Inherited Pancreatic Disorders of Childhood

From this link: http://www.pancreasfoundation.org/cgi/csNews/csNews.cgi?database=learn_genetics.db&command=viewone&id=1&op=t




Inherited Pancreatic Disorders of Childhood
Peter R. Durie, M.D., FRCPC

There is an extremely wide spectrum of inherited pancreatic disorders in childhood. Depending on the condition symptoms can develop at any time from birth to adulthood. The pancreas makes more than 25 different digestive enzymes which are secreted into the intestine to break down dietary protein, fat and starches into simpler molecules so that they can be absorbed. In fact, the pancreas has a tremendous reserve capacity - more than 95% of the function of the pancreas must be lost before the pancreas fails and symptoms of bloating and maldigestion develop. Children with digestive problems due to failure of the pancreas have to take enzyme replacement therapy with meals as well as additional fat soluble vitamins. The large pancreatic reserve also means that children can have a severe pancreatic problem without experiencing any problems with digestion.
The exocrine pancreas is not fully developed at birth. In fact, all healthy infants show some degree of maldigestion due to the fact that the pancreas is immature and does not have the same ability to produce enough enzymes. This is particularly true for starch and fat digestion. However, the pancreas matures after birth and by two years of age it is functioning in the same way as an adult pancreas. The immature pancreas appears to have no adverse effects on healthy children, but can have a major impact when children become malnourished or very ill.
Cystic fibrosis (CF) is, by far, the most common inherited pancreatic disease of childhood. It accounts for about 90% of childhood onset pancreatic disorders. CF affects many other organs as well and the most common cause of poor health and death is due to progressive lung disease. The CF pancreas begins to get damaged when the affected child is still in the mother’s womb. The small tubes inside the pancreas which allow digestive enzymes to reach the intestine get blocked with mucus and protein and the pancreas became badly scarred and shrinks. Many children with CF have evidence of severe pancreatic failure immediately following birth, and by two years of age 90% of CF are diagnosed - usually with severe malnutrition. Approximately 85% of all people with CF have pancreatic insufficiency and need to take pancreatic enzymes with meals. A lot is known about the genetic cause of CF. The CF gene, which is on chromosome 7, was identified in 1989. The most common CF-disease causing genetic mistake in this gene is called DF508, and is identified in approximately 70% of CF chromosomes worldwide. However, there are more than 1000 additional genetic mistakes in the CF gene, many of which are extremely rare. A lot of research is being done to try to correct the genetic disorder with gene therapy, and to discover ways of getting round the genetic disorder using special drugs.
Shwachman Diamond syndrome (SDS) is the next most common inherited cause of pancreatic failure in childhood. It is much less common than CF and accounts for about 5% of inherited causes of pancreatic disease. This condition also affects other organs including the bone marrow (which makes blood cells), the skeleton and the liver. Children with SDS are very short and are at risk of experiencing severe infections and a particularly severe form of leukemia. Unlike CF, the gene that is responsible for SDS has not yet been identified. However, recent research shows that the SDS gene is also located on chromosome 7. The pancreatic problem is quite different from CF. The cells that make enzymes (acinar cells) don’t develop properly.
After CF and SDS, other causes of inherited pancreatic disease are extremely rare. They include Johansson Blizzard syndrome, Pearson’s bone marrow syndrome and hereditary pancreatitis. It is interesting to note that the hereditary pancreas gene is on chromosome 7 as well. This is a coincidence!
In extremely unusual circumstances a child may be born without any pancreas - which includes both the digestive (exocrine) and insulin producing (endocrine) components of the pancreas. This problem is not compatible with life.

Peter R. Durie, M.D., FRCPCProfessor, Department of PediatricsUniversity of TorontoDivision of Gastroenterology/NutritionHead, CF Research Group, The Research InstituteThe Hospital for Sick Children



For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Steatorrhea and pancreatic insufficiency in Shwachman syndrome.

this is very old….. more and more archives are making it to the net as various companies and journals get them added…..interesting, nonetheless.


Steatorrhea and pancreatic insufficiency in Shwachman syndrome.
Gastroenterology. 1982; 83(1 Pt 1):22-7 (ISSN: 0016-5085)
Hill RE; Durie PR; Gaskin KJ; Davidson GP; Forstner GG
Fat absorption was assessed on two or more occasions in 12 of 14 patients with Shwachman syndrome. Of 11 children who initially had steatorrhea, 6 were subsequently found to have normal fat excretion. In 10 of these 11 patients the last estimate was smaller than the initial estimate after an interval of 0.3-12.7 yr. The most dramatic improvement occurred under 4 yr of age but improvement appeared to continue over a more extended period where sufficient follow-up was available. All patients had pronounced pancreatic insufficiency as tested by duodenal drainage corrected by nonabsorbable marker under stimulation with cholecystokinin and secretin. Pancreatic lipase secretion was assessed in 3 patients with steatorrhea and 5 without steatorrhea (73% of the surviving patients) using a sensitive assay which used maximum stimulation with colipase. Pancreatic lipase secretion was less than 2% of normal mean secretion in the steatorrheic patients and ranged from 3.7% to 13.6% in the patients without steatorrhea. These results indicate that fat absorption improves in the majority of patients with Shwachman syndrome and appears to be associated with marginal improvement in pancreatic lipase secretion. Due to the occult nature of bowel complaints in older patients, the diagnosis may be overlooked unless careful screening for pancreatic function takes place.

