Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kabuki syndrome (KS) is associated with multiple organ system involvement. Characteristic features include long palpebral fissures with everted lower lids, prominent ears, skeletal abnormalities, mental retardation, and short stature. An increased incidence of infection has been reported in KS, and a few patients have been noted to have immune defects. However, the frequency and severity of the immune deficiency has not been clearly defined. Immunologic evaluation of 19 consecutive individuals with KS was performed at The Children's Hospital of Philadelphia. Decreased IgA levels were noted in 15/19 individuals (79%), 2 of whom had undetectable levels. Eight patients (42%) also had low total IgG levels. Specific IgG subclass abnormalities were found in 6 of 13 patients evaluated. IgM levels were less frequently decreased. One patient failed to generate anti-tetanus antibodies despite immunization. This study suggests that hypogammaglobulinemia is a frequent finding in children with KS. The pattern of antibody abnormalities seen in children with KS resembles common variable immune deficiency (CVID). Due to this increased susceptibility to infection, children with KS should have immunologic evaluations at the time of diagnosis in order to reduce preventable morbidity and mortality.
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PMID:Immune abnormalities are a frequent manifestation of Kabuki syndrome. 1588 82

We report a unique combination of symptoms in a case of Kabuki syndrome (KS), a multiple malformation/mental retardation syndrome that has a prevalence of 1:32,000 to 1:86,000. The patient was a mentally delayed 12-year-old male with trichrome vitiligo, ectodermal defect, and hypogammaglobulinemia A and G. This unique combination of signs, described here for the first time, indicates that KS comprises multiple deficits that affect not only the brain, but ectoderm-derived structures and the immune system as well. Our report may provide important clues for understanding the pathogenesis of the KS.
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PMID:Kabuki syndrome with trichrome vitiligo, ectodermal defect and hypogammaglobulinemia A and G. 1717 51

