Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms.

Inherited metabolic disorders presenting with gastrointestinal (GI) symptoms are characterized by the dysfunction of the esophagus, stomach, small and large intestines, and pancreas. We have summarized associations of signs and symptoms in 339 inherited metabolic diseases presenting with GI symptoms. Feeding difficulties represent the most common abnormality reported for IMDs with GI involvement (37%) followed by intestinal problems (30%), vomiting (22%), stomach and pancreas involvement (8% each), and esophagus involvement (4%).

Complex patterns of inheritance, including synergistic heterozygosity, in inborn errors of metabolism: Implications for precision medicine driven diagnosis and treatment.

Inborn errors of metabolism have traditionally been viewed as the quintessential single gene disorders; defects in one gene leads to loss of activity of one enzyme causing a metabolic imbalance and clinical disease. However, reality has never been quite that simple, and the classic "one gene-one enzyme" paradigm has been upended in many ways. Multiple gene defects can lead to the same biochemical phenotype, often with different clinical symptoms.

Inborn Errors of Metabolism and the Gastrointestinal Tract.

Inborn errors of metabolism (IEMs) are usually recognized by characteristic neurologic and metabolic manifestations and sometimes by dysmorphism. However, IEMs can present with a wide variety of gastrointestinal manifestations, whether as the primary or a minor clinical symptom. Regardless, gastrointestinal and hepatic manifestations of IEMs are important clinical features that can help identify an underlying defect; these disorders should be taken into consideration as part of a patient's clinical assessment.

Laboratory diagnostic approaches in metabolic disorders.

The diagnosis of inborn errors of metabolism (IEM) takes many forms. Due to the implementation and advances in newborn screening (NBS), the diagnosis of many IEM has become relatively easy utilizing laboratory biomarkers. For the majority of IEM, early diagnosis prevents the onset of severe clinical symptoms, thus reducing morbidity and mortality.

Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma.

Unlabelled: It has been shown that the heparin-degrading endosulfatase, sulfatase 1 (SULF1), functions as a liver tumor suppressor, but the role of the related sulfatase, sulfatase 2 (SULF2), in liver carcinogenesis remains to be elucidated. We investigated the effect of SULF2 on liver tumorigenesis. Expression of SULF2 was increased in 79 (57%) of 139 hepatocellular carcinomas (HCCs) and 8 (73%) of 11 HCC cell lines.

Detection of hepatitis C virus RNA in formalin-fixed paraffin-embedded sections with digoxigenin-labeled cRNA probes.

Although recent studies have analyzed Hepatitis C (HCV) infections in liver tissue by in situ hybridization (ISH), many of these studies have been of limited diagnostic utility because of the low copy numbers of HCV in formalin-fixed paraffin-embedded (FFPE) tissue and failure to correlate the ISH analysis with other methods of detecting HCV. Thirty six cases of liver biopsies from patients with known HCV antibody status including 20 cases of serum HCV positive and 16 cases of serum HCV negative were analyzed. All cases showed histologic features suggestion of HCV infection.