Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 7-year-old boy presented with bilateral ptosis and atypical retinitis pigmentosa. Before age two, he had had an Fe-refractory anemia, with neutropenia and thrombopenia. Just prior to the ophthalmic examination, the patient developed lactate acidosis, muscular hypotonia, ataxia and increased protein in the spinal fluid. Pancytopenia, pancreas dysfunction and growth retardation are the main features of Pearson's syndrome, most children not surviving beyond age three. The cause of Pearson's syndrome in our patient turned out to be a 5 kb deletion in the mitochondrial DNA. Similar deletions have been described in the Kearns-Sayre syndrome. It seems that children who survive the initial phase of Pearson's syndrome, may develop Kearns-Sayre syndrome.
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PMID:Kearns-Sayre's syndrome developing in a boy who survived pearson's syndrome caused by mitochondrial DNA deletion. 130 30

The clinical and morphologic findings of three patients with metabolic acidosis, methylmalonic aciduria, and homocystinuria are presented. The clinical evolution of the patients was similar and was characterized in the first weeks of life by failure to thrive, hypotonia, and lethargy associated with pancytopenia and hepatic dysfunction, eventually progressing to severe respiratory insufficiency and renal failure consistent with a hemolytic-uremic syndrome. The patients died at 40, 45, and 75 days of age. Biochemical analyses and complementation studies revealed a congenital anomaly of vitamin B12 metabolism (cobalamin C disease). Postmortem morphologic findings in all three cases were dominated by a thrombotic microangiopathy of the kidneys and lungs, diffuse hepatic steatosis, and megaloblastic changes in the bone marrow. A severe gastritis with striking cystic dysplastic mucosal changes and total absence of parietal and chief cells was a consistent finding in all three cases, the rest of the gastrointestinal tract appearing essentially normal. Cobalamin C disease is an intracellular defect of cobalamin metabolism with possible recessive inheritance that can result in multiorgan failure early in life, with a thrombotic microangiopathy and unusual changes in the gastric mucosa.
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PMID:A congenital anomaly of vitamin B12 metabolism: a study of three cases. 156 46

A 9-month-old Turkish boy was diagnosed as having Griscelli disease (Chediak-Higashi-like syndrome). Clinical signs consisted of silver-grey hair and a relatively light skin colour, recurrent episodes of fever, with or without detectable infections, increasing hepatosplenomegaly, hypotonia and motor retardation. Laboratory studies showed pancytopenia of varying degree but neither inclusion bodies nor vacuoles were seen in his leucocytes. Serum immunoglobulin levels were normal except for a IgG2 deficiency. In the mixed lymphocyte reaction the stimulation capacity of the leucocytes was decreased. Microscopic examination of his hair and electron-microscopic examination of a skin biopsy further confirmed the diagnosis. Shortly before the diagnosis was made, the child developed cerebral symptoms with hemiparesis and convulsions. A CT scan suggested cell infiltration of the brain. A few weeks later the boy died of an infection.
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PMID:Griscelli disease with cerebral involvement. 182 34

Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. Early diagnosis and institution of therapy may be effective in improving survival and quality of life.
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PMID:Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period. 1197 7

We report on two cases of distal monosomy 11q and partial trisomy 16q due to a familial subtle translocation detected by FISH subtelomere screening. Exact breakpoint analyses by FISH with panels of BAC probes demonstrated a 9.3-9.5 megabase partial monosomy of 11q24.2-qter and a 4.9-5.4 megabase partial trisomy of 16q24.1-qter. The index patient displayed craniofacial dysmorphisms, mild mental retardation and postnatal growth retardation, muscular hypotonia, mild periventricular leukodystrophy, patent ductus arteriosus, thrombocytopenia, recurrent infections, inguinal hernia, cryptorchidism, pes equinovarus, and hearing deficiencies. In his mother's cousin who bears the identical unbalanced translocation, mild mental retardation, patent ductus arteriosus, hypogammaglobulinemia, recurrent infections, unilateral kidney hypoplasia, pes equinovarus, and hearing deficiencies were reported. Since only four descriptions of cryptic or subtle partial trisomies 16q have been published to date, our patients contribute greatly to the delineation of the phenotype of this genomic imbalance. In contrast to this, terminal deletions of the long arm of chromosome 11 cause a haploinsufficiency disorder (Jacobsen syndrome) in which karyotype-phenotype correlations are already being established. Here, our findings contribute to the refinement of a phenotype map for several Jacobsen syndrome features including abnormal brain imaging, renal malformations, thrombocytopenia/pancytopenia, inguinal hernia, testicular ectopy, pes equinovarus, and hearing deficiency.
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PMID:Further delineation of the phenotype maps for partial trisomy 16q24 and Jacobsen syndrome by a subtle familial translocation t(11;16)(q24.2;q24.1). 1622 63