Multiple cases with various types of pediatric malabsorption syndromes were evaluated. The clinical manifestations, laboratory findings, pathophysiology, and histopathological descriptions of each patient were analyzed in an effort to clear the pathogenesis of the malabsorption syndromes and the treatments were undertaken. The cases studied, included one patient with cystic fibrosis, two with lactose intolerance with lactosuria (Durand type), one with primary intestinal lymphangiectasia, two with familial hypobetalipoproteinemia, one with Hartnup disease, one with congenital chroride diarrhea, one with acrodermatitis enteropathica, one with intestinal nodular lymphoid hyperplasia (NLH), five with intractable diarrhea of early infancy and four with glycogenosis type Ia. Each case description and outcome is described below: 1. A 15-year-old Japanese boy with cystic fibrosis presented with severe symptoms, including pancreatic insufficiency, bronchiectasis, pneumothorax and hemoptysis. His prognosis was poor. Analysis of the CFTR genes of this patient revealed a homozygous large deletion from intron 16 to 17b. 2. In the sibling case of Durand type lactose intolerance, the subjects'disaccaridase activity of the small bowel, including lactase, were within normal limits. The results of per oral and per intraduodenal lactose tolerance tests confirmed lactosuria in both. These observations suggested, not only an abnormal gastric condition, but also duodenal and intestinal mucosal abnormal permeability of lactose. 3. In the case of primary intestinal lymphangiectasia, the subject had a lymphedematous right arm and hand, a grossly coarsened mucosal pattern of the upper gastrointestinal tract (identified via radiologic examination) and the presence of lymphangiectasia (confirmed via duodenal mucosal biopsy). The major laboratory findings were hypoalbuminemia, decreased immunoglobulin levels and lymphopenia resulting from loss of lymph fluid and protein into the gastro-intestinal tract. 4. In two cases of heterozygous familial hypobetalipoproteinemia, serum total cholesterol and betalipoprotein levels were very low. The subjects presented with symptoms and signs of acanthocytosis and fat malabsorption. Further, one subject had neurological abnormalities such as mental retardation and severe convulsions. Treatment with MCT formula diet corrected the lipid malabsorption. 5. A 5-year-old girl presented with pellagra-like rashes, mental retardation and cerebellar ataxia. An oral tryptophan (Trp) and dipeptide (Trp-Phe) loading test were conducted and the renal clearance of amino acids was also evaluated in this patient and in controls. Following the oral Trp loading test, plasma levels of Trp indicated a lower peak in the case, reaching a maximum at 60 minutes. On the other hand, the oral dipeptide (Trp-Phe) loading test in the Hartnup patient showed the peak Trp plasma level was the same as the control subjects. The renal clearance of neutral amino acids in this case increased to levels 5 to 35 times normal. 6. In the case of congenital chloride diarrhea, the subject had secondary lactose intolerance, dehydration, hyponatremia, hypokalemia, hypochloremia, hyperreninemia and metabolic alkalosis. The chloride content of her fecal fluid was very high. The concentrations were 89-103 mEq/l. In contrast, her urine was chloride-free. The subject's growth and development improved after treatment with lactose free formura and oral replacement of the fecal loses of water, NaCl and KCl. Unfortunately, the patient died of a small bowel intussusception. The kidney histopathological finding was juxtaglomerular hyperplasia by a necropsy. 7. In the case of acrodermatitis enteropathica, the subject had characteristic skin lesions, low serum zinc levels and ALPase activity. An oral ZnSO4 loading test and intestinal mucosal histology by a peroral biopsy were conducted. The serum zinc peak level was 2 hours after the oral ZnSO4 loading test. Infant formula alone could not maintain normal serum zinc ranges. Light microscopic studies of the intestinal villous architecture showed a normal pattern. However, ultrastructual examination of several epithelial cells revealed numerous intracellular vesicles. After zinc therapy, these changes were decreased. The lesions were postulated as the secondary result of zinc deficiency. 8. A 12-year-old girl presented with hypogammaglobulinemia, recurrent infections, chronic diarrhea and intestinal NLH. A barium meal and follow-through examination showed multiple nodules throughout the stomach and intestine. The nodules, all uniform in size, were 2 mm diameter. The barium enema did not show NLH in the colon. Mucosal biopsy of the stomach and jejunum revealed the typical histology of NLH in the lamina propria. Also, achlorhydria was present in this patient and her serum gastrin levels were very high; 315-775 pg/ml. 9. In 4 cases of intractable diarrhea in early infancy (by Avery G B), a jejunal biopsy showed shortening villi and nonspecific enterocolitis. Some patients were found with only low lactase or low lactase and sucrase levels. An electron microscope analysis of the small bowel in 2 cases showed alterations: increased pinocytosis in microvillus membranes and lysosomes by endocytosis of undigested macromolecular substances. I postulated that the stated evidence was causative of this clinical profile. 10. I frequently observed diarrhea as a clinical manifestation in glycogenosis type Ia and lipid malabsorption in one case. The light and electron photomicrographs showed intestinal absorption cells with the glycogen deposits in the inferior devision of nuclei.
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PMID:[Clinical studies of pediatric malabsorption syndromes]. 1722 86

We describe the case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, and mental retardation who presented at an early age with colorectal cancer and multifocal anaplastic astrocytoma. He was found to have a possible germline mutation of the PMS2 gene, as evidenced by absent protein expression in both normal and tumor tissues. His parents were found to be carriers of a nonsense mutation of the PMS2 gene.
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PMID:Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation. 1799 36

