Hereditary chronic pancreatitis

Abstract

Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds

“…For example, because X-chromosome inactivation is complete in most ectodermal and mesodermal tissues by 9.5 dpc (Tan et al, 1993; Tam et al, 1994) there is a possibility that NC cells, at an earlier embryonic stage, migrate into and reside in the epithelium of the tongue primordium, and then proliferate and differentiate in taste papilla residences that will include taste buds. In humans, an absence or reduction of taste papillae has been found in several neurologic disorders (Axelrod and Gold-von Simson, 2007; Gardiner et al, 2008; Rubin and Anderson, 2008) that affect the development and maintenance of sensory and autonomic neurons which in general have a neurogenic origin from both ectodermal placode and neural crest. In one of these neuropathies, familial dysautonomia, absolute absence of fungiform and vallate taste papillae (Smith et al, 1965a, b) suggests a causal link with NC defects.…”

Hypoplastic Left Heart Syndrome Sequencing Reveals a Novel NOTCH1 Mutation in a Family with Single Ventricle Defects

“…In HLHS, the left ventricle (LV) is severely underdeveloped, forming a vestigial chamber. HLHS is uniformly fatal without multi-stage palliative surgeries or cardiac transplantation [2,3]. …”

Successful transfer from insulin to oral sulfonylurea in a 3-year-old girl with a mutation in the KCNJ11 gene

“…NDM can present as permanent neonatal diabetes (PNDM) or transient neonatal diabetes mellitus (TNDM) that can sometimes be differentiated clinically. Molecular genetic analysis can dramatically differentiate between the two subtypes from the onset of the disease 2. The common causes of PNDM are activating mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the K ATP sensitive channel of the pancreatic β-cell 2.…”

“…Molecular genetic analysis can dramatically differentiate between the two subtypes from the onset of the disease 2. The common causes of PNDM are activating mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the K ATP sensitive channel of the pancreatic β-cell 2. Mutations in KCNJ11 cause PNDM in about 53% of the cases 3.…”