Growth Disorder

Possible Anorexia, Vomiting, Failure to Gain Weight and Linear Growth Retardation
Short Summary

21-month-old female who was born at almost 29 weeks weighing only 650g and with birth height of 31 cm. Her major problems have been poor feeding, failure to gain weight and linear growth retardation. The poor feeding has been handled by an NG tube and subsequently, food administration through a direct gastric tube via a gastrostomy. She gradually gained weight to the extent of being overweight for her height. Laboratory evaluation revealed low absolute numbers of neutrophils low lymphocyte count. Endocrynology and Genetics workup were normal. In the expert's conclusion, the patient suffers possible anorexia and failure to progress normally with linear growth. The short stature may be either primary or secondary.

Patient's Questions

1. What’s causing the vomiting and how can it be handled?

2. Are the feeding problems caused by the vomiting?

3. If not, what is the cause of the feeding problems and how can it be handled?

4. Is the short stature caused by the feeding problems?

5. If not, what is the cause of the short stature and how can it be handled?

Medical Background

• The patient was born January 2008 prematurely. Week 28+6, weight 650g, 31cm long (IUGR).

• We had no major problems in the NICU or premature ward. (see summary of that hospitalization for more details as needed)

• We were released on 22 April after 3 months. The patient was 41 weeks old, weight 2kg.

• We did not have any problems either till end of May. She gained a kilo in a little more than a month. She was not a great eater (never really asked for food like a regular child) but she succeeded in eating circa 130cc/kg/day.

• She was eating breast milk, then partially breast milk, partially formula. Around the same time she started to vomit. The more she vomited, the less she ate. We tried different formulas with no great success.

• By July we were hospitalized under the heading of failure to thrive and anorexia. The following work up was done during this hospitalization.

ultra-sound for pyloric stenosis – normal
renal function – normal
metabolic disorders – normal
Brain MRI – normal
Barium contrast study – showed mild reflux

• For several months around the same time she was treated with Zantac and Losec (anti reflux medication) which had no visible effect.

• At the end of 2 weeks of hospitalization, she gained a bit of weight and we were released while nothing was actually solved.

As the anorexia and vomiting continued and she was now 4 months of corrected age and still 3 kg, we put an NG tube for circa 3 weeks. She gained weight but she vomited a lot (about 3 to 5 times per day).

• We therefore arrived at considering the gastrostomy. We did a last trial of feeding her as much as she wanted when she would want (cry). She ate about half of what she should have and lost close to 300 gr in less than a week. She was now about 5 months of corrected age, and weighed 2.8 kg. We did the gastrostomy.

• The patient gained weight nicely in the following months with the gastrostomy but never ceased to vomit between 1 to 5 times per day. We were advised against the fundoplication on the basis that it has its own side effects and she was gaining weight.

• It is to be noted that all along her development has been normal for her corrected age. Both motor and cognitive.

• In April, the patient was now 1 year of corrected age and 15 month of chronological age. She weighed 7.2 kg and was only 61cm long. She was fat for her lengh and looked fat. There was no change in terms of the vomiting and she was no longer eating by mouth at all. All her food was being given to her straight through the gastrostomy tube. No other food, spoon or anything else would be accepted by her either.

• We therefore followed a protocol for weaning a child off of a gastrostomy (48 hours wean). She hardly ate the first 2 days but then restarted with oral feeding by bottle and within a few days we stopped feeding her by tube completely.

• She was not eating enough but as we were told she needed to lose weight we continued hoping that things would adjust themselves. After 4 months the patient had gone down to 6.5kg very slowly but had not gained or regained any weight. She would eat 500cc of Nutren Junior in a day whereas she needs about 650 to 700 to gain weight. Vomiting continued as before.

• Very recently we started to complete her meals by using the tube and she is slowly regaining weight. However she still vomits daily and weight gain is not easy.

• An important thing to note is that it is visible on her growth chart that she only grows in height/length when she receives sufficient amount of calories. Otherwise there is no growth whatsoever.

• She eats only the Nutren Junior of Nestle. She does not eat with a spoon and eats no solid food. Nothing enters her mouth except her own fingers or cloth that she sucks on. Or of course the nipple of the Nutren bottle. She lightly licks some food. We work on this all the time.

Her vomiting is unchanged. It can happen right after the food or 3 hours after a meal. It also happens while she sleeps. It can and does also happen on a completely empty stomach and only mucus or water comes out. There is no rule.

• Eating causes the appearing of mucus instantly. When she drinks about 50cc you can hear wet mucus in her throat/way and this is usually when she will stop eating.

• Since June 2008 till today there were two periods of times (two weeks each) where the patient didn’t vomit at all. Both occurred after a two days fasting (once after she had the gastrostomy insertion operation and was fed by IV and once after the 48 hours wean of gastrostomy feeding).

