A Child with Failure to Thrive
description
Transcript of A Child with Failure to Thrive
![Page 1: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/1.jpg)
Circadian Rhythm - Temperature
![Page 2: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/2.jpg)
![Page 3: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/3.jpg)
QUESTION“How are you feeling?”
• Very drowsy and would love a little nap
• Wide Awake and rearing to go
• Asleep – do not disturb
BLUE
YELLOW
WHITE
NOW!
![Page 4: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/4.jpg)
A Child with Failure to Thrive
Colin WallisRespiratory Unit
Great Ormond Street Hospital
![Page 5: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/5.jpg)
• FTND - asymmetrical IUGR
• Birth weight 1.9 kgs < 0.4th centile
• Length 42 cms < 0.4th centile
• OFC 33.2cms > 25th centile
• Ventilated for 3 days and discharged home in air at 14 days
![Page 6: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/6.jpg)
• FBC and serum biochemistry were normal
• TORCH screen - negative
• Some episodes of fasting hypoglycaemia
• No catch up growth despite adequate caloric intake via
• NGT feeds
Readmitted 10 days later to local hospital for poor weight gain and intermittent diarrhoea
Referred to GOSH for further investigations
![Page 7: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/7.jpg)
QUESTION“What test is likely to be
most useful?”• Coeliac screen
• Endoscopy
• Sweat test
BLUE
YELLOW
WHITE
NOW!
![Page 8: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/8.jpg)
Coeliac screen – negative
GI endoscopy and colonoscopy were normal including histology of large bowel
Sweat test - positive Na 60 mmol/l ; Cl 111 mmol/l
![Page 9: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/9.jpg)
A diagnosis of Cystic Fibrosis was made
• CF genotype - R1162X/R1162X
• Stool elastase - < 15 mcg/g {>200mcg}
• Positive sweat test
•Usual multivitamin supplementation and prophylactic antibiotics
•Adequate caloric intake with creon supplementation
• Overnight NGT and top-up feeds
![Page 10: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/10.jpg)
QUESTION“What next?”
• Remove ng tube and monitor weight gain
• Insert gastrostomy for long term feeding
• Consider diabetes
BLUE
YELLOW
WHITE
NOW!
![Page 11: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/11.jpg)
• Ng tube was removed with very poor feeding and further loss of weight
• No evidence of diabetes
• Gastrostomy inserted at age 3 years
![Page 12: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/12.jpg)
…… and so over the next 2 years ………….
•Overnight feeds with additional boluses during the day
•Persisting FTT with weight and height well below 0.4th centile and intermittent diarrhoea
•No chest infections - only growth of Ps. aeruginosa at 4 years of age
At 5 years :
Weight - 12 kgs <0.4th centile
Height - 95 cms <0.4th centile
FVC 117% of predicted
FEV1 117% of predicted
![Page 13: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/13.jpg)
![Page 14: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/14.jpg)
QUESTION“Does she deserve further
investigation?”• Yes – Endocrine review
• Yes – Gastroenterology review
• No – This needs psychosocial input
BLUE
YELLOW
WHITE
NOW!
![Page 15: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/15.jpg)
For those of you who voted Endocrine:
• Skeletal survey at 5 yrs - delayed bone age 2.5 yrs
• Normal amino acid profile
• Growth hormone assay - normal
• Normal IGF1 & IGFBP-3
• Normal thyroid function tests
• Normal cortisol , insulin and glucose levels
• Normal NEFA and BOHB (rules out fatty acid oxidation
defects)
![Page 16: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/16.jpg)
For those of you who voted Gastroenterology:
• Stool elastase still very low• pH study normal - pH study - 0.5% reflux• Repeat upper GI biopsies suggestive of duodenitis with
mucosal eosinophilic infiltrate • Started on MCT feeds (peptamen) & PO Sodium
cromoglycate
• Improved stool consistency with occasional diarrhoea
• Introduction of dairy free diet
…. And the failure to thrive persisted….
