DrMehak , DrVenkat , DrBhanu Vikraman Pillai (;Paed gastro)
DrSheela Nampoothiri(Paed Genetics ) DrC Jayakumar
AIMS KOCHI
Three month old infant, second child of third degree consanguinous parentage who was developmentally normal, partially immunised presented with loose watery stools since 16 th day of life. Birth weight was 2.86kgs. Ba was started on topfeeds which were continued for 3-4 days said to be due to inadequacy of breast milk
Ba used to pass loose watery stools after each feed but mother was reassured it was normal. By day 16 of life, mother realised that the ba passes large quantities of loose watery and foul smelling stools at times forcefully .On day 18 of life, she noticed fast and noisy breathing and the ba was shifted to an NICU where he was supported on CPAP and treated with IV antibiotics due to pneumonia
Ba was NPO on Day 1 of admission and he was symptom free . Ba was discharged on Day 22 of life and Day 25 of life, there was increase in the frequency of loose stools with the ba now passing stools twenty to twenty five times a day.
At this juncture as per advice breast feeding was stopped and topfeeds was started However, there was no remission of symptoms.
Trials with brands of formula milk also didn’t keep him
On Day 30 child developed severe degradation with oliguria and showed toAIMS
Differentials that we considered were–
Cow Milk Protein Allergy
Lactose Intolerance
Cystic Fibrosis
Immunodeficiency Syndromes
IPEX syndrome
Abetalipoproteinemia
VIPoma
Neuroblastoma
Congenital Diarrhoea
At admission ba has all the features of severe dehydration with Perinad small excoriation
Auxology showed weight, length and head circumference were less than -3SD.
No facial dysmorphism
Systemic examination was normal.
Labs
Leukocytosis with elevated
CRP of 16.37 mg/L.
LFT amd RFT were normal.
Serum Bicarbonate was low and serum
Na, K and Cl were all elevated.
ABG showed metabolic acidosis.
Peripheral smear showed neutrophilic leukocytosis.
Sweat Chloride was normal.
Stool studies showed positive reducing substances and occult blood.
USG Abdomen was normal.
On suspicion of CMPA, he was kept NPO for 24 hours and then slowly introduced with Neocate feeds.Complete hypoallergenic formula
But diarrhoea recurred after increasing the feeds to 60mL from 45 ml
T OGDscopy was done and found to be grossly normal.
Sigmoidoscopy showed normal mucosa and oil and stool floating in the colonic lumen. Repeat USG showed distended fluid filled rectum.
Total, LDL and HDL Cholesterol were elevated.
Genetic Study revealed homozygous missense variant of PCSK1 gene associated with Proprotein convertase 1/3 deficiency which is an autosomal recessive disorder associated with neonates and younger children presenting with severe malabsorptive diarrhoea and failure to thrive and older children presenting with obesity and polyendocrinopathies like hypothyroidism, hypogonadism, adrenal insufficiency, diabetes insipidus and growth hormone insufficiency.
PCSK1 gene encodes for proprotein convertase 1/3 enzyme that is responsible for conversion of propeptides into bioactive forms.
13 cases have been studied so far with 10 having history of consanguinity and all of the children presenting with dehydration, severe malabsorptive diarrhoea and metabolic acidosis in the first 2 months of life with most cases requiring prolonged total parenteral nutrition.
While the infants had weight <-3SD, the older children were obese. By ~18 months of age, Diabetes Insipidus was diagnosed in 8 cases. 3 of the male children had hypogonadism with micropenis. Central adrenal insufficiency was found in 8 children between 1 month to 5.5 years of age with 7 children receiving daily hydrocortisone therapy. Central hypothyroidism was observed in 8 cases while Growth Hormone deficiency was observed in 4 cases. Hormonal studies were this ba were normal at present.
Ba has been started on Pancreatin(combination of amylase, lipase, protease and lactase) supplementation and is being continued on Neocate feeds.
Congenital Diarrhoea and Enteropathy [CODEs] are rare entities manifesting as severe large volume diarrhoeas at birth or after the neonatal period. These can be mainly divided into secretory diarrhoeas or Malabsorptive osmotic diarrhoeas that improve with fasting as in this case.
Dietary challenges are also important for malabsorptive diarrhoeas. Many infants present with metabolic acidosis and dehydration. Careful history taking can be the key to diagnosis. History of polyhydramnios in the antenatal period is suggestive of congenital chloride/sodium diarrhoea. History of consanguinity and family history of similar of similar complaints is also important. Similarly, on examination, facial dysmorphism can provide an essential clue.
Carry Home Message
As a pediatrician, we should not overlook complaints of loose stools in infancy. History taking especially of basic pointers like consanguinity can prove to be the key for the diagnosis of even the rarer disease entities.