We describe a 14-year-old boy with congenital bilateral cataracts, blepharophimosis, ptosis, choanal atresia, sensorineural hearing loss, short, webbed neck, poor esophageal motility, severe growth and mental retardation, skeletal anomalies, seizures, and no speech. As an infant, he had transient hypogammaglobulinemia requiring IVIG therapy. Cytogenetic studies show an apparently de novo visible duplication at 1p36.3. Fluorescence in situ hybridization (FISH) studies confirm that the common region for the 1p36 deletion syndrome (p58) is duplicated. Probes for D1Z2 at 1p36.3 and the subtelomeric region of 1p (TEL1p) are also duplicated. Array comparative genomic hybridization (aCGH) studies were done at three separate laboratories, each with somewhat different results. BAC whole genome array CGH suggests a single clone gain at the 1p terminus and a single clone deletion at 1p36.3. A targeted BAC array panel with higher resolution at the distal 1p36 region detects a telomeric duplication and an interstitial deletion. Oligonucleotide whole genomic aCGH shows the highest resolution and a more complex rearrangement: two duplications, an interstitial deletion, and a normal region. The MMP23A/B "matrix metalloproteinase 23A/B" genes are within the distal duplication region in our patient, and this patient does not have craniosynostosis. This is the first association of congenital cataracts, choanal atresia, and transient immune abnormalities with 1p36 duplication/deletion. This case illustrates the limitations of different cytogenetic technologies, and shows how three separate aCGH platforms allow for refined delineation and interpretation of the complex cytogenetic rearrangement which would not have been discovered by standard high-resolution chromosome analysis.
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PMID:Cytogenetic and array CGH characterization of de novo 1p36 duplications and deletion in a patient with congenital cataracts, hearing loss, choanal atresia, and mental retardation. 1892 66

An 8-month-old boy was admitted to the hospital because of recurrent bronchopneumonia and gastrointestinal tract infections. On physical examination, he had hypotonia, mental retardation, microcephaly with flat facies, low nasal bridge, small nose, small ears. Laboratory evaluation revealed Down syndrome, lymphopenia, hypogammaglobulinemia, reduced proportions of the peripheral blood lymphocytes with an inverted CD4/CD8 ratio and markedly reduced mitogen response of the lymphocytes. We report here unique case of Down syndrome associated with severe combined immunodeficiency.
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PMID:Down syndrome associated with severe combined immunodeficiency: a case report. 1985 34

First described in Japanese patients, Kabuki syndrome (KS) is a congenital condition associated with multiple anomalies and mental retardation. Although urological and immune abnormalities are common in KS, immune complex nephritis such as membranoproliferative glomerulonephritis (MPGN) has not yet been reported. We describe the first reported case of a KS patient with common variable immunodeficiency (CVI) and recurrent otitis media who developed severe proteinuria and hematuria due to MPGN Type 3 detected during the school urinary screening program in Japan. The patient was intravenously treated with methylprednisolone pulses followed by alternate-day prednisolone and an angiotensin receptor blocker. The patient showed remarkable improvement in both histological and urinary analyses. This case report suggests that immune abnormalities associated with KS can play an important role in the development of MPGN. Urinalysis should be regularly performed in KS patients with hypogammaglobulinemia and/or recurrent infection.
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PMID:Membranoproliferative glomerulonephritis Type 3 associated with Kabuki syndrome. 2314 49

Jacobsen syndrome is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. The typical clinical manifestations include physical growth retardation, mental retardation,facial dysmorphisms, congenital heart disease, thrombocytopenia, or pancytopenia. A Thai-Australian girl was born with multiple abnormalities. Typical features and her karyotype, 46, XX, del(ll) (q23-qter), confirmed Jacobson syndrome. She had many uncommon findings including upslanting palpebral fissures, tortuousity of retinal vessels and hypogammaglobulinemia. In addition, this case also presented with protein C deficiency, which has not been reported previously in Jacobsen syndrome. The patient was treated with phototherapy, intravenous antibiotic injection, and platelet transfusion in neonatal period. Cranioplasty was performed for prevention of the increased intracranial pressure at three months of age. Surgical correction for strabismus was in the treatment plan.
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PMID:Hypoimmunoglobulinemia and protein C deficiency in a girl with Jacobsen syndrome: a case report. 2431 61

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative.
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PMID:Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature. 3071 30