A novel pathogenic variant of ATP-binding cassette subfamily B member 4 causing gallstones in a young adult.

The low phospholipid-associated cholelithiasis (LPAC) syndrome was reported in European adults with cholelithiasis and a mutation of the ATP-binding cassette subfamily B member 4 (ABCB4). The ABCB4 encodes multidrug resistance 3, which is a phospholipid translocator. Reduced phospholipid transport can lead to the formation of biliary cholesterol stones. Here, we describe a 31-year-old Japanese man diagnosed with recurrent biliary colic. Although he recovered quickly after endoscopic treatment for the most recent presentation, he had a family history of similar problems. His mother had required endoscopic treatment for choledocholithiasis and his maternal aunt had died at age 29 years because of liver failure (etiology unknown). We, therefore, performed genetic analysis, which revealed a heterozygous ABCB4C717S. LPAC syndrome was diagnosed and the patient has received ursodeoxycholic acid for 2 years with no recurrence. The same variant was identified in the patient's mother, who was subsequently found to have a left intrahepatic calculus requiring left-sided lobectomy. She has received ursodeoxycholic acid for 1 year with no recurrence. ABCB4C717S is a novel pathogenic variant, and this is the first patient diagnosed with LPAC syndrome in Japan. We should consider LPAC syndrome in young adults with recurrent cholesterol gallstones to ensure early therapy.

Episodic Syndromes That May Be Associated With Migraine: A.K.A. "the Childhood Periodic Syndromes".

Previously called "childhood periodic syndromes that are commonly precursors of migraine" in International Headache Classification of Headache Disorders (ICHD)-II, these disorders were renamed "episodic syndromes that may be associated with migraine" in ICHD-III beta. The specific disorders reviewed in this article include: benign paroxysmal torticollis, benign paroxysmal vertigo, abdominal migraine, and cyclical vomiting syndrome, as well as infantile colic, which was recently added under the appendix section in ICHD-III beta.

Heap of stones: an unusual cause for biliary colic and elevated liver function tests.

A 40-year old woman presented with symptomatic intrahepatic gallstones in one liver segment only four years after cholecystectomy for cholelithiasis. Multiple small, yellow and round calculi were completely removed from the intrahepatic bile ducts via ERCP. The young age of the patient, recurrence of gallstones after cholecystectomy and intrahepatic gallstones suggested a subtype of the low-phospholipid associated cholelithiasis syndrome, a monogenic form of cholesterol cholelithiasis due to variations of the ABCB4 gene that encodes the canalicular phospholipid transporter MDR3.

Intestinal microbiota of infants with colic: development and specific signatures.

OBJECTIVES: To provide a comprehensive analysis of the fecal microbiota in infants with colic, as compared with control infants, during their first 100 days of life. METHODS: Microbial DNA of >200 samples from 12 infants with colic and 12 age-matched control infants was extracted and hybridized to a phylogenetic microarray. RESULTS: Microbiota diversity gradually increased after birth only in the control group; moreover, in the first weeks, the diversity of the colic group was significantly lower than that of the control group. The stability of the successive samples also appeared to be significantly lower in the infants with colic for the first weeks. Further analyses revealed which bacterial groups were responsible for colic-related differences in microbiota at age 1 or 2 weeks, the earliest ages with significant differences. Proteobacteria were significantly increased in infants with colic compared with control infants, with a relative abundance that was more than twofold. In contrast, bifidobacteria and lactobacilli were significantly reduced in infants with colic. Moreover, the colic phenotype correlated positively with specific groups of proteobacteria, including bacteria related to Escherichia, Klebsiella, Serratia, Vibrio, Yersinia, and Pseudomonas, but negatively with bacteria belonging to the Bacteroidetes and Firmicutes phyla, the latter of which includes some lactobacilli and canonical groups known to produce butyrate and lactate. CONCLUSIONS: The results indicate the presence of microbial signatures in the first weeks of life in infants who later develop colic. These microbial signatures may be used to understand the excessive crying. The results offer opportunities for early diagnostics as well as for developing specific therapies.

Before the headache: infant colic as an early life expression of migraine.

