Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review describes the transmission, clinical picture and immunological abnormalities of HIV infection in children in general, and the special problems of AIDS in African children. The review begins with a thorough introduction to the epidemiology of AIDS. Transmission to children generally involves vertical transmission by placental transfer or transmission of HIV via transfusion of blood and blood products, or by contaminated needles. Casual transfer is unknown, and only a few cases of transmission via breast milk are known. The clinical picture of HIV infection in infants and children differs from that in adults in 3 important aspects: earlier onset, different clinical presentation and existence of AIDS embryopathy. The average onset was 5 months of age. The most common symptoms in young children are chronic interstitial pneumonitis without demonstrable etiology, hepatomegaly, failure to thrive, adenopathy, diarrhea, oral or perineal thrush, eczema and thrombocytopenia. The common opportunistic infections are pneumocystis carinii pneumonia, cytomegalovirus, Epstein-Barr virus, Cryptosporidium diarrhea, pyogenic infections of the middle ear and gram-negative septicemia. Several infections seen in adult AIDS cases are rare in children: mycobacterium avium-intracellulare, toxoplasma gondii, hepatitis B, as well as Kaposi's sarcoma, malignant lymphoma and cardiac abnormalities. The AIDS embryopathy or HIV dysmorphic syndrome is characterized by immunological abnormalities, growth failure, and craniofacial dysmorphism, particularly microcephaly, prominent box-like forehead, hypertelorism, flattened nasal bridge, obliquity of the eyes, blue sclerae and patulous lips. AIDS in African children is extremely difficult to diagnose because of similarities between the presenting symptoms and those commonly seen in sick children there, many of whom are also immune compromised. Where serotesting is available, the picture is complicated by cross reaction between the test agents and some factor found in sera from malaria patients. Seropositivity in some areas is high, increased by the prevalence of transfusion and injection treatments. Diagnosis is made more difficult by lack of laboratory facilities and difficulties in follow-up for pediatric patients. The CDC definitions of AIDS and ARC, and the WHO/CDC definitions of AIDS are appended.
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PMID:Human immunodeficiency virus infection in childhood. 245 15

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the lysosomal hydrolase a-L-Iduronidase leading to accumulation of the GAGs, dermatan sulfate, and heparan sulphate, The disease spectrum includes a disorder with severe involvement and CNS disease Hurler disease (HPS I H) a chronic disease without CNS disease Scheie disease (HPS I S5) and the intermediate Hurler/Scheie disease(HPS I HIS).The urine GAGs pattern. confirmed by Iduronidase enzyme assay is diagnostic. Over 200 mutations exist. Genotype / phenotype correlation is poor but two nonsense mutations results in Hurler disease.The skeletal disease dysostosis multiplex (DM) is seen in severe variants of MPS I. The hypoplastic odontoid putting these patients at high risk of cervical cord damage. MPS IH (Hurler Disease) affected infants develop a spinal 'gibbus' deformity, persistent nasal discharge, middle ear effusions and frequent upper respiratory infection. They have "coarse", facial features, and an enlarged tongue. . Progressive upper airway disease leads to obstructive sleep apnoea. Corneal clouding and cognitive impairment appears, growth ceases. Joint stiffness and contractures limit mobility. Cardiac disease is universal. Death occurs before 10 years. SCHEIE patients are diagnosed as teenagers with hepatomegaly, joint contractures, cardiac valve abnormalities and corneal clouding . Prolonged survival with considerable disability without cognitive impairment is usual. MPS IH/S Hurler/Scheie. is diagnosed by 6.5 years, with variable skeletal and visceral manifestations without cognitive involvement. Joint stiffness, corneal clouding, , umbilical hernia, abnormal facies, hepatomegaly, joint contractures, and cervical myelopathy occur. Patients die in their 20s .Haematopoietic stem cell transplantation (HSCT) the standard treatment of MPS IH for 30 years is unpredictable .When performed before 2 years it can stabilize cognitive impairment. Hepatosplenomegaly, urine GAGs excretion, upper airways obstruction and cardiomyopathy improve . The coarse hair and facial features soften and corneas partly clear,but dysostosis multiplex and cervical instability are not improved. Enzyme replacement therapy (ERT) in patients with MPS IH is associated with improved GAG excretion, left ventricular hypertrophy,sleep studies and liver size. The standard treatment of MPS IHIS and MIPS IS is ERT a-L-Iduronidase, laronidase, a life-long therapy. GAG excretion is reduced, respiratory function and physical endurance improve. Joint mobility improves but not dural thickening, cardiac valve lesions or eye changes. MPS I mice have been successfully treated with IDUA-expressing mesenchymaf stem cells . Gene therapy may be developed for MPS I, via an ex vivo approach demonstrated to improve even skeletal outcomes in animal models.
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PMID:Mucopolysaccharidosis type I. 2534 91