and gestational age | Preeclampsia 34 weeks |
Born at term | Born at term | n.a. | 38 weeks | 41 weeks |
| Birth measures | W = 2645 g (z = 0.58), L = 48 cm (z = 0.52) HC = 31.3 cm (z = −0.57). | L = 53 cm (z = 0.61), HC = 35 cm (z = 0.04) | W = 3415 g (z = 0.23), L = 51 cm (z = −0.05), HC = 34 cm (z = −0.20) | n.a. | W = 3700 g (z = 0.61), L = 56 cm (z = 1.86), HC = 37 cm (z = 1.92) | W = 3660 g (z = −0.14), L = 52 cm (z = −0.44), HC = 34 (z = −0.90) |
| Onset of persistent diarrhea | First day of life | One year | Six weeks of life | First day of life | Six weeks of life | Second month of life |
| Disease course | Intractable diarrhea and failure to thrive, weighing 5710 g (z = −3.63) at one year. Breast milk feeding in the first year of life. No duodenal biopsy was obtained. |
Intractable diarrhea and failure to thrive from one year of age. No duodenal biopsy was obtained. |
Intractable diarrhea and failure to thrive. TBIL of 3.47 mg/dl (expected 0.1–1.20), direct bilirubin (DBIL) 3.01 mg/dl (0.0–0.3) prior to PN initiation. |
Intractable diarrhea and failure to thrive. PN and PEG tube feeding. Duodenal biopsies showed total villus atrophy and mild inflammation, and findings of TE on re-evaluation post-mortem. Birth of patient 1 to this family led to a diagnosis of TE. |
Intractable diarrhea and failure to thrive. Fully breastfed for six weeks. Hyperbilirubinemia (TBIL = 8.75 mg/dl, DBIL = 0.56 mg/dl) prior to PN initiation. |
Intractable diarrhea and severe failure to thrive weighing 3910 g (z −2.87) at three months with infant formula. Stool pH low (pH = 6.0), steatorrhea. Initial suspicion of cow’s milk protein intolerance. Esophagogastroduodenoscopy and colonoscopy at four months of age excluded inflammatory bowel disease; gastroduodenoscopy at six months revealed nearly absent EPCAM expression. |
| Age at definite diagnosis of TE/method | Two years/exome sequencing | Post-mortem, in retrospect | Three months/EPCAM sequencing | Post-mortem, in retrospect/immunohistochemistry | Nine weeks of age/EPCAM sequencing | Eight months/immunohistochemistry and exome sequencing |
| Age at last examination or death | Three years | Died age seven years | Died age 3.5 years from multi-organ failure | Died age eight years from catheter-related septicemia and multiple organ failure | Three years | Two years |
| Body measuresat last examination | W = 12.5 kg (z = −0.96) L of 82 cm (z = −3.4) HC = 49 cm (z = −0.34) |
W = 7.5 kg (z = −15.86). | W = 9.4 kg (z = −2.97), L = 81 cm (z = −3.22). | n.a. | W = 15 kg (z = 0.08), L = 92 cm (z = −1.47), HC = 50.7 cm (−0.05) | W = 10.45 kg (z = −1.23), L = 77.5 cm (z = −2.74), HC = 49 cm (z = −0.25) |
| Current treatment | ≈90% of calories and fluid by central venous catheter; pancreatic enzymes orally, at home. | n.a. | n.a. | n.a. | Family food (1277 kcal/day), PN for 12 h/day (800 mL, glucose = 12 g/kg, protein = 23.5 g/kg, lipids = 2 g/kg, respectively, 80 kcal/kg), PN paused every fourth day | Enteral nutrition: Solid low-protein foods (220 kcal/d and 8 g of protein/day), 550 mL Basic-p 17% + 15 mL Liquigen/d, approximately 578 kcal/d). PN for 12 h/day (glucose = 2.5 g/kg, amino acids = 2.9 g/kg, lipids = 0.8 g/kg, corresponding to 283 kcal/d) |
| Current status | Persistent diarrhea. Psychomotor development is age-appropriate. | Formed to mucous stools 1–3 times/day, abdomen extended with weakened peristalsis. Age-appropriate psychomotor development. | Formed to mucous stools 2–3 times/day, abdomen distended but soft, no palpable resistance. Age-appropriate psychomotor development. | |||
| Additional findings | AST elevation (46.5 U/L (0–32)) with PN. | Ventriculostomy for aqueduct stenosis. Marked scoliosis. | Persisting mild acidosis (pH = 7.31), mild AST, and ALT elevation. | |||
L, length; W, weight; HC, head circumference; n.a., not available; N.A., not applicable; PN, parenteral nutrition; bold font indicates findings elaborated in the text.