OBJECTIVE: Childhood periodic syndromes are thought to be early life expressions of the genetic tendency for migraine. The objective of this study was to determine whether maternal migraine is associated with an increased risk of infant colic, because this may indicate that colic is a childhood periodic syndrome. METHODS: This was a cross-sectional study performed in general pediatric clinics. To minimize recall bias, mothers were surveyed at their infants' 2-month-old well-child visit, the age when colic is most prevalent. Colic was ascertained via parental report using modified Wessel criteria. Migraine history was obtained by having a physician diagnosis or a positive screen on ID Migraine. The primary outcome measure was difference in colic prevalence in infants with and without a maternal history of migraine. RESULTS: Data from 154 infant-mother pairs were analyzed. Infants with a maternal history of migraine were 2.6 times as likely to have colic as infants without a maternal history of migraine (29% vs 11%, prevalence ratio 2.6 (95% confidence interval 1.2-5.5), p = 0.02). There was no difference in the accuracy with which migraineur mothers perceived their infants' colic status compared with that of nonmigraineur mothers. Data on paternal history of migraine were available for 93 infants. Infants with a paternal history of migraine may have a higher prevalence of colic (22% vs 10%), although the prevalence ratio 2.3 (0.6-9.4, p = 0.24) had wide confidence intervals. CONCLUSIONS: Maternal migraine is associated with increased risk of infant colic. Because migraine has a strong genetic underpinning, this association suggests that colic may be an early life manifestation of migraine.

Expression of inflammation-associated genes in circulating leukocytes collected from horses with gastrointestinal tract disease.

OBJECTIVE: To investigate whether expression of inflammation-associated genes in leukocytes from horses with gastrointestinal tract (GIT) diseases correlated with the type of disease and outcome. ANIMALS: 10 healthy horses and 50 horses with GIT disease. PROCEDURES: A blood sample was collected from each healthy horse or horse with GIT disease (during admission to the hospital). Leukocytes were isolated, diluted to a standard concentration, and frozen until RNA extraction. Expression of 14 genes associated with inflammation was quantified by use of a real-time quantitative reverse transcription PCR assay. Results were grouped by GIT disease type and disease outcome for comparison. RESULTS: Horses with GIT disease had colic of unknown etiology (n = 8 horses), GIT inflammation or strangulation (19), or nonstrangulating GIT obstruction (23). Among the 45 horses receiving treatment, 38 were discharged from the hospital, and 7 died or were euthanized. Compared with healthy horses, horses with colic of unknown etiology had similar gene expression. Significant differences in expression of the interleukin-8, leukocyte-selectin molecule, matrix metalloproteinase-9, platelet-selectin molecule, mitochondrial superoxide dismutase, Toll-like receptor 4, and tumor necrosis factor-A genes were detected between healthy horses and horses with GIT disease. Significant differences in expression of the interleukin-1 receptor antagonist, interleukin-8, leukocyte-selectin molecule, matrix metalloproteinase-9, platelet-selectin molecule, mitochondrial superoxide dismutase, Toll-like receptor 4, and tumor necrosis factor-A genes were detected among healthy horses and horses grouped by disease outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Inflammatory gene expression in leukocytes of horses with GIT disease appeared to be related to disease pathogenesis and prognosis.

The significance of pregnancy, delivery and postpartum factors for the development of infantile colic.

Infantile colic (IC) is a distressing condition with an unclear etiology. A prospective trial was undertaken to study the hypothesis that medication during labor increases the risk of IC. Of 365 singleton deliveries, 70 (19%) developed IC. The factors associated with a significantly increased occurrence of IC were: a "psychological" complication of pregnancy, a sibling with a history of IC, a bad subjective experience of pregnancy and second parity. No significant association to "true" obstetrical complications or labor occurrences (breech, vacuum extractor, cesarean section, shoulder dystocia, pudendal block, epidural analgesia, general anesthesia or intravenous Syntocinon) was found. Modern management of labor does not increase the risk of IC. Prevention of IC is therefore achieved by psychological support to the pregnant women in the risk groups, and not by depriving her of necessary obstetrical management or pain relief.

Multiple exercise-related mononeuropathy with abdominal colic.

Hereditary neuropathy with liability to pressure palsies (NLPP) is a rare disease characterized by recurrent sensory-motor deficits precipitated by exposure to minor pressure. This report describes a variant of this neuropathy in 5 siblings suffering from painful palsies after strenuous work with concurrent episodes of abdominal colic resembling that of acute intermittent porphyria. Electrophysiological studies of the index case showed the typical abnormalities of motor and sensory nerve conduction, including clinically non-affected nerves. Light and electron-microscopic examination showed the characteristic lesions of the NLPP with sausage-like swelling of the myelin sheaths. In addition, non-compacted, "loose" myelin lamellae were frequently observed in association with distended Schmidt-Lantermann incisures. Non-compacted myelin was a prominent finding in this type of demyelinating neuropathy. We suggest that an unknown metabolic factor may induce both demyelination of peripheral nerve fibers and functional disturbance in autonomic nerves leading to attacks of abdominal pain.