MALABSORPTION

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, postinfectiousdiarrohea • Abnormal intestinal lymphatic drainage • Primary intestinal lymphangiectasia

4. Causes of Malabsorption Pancreas • Pancreatic insufficiency • Cystic fibrosis, Shwachman-Diamond syndrome Liver • Chronic cholestasis • Biliaryatresia, 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 – metaphysealdysostosis • Leukemia predisposition

7. Shwachman-Diamond syndrome • Clinical features • Short stature (height & weight < 3rd 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, normocyticnormochromic • 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 • Autosomalrecessive 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 • Meconiumileus • 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

15. Comparison of different breastmilk and different formulas

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

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