Autoimmunity, and Neoplasm of the pancreas

Low match MULTIPLE ENDOCRINE NEOPLASIA TYPE 4

Multiple endocrine neoplasia type 4 (MEN4) is a very rare form of MEN (see this term), an inherited cancer syndrome, characterized by parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors.

MULTIPLE ENDOCRINE NEOPLASIA TYPE 4 Is also known as men4

• Neoplasm
• Hypertension
• Diarrhea
• Diabetes mellitus
• Hypothyroidism

SOURCES: OMIM MESH ORPHANET MENDELIAN

Low match PANCREATIC CANCER, SUSCEPTIBILITY TO, 2

PANCREATIC CANCER, SUSCEPTIBILITY TO, 2 Is also known as pnca2

• Neoplasm of the pancreas

SOURCES: OMIM MENDELIAN

Low match THIOPURINES, POOR METABOLISM OF, 1; THPM1

THPM1 is an autosomal recessive trait associated with severe hematopoietic toxicity when patients are treated with standard doses of the antineoplastic agents 6-mercaptopurine (6MP) or 6-thioguanine (6TG), or the immunosuppressant azathioprine (AZA) (Lennard et al., 1989).The thiopurines are prodrugs that require extensive metabolism in order to exert their cytotoxic action. Azathioprine is nonenzymatically reduced to 6MP. 6MP and 6TG are activated by HPRT (OMIM ) and subsequent steps to form cytotoxic thioguanine nucleotides (TGNs) which are incorporated into DNA and/or RNA, causing DNA-protein cross-links, single-strand breaks, interstrand cross-links, and sister chromatid exchange. TPMT functions mainly to inactivate these drugs; thus, a deficiency of TPMT results in increased conversion to toxic TGNs, which can result in myelosuppression (Coulthard and Hogarth, 2005). However, 6MP is unique in that it can also be converted via TPMT into a methyl-thioinosine 5-prime monophosphate (MeTIMP), a metabolite that inhibits de novo purine synthesis and likely contributes to the cytotoxic effect of 6MP (Vogt et al., 1993; Krynetski et al., 1995; Coulthard and Hogarth, 2005). Genetic Heterogeneity of Poor Thiopurine MetabolismSee also THPM2 (OMIM ), caused by variation in the NUDT15 gene (OMIM ) on chromosome 13q14.

THIOPURINES, POOR METABOLISM OF, 1; THPM1 Is also known as thiopurine s-methyltransferase deficiency|tpmt deficiency|tpmtd

• Abnormality of metabolism/homeostasis
• Autoimmunity
• Leukemia
• Pancytopenia
• Bone marrow hypocellularity

SOURCES: MESH ORPHANET OMIM MENDELIAN

Low match DIABETES MELLITUS, KETOSIS-PRONE; KPD

In addition to classic type 1 (see {222100}) and type 2 (see {125853}) diabetes mellitus, atypical presentations are seen, particularly in populations of African ancestry. Ketosis-prone diabetes, the most common atypical form, is characterized by an acute initial presentation with severe hyperglycemia and ketosis, as seen in classic type 1 diabetes, but after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies show a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic beta-cell autoimmunity is a rare finding, and association with type 1 susceptibility HLA alleles is variable (Sobngwi et al., 2002).

• Diabetes mellitus
• Weight loss
• Autoimmunity
• Type II diabetes mellitus
• Insulin resistance

SOURCES: ORPHANET OMIM MENDELIAN

Low match DIABETES MELLITUS, INSULIN-DEPENDENT; IDDM

The type of diabetes mellitus called IDDM is a disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of IDDM have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype.The classical phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.

DIABETES MELLITUS, INSULIN-DEPENDENT; IDDM Is also known as diabetes mellitus, type i|jod|juvenile-onset diabetes

• Hypertension
• Diabetes mellitus
• Autoimmunity
• Nephropathy
• Type II diabetes mellitus

SOURCES: OMIM MENDELIAN

Low match HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE I; HHC1

Familial hypocalciuric hypercalcemia (HHC) is a heritable disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. HHC is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone (PTH ) level. Hypermagnesemia is typically present. Individuals with HHC are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults (summary by Hannan et al., 2010).Characteristic features of familial hypocalciuric hypercalcemia include mild to moderate hypercalcemia, nonsuppressed parathyroid hormone, relative hypocalciuria while hypercalcemic (calcium/creatinine clearance ratio less than 0.01, or 24-hr urine calcium less than 6.25 mmol), almost 100% penetrance of hypercalcemia from birth, absence of complications, persistence of hypercalcemia following subtotal parathyroidectomy, and normal parathyroid size, weight, and histology at surgery. However, atypical presentations with severe hypercalcemia, hypercalciuria with or without nephrolithiasis or nephrocalcinosis, kindreds with affected members displaying either hypercalciuria or hypocalciuria, postoperative normocalcemia, and pancreatitis have all been described in FHH (Warner et al., 2004). Genetic Heterogeneity of Hypocalciuric HypercalcemiaFamilial hypocalciuric hypercalcemia type II (HHC2 ) is caused by mutation in the GNA11 gene (OMIM ) on chromosome 19p13, and HHC3 (OMIM ) is caused by mutation in the AP2S1 gene (OMIM ) on chromosome 19q13.

HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE I; HHC1 Is also known as hhc|familial benign hypercalcemia 1|hypercalcemia, familial benign|fhh|fbh1|fhh1

• Neoplasm
• Pain
• Fatigue
• Renal insufficiency
• Headache

SOURCES: OMIM MESH ORPHANET MENDELIAN

Low match IMMUNE DYSREGULATION-POLYENDOCRINOPATHY-ENTEROPATHY-X-LINKED SYNDROME

Immunodysregulation - polyendocrinopathy - enteropathy - X-linked (IPEX) syndrome is a severe congenital systemic autoimmune disease characterized by refractory diarrhea, endocrinopathies, cutaneous involvement, and infections.

IMMUNE DYSREGULATION-POLYENDOCRINOPATHY-ENTEROPATHY-X-LINKED SYNDROME Is also known as enteropathy, autoimmune, with hemolytic anemia and polyendocrinopathy|ipex|autoimmune enteropathy type 1|iddm-secretory diarrhea syndrome|x-linked autoimmunity-allergic dysregulation syndrome|polyendocrinopathy, immune dysfunction, and diarrhea, x-linked|

• Growth delay
• Failure to thrive
• Anemia
• Intrauterine growth retardation
• Diarrhea

SOURCES: MESH OMIM ORPHANET MENDELIAN

Low match PERMANENT NEONATAL DIABETES MELLITUS

Permanent neonatal diabetes mellitus (PNDM) is a monogenic form of neonatal diabetes (NDM, see this term) characterized by persistent hyperglycemia within the first 12 months of life in general, requiring continuous insulin treatment.

PERMANENT NEONATAL DIABETES MELLITUS Is also known as monogenic diabetes of infancy|pndm

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Ataxia
• Failure to thrive

SOURCES: ORPHANET MENDELIAN

Low match TRANSIENT NEONATAL DIABETES MELLITUS

Transient neonatal diabetes mellitus (TNDM) is a genetically heterogeneous form of neonatal diabetes (NDM, see this term) characterized by hyperglycemia presenting in the neonatal period that remits during infancy but recurs in later life in most patients.

TRANSIENT NEONATAL DIABETES MELLITUS Is also known as tndm3|tndm

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Failure to thrive

SOURCES: ORPHANET OMIM MENDELIAN