1. MALABSORPTION

2. Malabsorption features in the patient Chronic diarrhoea Abdominal distension Failure to thrive – Severe acute malnutrition (kwashiorkor) Hypoproteinaemia with severe hypoalbuminaemia Severe anaemia Steatorrhoea

3. Causes of Malabsorption Intestines Congenital intestinal digestive enzyme deficiencies – Congenital lactase deficiency, Sucrase-isomaltase deficiency Congenital absorptive or transport defects – Microvillus inclusion disease, Glucose-galactose transporter deficiency Mucosal surface injury – Celiac disease, Crohn disease, Giardiasis, Cryptosporidium, postinfectious diarrohea Abnormal intestinal lymphatic drainage – Primary intestinal lymphangiectasia

4. Causes of Malabsorption Pancreas Pancreatic insufficiency – Cystic fibrosis, Shwachman-Diamond syndrome Liver Chronic cholestasis – Biliary atresia, Alagille syndrome

5. Diagnoses to think about in patient Pancreatic insufficiency Shwachman-Diamond syndrome – Steatorrhoea – FTT – Low neutrophil count, severe anaemia, mild thrombocytopenia Cystic fibrosis – FTT – Chronic diarrhoea – Delayed passage of meconium

6. Shwachman-Diamond syndrome A rare autosomal recessive disorder Due to mutations in Shwachman-Bodian-Diamond (SBDS) gene on chromosome 7q11 Second most common cause of exocrine pancreatic insufficiency in children Estimated incidence of 1 in 75,000 in the US Characterised by – Exocrine pancreatic insufficiency – Bone marrow hypoplasia – Bony changes – metaphyseal dysostosis – Leukemia predisposition

7. Shwachman-Diamond syndrome Clinical features – Short stature (height & weight < 3 rd percentile) – Steatorrhoea – Dry skin (eczema) – Hepatomegaly – Progressive spinal deformities, throracic cage defects, digit defects

8. Shwachman-Diamond syndrome - Investigations FBC neutropenia - >80%, cyclic or persistent Anaemia – mild, normocytic normochromic Mild thrombocytopenia LFTs – hypoalbuminaemia, elevated liver enzymes Screening test – Sweat test – to rule out Cystic fibrosis – 72hrs fat measurement or excessive fat globules on stool microscopy – Faecal elastase Specific tests – Pancreatic stimulation tests – Pancreatic U/S and CT – small abnormal pancreas

9. Cystic Fibrosis Cystic fibrosis is a disease of exocrine gland function that involves multiple organ systems Autosomal recessive disorder Whites affected most commonly Reported in blacks in US, South Africa, Cameroon, Kenya and Senegal

10. CF - mutations ‘ Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations on chromosome 7 Most common defect is Delta F508, a deletion of 3 base pairs resulting in absence of phenyalanine at codon 508 (70% of caucasians) In Africans, most common mutation is 3120 +1G(A) – In the US, found in 12.3% of African American CF chromosomes (Macek et al, 1997) – In southern African black patients (Carles et al, 1996)

11. Cystic fibrosis Gene codes for a CFTR protein, a cAMP regulated chloride channel found on the apical portion of mucosal epithelial cells Affects the airways, pancreatic ducts, biliary tree, intestines, vas deferens and sweat glands Results in – chronic respiratory infections – pancreatic enzyme insufficiency, and – associated complications in untreated patients

12. Cystic fibrosis Gastrointestinal symptoms – Meconium ileus – Abdominal distention – Increased frequency of stools – Failure to thrive (despite adequate appetite) – Flatulence or foul-smelling flatus, steatorrhea – Recurrent abdominal pain Respiratory and GUT symptoms

13. CF - DIAGNOSIS Either – positive genetic testing or – positive sweat chloride test findings and – 1 of the following: Typical chronic obstructive pulmonary disease (COPD) Documented exocrine pancreatic insufficiency Positive family history (usually an affected sibling)

14. Treatment – alternative formulas FormulaDescriptionIndication Soy based formulaMade using soy protein. Do not contain lactose Galactosaemia, congenital lactase deficiency, vegetarians Lactose free formulasLactose freeGalactoasemia, congenital lactase deficiency, primary lactase deficiency For preterm babiesHigher calories, proteins, vitamins and minerals than regular infant formula Prematurity Hypoallergenic formulas (protein hydrolysate formulas) Semi elemental hypoallergenic infant based on extensively hydrolysed whey protein Allergies to milk protein, eg cow’s milk protein allergy Elemental feedsAmino acid based – essential and non essential amino acides Severe gastrointestinal tract impairment

15. Comparison of different breastmilk and different formulas COMPONENTBREAST MILKREGULAR INFANT FORMULA ALFARE FORMULAINFASOY DescriptionSemi elemental hypo allergenic formula Soy protein; lactose free Calories (Kcal/100ml)70687067 Protein/100ml1.11.52.11.8 Carbohydrate/100ml6.87.27.76.9 (sucrase, corn syrup solids) Fat/100ml4.52.93.6 Fat type Long chain triglycerides,Linol eic acid, palmitic acid Medium Chain Triglycerides, Docosahexaonoic acid, Linoleic acid, linolenic acid Linoleic A, Linonlenic acid Casein:whey ratio4:66:4Whey only Sodium mg/100ml15213519 Potassium mg/100ml60708872 Calcium mg/100ml35555467 Iron mg/L0.5120.712

16. References Carles S et al, 1996, First report of CFTR mutations in black cystic fibrosis patients of southern African origin, J Med Genet, 33:802-804 Macek M et al, 1997, Identification of common Cystic Fibrosis mutations in African Americans with Cystic Fibrosis increases detection rate to 75%, Am. J. Hum. Genet. 60:1122-1127

17. THE END