![Page 17: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/17.jpg)
For those of you who voted Psychosocial:
• Psycho-social issues - Parental disharmony
• Father blamed mother for the CF in their child – refused to accept that he had a genetic role in the condition
• Suggested genetics counselling
![Page 18: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/18.jpg)
• Full term gestation
• Birth weight & length <2SD below mean
• Postnatal growth <2SD below mean for height & weight
• Triangular face (Craniofacial disproportion)
• Down turned corners of mouth
• Clinodactyly, and usually shorter digit than normal
• Scaphocephaly
• Hypoplastic mandible and small, crowded teeth
• Low set, small, or prominent ears
• Delays in bone age and poor muscle tone
Phenotypically resembles Russell Silver Syndrome
Genetics review
![Page 19: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/19.jpg)
Phenotypically resembles Russell Silver Syndrome
![Page 20: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/20.jpg)
Phenotypically resembles Russell Silver Syndrome
Common traits:
• Body asymmetry
• Growth hormone deficiency
• Hypoglycaemia in infancy and early childhood
• Late closure of the fontanelle
• Hypoplastic mandible and small, crowded teeth
• Low set, small, or prominent ears
• Delays in bone age and poor muscle tone
• Thin upper lip with down turned corners of mouth
• Syndactyly of toes
• Developmental delay
Are you sure this is CF?
![Page 21: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/21.jpg)
9 6 3
3132
46XX, homozygous for R1162X mutation
Mum – carrier for R1162X
Dad – not a carrier
![Page 22: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/22.jpg)
QUESTION “How are you feeling now?”
• Glad I don’t have to explain non-paternity to this family
• Ask genetics to approach the family
• I’m staying well out of this
BLUE
YELLOW
WHITE
![Page 23: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/23.jpg)
9 6 3
3132
46XX, homozygous for R1162X mutation
Mum – carrier for R1162X
Dad – not a carrier
Dad is the father
Child has uniparental disomy
What is Uniparental Disomy?
•UPD is the inheritance of both homologues of a chromosome pair from only one parent.•In 2/3 of cases the UPD is of maternal origin.•UPD can result in:
–the appearance of recessive disorders depending on the chr.–developmental and growth abnormalities (due to imprinting)–no apparent impact on the health of the individual.
![Page 24: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/24.jpg)
Genetics of Russell Silver Syndrome
• 10% of cases of RSS have maternal UPD7
• Genetically heterogeneous – 80% cases sporadic– (AD/AR/XL)
• RSS caused by matUPD7 gives a milder phenotype, but the feeding problems are more severe.
![Page 25: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/25.jpg)
Normal Meiosis
• Start with a cell with 46 chromosomes
• Sister Chromatid formation
• Meiosis I: the homologous pairs separate into two new daughter cells.
• Meiosis II: the replicated pair of sister chromatids separates into two new daughter cells.
![Page 26: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/26.jpg)
Meiotic Errors
Meiosis I error Meiosis II error
homologous pairs both travel into the same daughter cell.
chromatids will not separate and thus travel into the same daughter cell.
![Page 27: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/27.jpg)
QUESTION“How does UPD occur?”
• By Trisomic rescue
• By Monosomic resuce
• Gamete complementation
• Don’t know what you’re on about
BLUE
YELLOW
WHITE
Hold up nothingNOW!
![Page 28: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/28.jpg)
How does UPD occur ?
: CF Mutation on 7q31.2
Trisomic RescueFertilisation
following Meiosis II error
Monosomic Rescue
Fertilisation following Meiosis II
error
Gamete Complementatio
n
![Page 29: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/29.jpg)
How does UPD cause CF?
• Patient AA is homozygous for the R1162X (arginine-stop) mutation as she has inherited both chromosome 7’s from her mum.
• Children with this form of CF do not have normal AR risks for future pregnancies – recurrence risk very low
• Gasparini et al looked at the clinical course of 9 patients homozygous for this mutation:– Lung disease was mild-moderate– Higher rates of pseudomonas colonisation– Higher rates of ABPA– Pancreatic insufficiency was severe– And our patient also has Russell Silver syndrome
![Page 30: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/30.jpg)
Lessons and questions from an interesting case
• UPD is a rare but possible cause of autosomal recessive disorders
• We should be suspicious of FTT in CF with Russell Silver phenotype – but should we screen CF patients with unusual growth retardation for matUPD7 ?
• Should we be doing parental tests on all homozygous CF children?
• Testing DNA from parents and child can potentially uncover nonpaternity. Should this be discussed as part of informed consent ?
• Do these findings introduce new treatment options?
• Growth hormone therapy
• Nebulised or systemic gentamicin
• Be aware
![Page 31: A Child with Failure to Thrive](https://reader033.fdocuments.in/reader033/viewer/2022061121/546928c1af7959b6258b5a0c/html5/thumbnails/31.jpg)