• We also had her tested for allergies and she is not allergic.

Endocrynology workup
The patient was seen by 2 endocrynologist with regards to her very short stature.
Glucaton test indicated growth hormones normal.
X rays were done her bone age and diseases (see enclosed). We were told they were unconclusive.

We were referred to Genetics
Genetics workup
• FD negative
• Sweat test for CF negative
• Bloom negative
• Russel Silver negative
• Cockayne Syndrome negative
• Check of many genetic disorders done in the US (see attached) found nothing as well.

Expert's Opinion

The patient is a 21 month old female who was born by C section to a 38y old mother (1st delivery, second pregnancy) at almost 29 weeks weighing only 650g and with birth height of 31 cm. (Her parents average height was 157cm). She was born at Apgar 6 at one minute and seven at five minutes. She received CPAP and 26% oxygen. Her physical examination appeared normal.

Head ultrasound was essentially normal. She suffered episodes of apnea and bradycardia for more than 2 months for which she received Theophylline. She had 2 possible infection episodes one was a sepsis workup at day 1 of life and the other at day 11.

Mother received 2 courses of steroids beginning at 22-23 weeks gestation for IUGR. No mention of head circumference at birth. Neurological assessment was apparently normal, in and after NICU.

Her major problems since have been: poor feeding, failure to gain weight and linear growth retardation. The poor feeding has been handled by an NG tube and subsequently, food administration through a direct gastric tube via a gastrostomy. I understand that weight gain improved dramatically following this mode of nutrition. She gradually gained weight to the extent of being overweight for her height. This would suggest that the patient may not have a problem in absorbing nutrients but rather a possible aversion to food as well as failure to progress normally with linear growth. Laboratory evaluation at 6 and 8 months revealed low absolute numbers of neutrophils in the first evaluation and low lymphocyte count at both assessments. No other evaluations were provided. Various genetic testing for Familial dysautonomia, Cockayne syndrome, Bloom syndrome and Russel Silver syndrome were normal as well as whole genome scanning using CGH array and evaluation of copy number variants did not reveal an obvious anomally. Sweat chloride test for CF was negative as was the metabolic screen. Further, transcription coupled DNA repair was tested and found normal.

Answers to parents questions
1. Vomiting small amounts of food is not uncommon in infancy and more so in children who receive feeding through an NG or a gastrostomy. What is important is the frequency and amount of nutrition lost. I understand that inspite of the gastric feeding, the patient gained weight very well, suggesting that the amount of vomiting was not critical. I therefore do not think that the feeding problems are caused by the vomiting. To reduce vomiting, in such patients, it is recommended to use smaller volumes more frequently.

2. Feeding in infants and children is a complex process. It requires timely introduction of various foods, like solids, in order for a normal eating pattern to take place. Sometimes by missing a window of opportunity, food aversions and feeding disorders may develop. Physicians have to rule out first mechanical or other known causes of feeding disorders which was largely already done in the case of the patient.

3. Short stature may be in general terms either primary or secondary. Secondary growth retardation may be seen in very sick babies or the ones who do not get sufficient calories. Without the consumption of solid foods it is hard to introduce sufficient amounts of protein and other nutrients in the diet. Gradual dietary modifications to change feeding habits may prove beneficial.

4. There are many causes for primary growth retardation. Short stature may be a feature associated with several syndromes. Most were excluded in the patient's case by doing CGH and other more specific tests. The lack of neurological involvement also excludes many possible syndromes.

In conclusion, the patient suffers possible anorexia and failure to progress normally with linear growth. The fact that she was born small for gestational age and she failed to improve her height in spite of increased weight, raises the possibility that she might have an underlying disorder. I would therefore recommend the following.

1. A more consistent assessment of lymphocyte and neutrophil counts should be carried out. On 2 occasions the absolute lymph count was low.

2. Evaluation of the immune system including lymphocyte markers and mitogen responses should be performed.

3. A skeletal survey should be done to exclude skeletal dysplasia such as cartilage hair hypoplasia or others (bone age is insufficient).

4. If lymphocyte and neutrophil counts are consistently low, a bone marrow should be considered.

5. Endocrine abnormalities should be checked thoroughly (parathyroid, thyroid, adrenal etc.)

6. Molecular analysis for RMRP and AIRE genes should be considered.

7. I recommend the family consults with Dr. Raz Somech, an Immunologist and former student of mine. He can perform most of the tests mentioned and if he needs help he can contact me for follow-up.
If Safra is not an option then I would refer them to Dr. Ilan Dalal at Wolfson, another Immunologist and former student of mine.

8. The family should consult with specialists feeding disorders. Dr. Raanan Shamir is probably a good suggestion from Schneider.