Pancreatic Exocrine Function Tests

Pancreatic Exocrine Function Tests

There is a brief overview of the topic....with a subscription, you can read the entire thing. Excellent info on the testing.

Essential Facts for Managing Pancreatic Insufficiency

Solvay has another great PDF brochure that is wonderful! This is a great resource to bring to teachers and school nurses. It goes into the basics of managing pancreatic insufficiency(PI), explaining what PI is, how pancreatic enzyme supplements work, symptoms of PI and correct dosage of enzymes.

Essential facts for managing Pancreatic Insufficiency

Fecal Fat Testing - 72 hour

Very often, the fecal fat test is one of the first tests done when starting the diagnostic process for a child with failure to thrive. Children with Shwachman-Diamond Syndrome have excess fat in their stools due to pancreatic insufficiency.


Fecal Fat Testing from Medline

Stool Fat Test

AtoZ Stool fat Test

Exocrine Pancreatic Insufficiency Support List

There is a new support list for those affected by Exocrine Pancreatic Insufficiency.

Exocrine Pancreatic Insufficiency

Prevalence of Pancreatic Insufficiency in Inflammatory Bowel

I have this one in full-text.

Prevalence of Pancreatic Insufficiency in Inflammatory Bowel
Diseases. Assessment by Fecal Elastase-1


Abstract Pancreatic insufficiency (PI) may be an extraintestinal
manifestation of inflammatory bowel diseases
(IBD). We report the results of a cross-sectional study that
was carried out to investigate both the prevalence of PI in
IBD patients and its clinical course over a 6-month followup
period. In total, 100 Crohn’s disease (CD) patients, 100
ulcerative colitis (UC) patients, and 100 controls were
screened for PI by the fecal elastase-1 (FE-1) test. The
decision limits employed were: £ 200 lg/g stool for PI
and £ 100 lg/g for severe PI. Patients with abnormal FE-1
values were re-tested after 6 months. Odds ratios (OR) for
PI were estimated by unconditional logistic regression
analysis. PI was found in 22 UC and 14 CD patients. The
OR for the FE-1 test £ 200 lg/g was 10.5 [95% confidence
interval (CI): 2.5–44.8] for IBD patients compared to
the controls. The risk of PI was related to three or more
bowel movements per day (OR = 25.0), the passage of
loose stools (OR = 7.7), and previous surgery (OR = 3.7).
At the 6-month follow-up, FE-1 values became normal in
24 patients and showed persistently low concentrations in
12. These patients had a larger number of bowel movements
per day (OR = 5.4), previous surgery (OR = 5.7),
and a longer duration of the disease (OR = 4.2). PI is
frequently found in IBD patients, particularly in those with
loose stools, a larger number of bowel movements/day and
previous surgery. PI is reversible in most patients, and
persistent

Pancreatic Enzyme Pharmacotherapy

I have this article in full-text.


Pancreatic Enzyme Pharmacotherapy
Marcus Ferrone, Pharm.D., Massimo Raimondo, M.D., and James S. Scolapio, M.D.

Supplemental pancreatic enzyme preparations are provided to patients with
conditions of pancreatic exocrine deficiency such as chronic pancreatitis and
cystic fibrosis. These patients frequently experience steatorrhea, which occurs
from inadequate fat absorption. The delivery of sufficient enzyme
concentrations into the duodenal lumen simultaneously with meals can
reduce nutrient malabsorption, improve the symptoms of steatorrhea, and in
some cases alleviate the pain associated with chronic pancreatitis. Current
clinical practices dictate administration of lipase 25,000–40,000 units/meal by
using pH-sensitive pancrelipase microspheres, along with dosage increases,
compliance checks, and differential diagnosis in cases of treatment failure.
Despite the large number of specialty enzyme replacements available
commercially, many patients remain dissatisfied with standard therapy, and
future developments are needed to optimize treatment in these individuals.
Key Words: pancreatic enzymes, pancrelipase, pancreatitis, cystic fibrosis.
(Pharmacotherapy 2007;27(6):910–920)

Celiac and Pancreatic Insufficiency

This is an excellent article on Celiac and Pancreatic insufficiency.

Coeliac disease and pancreatic exocrine insufficiency

Click the above link for the entre article. Below is a small excerpt:

Historically, after diagnosis and the introduction of a gluten free diet, coeliac disease patients who experienced ongoing gastrointestinal symptoms were frequently suspected of failing to comply with their dietary restrictions.
However, evidence from a new study shows that around one third of these patients actually have a severe pancreatic exocrine insufficiency, which can be successfully managed by enzyme replacement therapy. This important finding can help substantially improve the quality of life of these patients.

Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed?

I have the full-text PDF of this article. VERY interesting!

Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed?


Exocrine pancreatic insufficiency is frequently associated with diabetes, with high prevalence in both insulin-dependent or insulin-independent patients. Exocrine pancreatic failure has often been perceived as a complication of diabetes. In contrast, recent clinical observations lead to the notion that nonendocrine pancreatic disease is a critical factor for development rather than a sequel to diabetes. The incidence of diabetes caused by exocrine pancreatic disease appears to be underestimated and may comprise 8% or more of the general diabetic patient population. Nonendocrine pancreas disease can cause diabetes by multiple mechanisms. Genetic defects have been characterized, resulting in a syndrome of both exocrine and endocrine failure. Regulation of beta-cell mass and physiological incretin secretion are directly dependent on normal exocrine function. Algorithms for diagnosis and therapy of diabetes should therefore address both endocrine and exocrine pancreatic function.

The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype.

I have the full-text PDF of this one.

The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype.

(Table is included in full-text article.)Cystic fibrosis (CF) is the most frequent cause of exocrine pancreatic insufficiency in childhood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes CFTR protein that functions as cyclic AMP-dependent chloride channel allowing the passage of anions and secondarily water into the lumen of pancreatic ducts. Luminal chlorides are exchanged for bicarbonates. The lack of CFTR channel or its disrupted function (being the consequence of CFTR gene mutations) results in reduced volume of more acidic secretion. It has been suggested that such a situation leads to the precipitation of highly concentrated protein-containing secretion with obstruction and organ damage. The intensity of this process determines the progression of the disease. Steatorrhea is the significant symptom of classical form of CF. Residual pancreatic secretion in a subset of patients, however, allows for normal lipid digestion and absorption. Previous cross-sectional clinical studies estimated that about 85-90% of CF patients in preschool, school and older age are pancreatic insufficient. More frequent detection of mild and nonclassic forms of CF leads to higher frequency of pancreatic sufficiency (PS). The potential decline of exocrine pancreatic function, however, should be always considered. All PS patients with at least one severe or unknown CFTR mutation should be longitudinally assessed for the progression of pancreatic dysfunction. Recurrent acute and chronic pancreatitis is not a rare clinical condition in PS patients with PS: it might be the presenting symptom, even preceding CF diagnosis by several years. Potential appearance of this complication in individuals with pancreatic insufficiency demands elucidation.

Article: MRI Findings of the Pancreas in patients with SDS and mutations in the SBDS gene

Magnetic resonance imaging findings of the pancreas in patients with Shwachman-Diamond syndrome and mutations in the SBDS gene.
Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
Pancreatic MRI was evaluated in 14 patients with a clinical diagnosis of Shwachman-Diamond syndrome, and the findings were correlated with Shwachman-Bodian-Diamond gene (SBDS) genotype. The findings suggest that patients with mutations in the SBDS gene have a characteristic magnetic resonance imaging pattern of fat-replaced pancreas and that SBDS mutations are unlikely in patients without this pattern.

This article contains charts on how each of the 14 patients pancreatic function was assessed. It lists all 14 patients and how each one’s pancreatic function was assessed and then lists the criteria for their SDS diagnosis. It also lists their neutrophil count (range) and height Z-score. In another chart, it lists how long they were on enzymes--- i.e. lists the age at which the person became pancreatic sufficient. One child was 4 years old when she came off of enzymes (i.e. she was on enzymes until age 4) and another one was 5 years old. Two came off of enzymes at 11 years and one at 22 years, one at 29 years, 3 never took enzymes and the rest are on on-going enzyme replacement.

There were 14 patients. 10 males and 4 females. 13 of them were diagnosed at a median age of 18 months….but one was referred to them at age 13 for suspected SDS. One of the patients was diagnosed with type I diabetes at age 15. With all of our diabetes talk recently, I thought that was an interesting note. The article says hat all patients with SBDS mutations showed fatty pancreas on MRI—the patients without the SBDS mutations and proven PI had NORMAL pancreatic MRIs.

We Take Enzymes

We Take Enzymes
We Take Enzymes was first written when Pattie’s sons were in pre-school and wondering why they had to take enzymes. In the first construction paper draft, Sean and Joseph helped with the text and drew the pictures in crayon. This book was read every day and helped them to understand the need for enzymes. This book educates young readers on the importance of taking enzymes and how these enzymes aid digestion. Told from Sean and Joseph’s perspective, this book will engage young readers with Shwachman-Diamond Syndrome and Cystic Fibrosis. The book also focuses on the role good nutrition and exercise play in growing and keeping one healthy. This book may be an encouragement to young readers who have special needs because it shows children with special needs leading full, exciting and rewarding lives.