Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.
Pain Insensitivity, Congenital

The objective of this study was to analyze the three different management modalities for isolated superior mesenteric artery (SMA) dissection. We did a comprehensive literature search and found 703 articles on the initial search, out of which 111 articles consisting of 145 patients were selected for analysis. The mean age was 55.7 years (standard deviation,9.7;33–85) and 80.6% were male. These patients were managed conservatively (41.3%), endovascularly (28.1%) or surgically (30%). The median follow-up was 10 months (interquartile range [IQR], 4–18 months), 12 months (IQR, 6–19 months) and 14 months (IQR, 6–20 months) respectively. Contrast-enhanced computed tomography (CT) was the most commonly used diagnostic tool in the conservative group (43.8%), while conventional CT scan was the most widely used in endovascular (58.1%) and surgical group (50%). 17% percent of the conservative group had SMA angiography for diagnosis, while this was less than 3% in the other groups. Of these patients, 96.7%, 97.4%, and 100.0% recovered successfully in the conservative, endovascular, and surgical groups respectively. There was no significant difference in the mortality between the three groups (Pearson χ²=0.482). This suggests a conservative and endovascular approach could be used in most patients, which can reduce costs and surgery-related morbidity and mortality. Surgical management should be reserved for cases having infarction or widespread bowel ischemia and in cases where other treatment modalities fail.
Angiography ; Diagnosis ; Follow-Up Studies ; Humans ; Infarction ; Ischemia ; Male ; Mesenteric Artery, Superior ; Mortality ; Tomography, X-Ray Computed

The objective of this study was to analyze the three different management modalities for isolated superior mesenteric artery (SMA) dissection. We did a comprehensive literature search and found 703 articles on the initial search, out of which 111 articles consisting of 145 patients were selected for analysis. The mean age was 55.7 years (standard deviation,9.7;33–85) and 80.6% were male. These patients were managed conservatively (41.3%), endovascularly (28.1%) or surgically (30%). The median follow-up was 10 months (interquartile range [IQR], 4–18 months), 12 months (IQR, 6–19 months) and 14 months (IQR, 6–20 months) respectively. Contrast-enhanced computed tomography (CT) was the most commonly used diagnostic tool in the conservative group (43.8%), while conventional CT scan was the most widely used in endovascular (58.1%) and surgical group (50%). 17% percent of the conservative group had SMA angiography for diagnosis, while this was less than 3% in the other groups. Of these patients, 96.7%, 97.4%, and 100.0% recovered successfully in the conservative, endovascular, and surgical groups respectively. There was no significant difference in the mortality between the three groups (Pearson χ²=0.482). This suggests a conservative and endovascular approach could be used in most patients, which can reduce costs and surgery-related morbidity and mortality. Surgical management should be reserved for cases having infarction or widespread bowel ischemia and in cases where other treatment modalities fail.