Objectives. To evaluate the clinical features, physical findings, diagnosis, and laboratory parameters of the patients with propionic acidaemia (PA). Methods. The records of diagnosed cases of propionic acidaemia were reviewed, retrospectively. Results. Twenty-six patients with PA had 133 admissions. The majority (85%) of the patients exhibited clinical manifestations in the 1st week of life. Regarding clinical features, lethargy, fever, poor feeding, vomiting, dehydration, muscular hypotonia, respiratory symptoms, encephalopathy, disturbance of tone and reflexes, and malnutrition were observed in 51-92% admissions. Metabolic crises, respiratory diseases, hyperammonaemia, metabolic acidosis, hypoalbuminaemia, and hypocalcaemia were observed in 30-96% admissions. Pancytopenia, ketonuria, hypoproteinemia, hypoglycaemia, and mildly disturbed liver enzymes were found in 12-41% admissions. Generalised brain oedema was detected in 17% and cerebral atrophy in 25% admissions. Gender-wise odd ratio analysis showed value of 1.9 for lethargy, 1.99 for respiratory diseases, 0.55 for anaemia, and 1.82 for hypocalcaemia. Conclusion. Propionic acidaemia usually presents with wide spectrum of clinical features and disturbances of laboratory parameters in early neonatal age. It is associated with significant complications which deteriorate the patients' quality of life. Perhaps with early diagnosis of the disease and in time intervention, these may be preventable.
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PMID:Clinical spectrum of propionic acidaemia. 2428 98

Vitamin B12 deficiency may be responsible of serious hematologic and neurodevelopmental abnormalities. We report the case of an infant who was hospitalized because of recurrent infections, failure to thrive, hypotonia, and weakness. He was 8 months old and had been exclusively breastfed. Blood cell count showed pancytopenia with megaloblastic bone marrow. The serum IgG concentration was low. Vitamin B12 level was very low and associated with increased urinary methylmalonic acid. Cobalamin deficiency was caused by mother's unrecognized pernicious anemia. Vitamin B12 supply led to rapid clinical and hematologic improvement.
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PMID:Frequent Infections, Hypotonia, and Anemia in a Breastfed Infant. 2806 Jan 11

Here we present the case of a 57-years old patient affected by hemophagocytic lymphohistiocytosis (HLH), a rare disease characterized by an uncontrolled immune activation, resulting in clinical and biochemical manifestations of extreme inflammation. In a previous hospitalization, the patient showed fever, hepato-splenomegaly, pancytopenia, hyperferrtitinemia, lymphadenopathy and cholestasis. No diagnosis was done, however, he totally recovered after splenectomy. Eight months later, he relapsed, showing also hypofibrinogenemia, hypertriglyceridemia, hemophagocytic signs in bone marrow, cholestatic jaundice, high LDH and high PT-INR. Interestingly, he presented increased levels of amylase and lipase in absence of radiologic signs of pancreatitis. He was treated with Dexamethasone and Cyclosporine according to HLH-2004 guidelines. The clinical and biochemical manifestations disappeared in a few weeks, but he was newly hospitalized for lower limbs hypotonia caused by a hemophagocytic lesion of the cauda equina and lumbar cord. The death occurred in a few days, despite the immunosuppressive treatment.
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PMID:Hemophagocytic Lymphohistiocytosis, an Unclear Nosologic Entity: Case Report of an Adult Man with Rising of Amylase and Lipase and Spinal Cord Infiltration. 2828 28

Pediatric intractable autoimmune hepatitis is rare and may be responsible for acute liver failure. Mutations in the itchy E3 ubiquitin protein ligase (ITCH) gene (located on chromosome 20q11.22) can lead to a deficiency of the encoded protein, resulting in increased T-cell activity with lack of immune tolerance and manifestation of a complex systemic autoimmune disease. A 1-year-old girl of consanguineous parents received a liver transplant (LT) because of acute liver failure attributed to a drug-induced hypereosinophilic syndrome with positive liver-kidney-mikrosome-2 antibodies. Notable findings were syndromic features, dystrophy, short stature, psychomotor retardation, and muscular hypotonia. Later, we saw corticosteroid-sensitive rejections as well as a systemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). Histologically, liver cirrhosis with lobular inflammatory infiltrates, giant-cell hepatitis, and ductopenia was verified in chronic cholestasis. Shortly after a second LT, a comparable liver histology could be detected, and viral, bacterial, and mycotic infections deteriorated the general health condition. Because of refractory pancytopenia related to portal hypertension and hypersplenism, a posttransplant lymphoproliferative disorder was excluded. One year after the second LT, epidural and subdural bleeding occurred. Three months afterward, the girl died of sepsis. Postmortem, whole-exome sequencing revealed a homozygous mutation in the ITCH gene. A biallelic mutation in ITCH can cause a severe syndromic multisystem autoimmune disease with the above phenotypic characteristics and acute liver failure because of autoimmune hepatitis. This case reveals the importance of ubiquitin pathways for regulation of the immune system.
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PMID:Mutation in ITCH Gene Can Cause Syndromic Multisystem Autoimmune Disease With Acute Liver Failure. 3070 42

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is one of the inborn errors of immunity, characterized by impaired function of the regulatory T cells. Clinical manifestations of IPEX syndrome are characterized by various autoimmune diseases with autoantibodies. The comprehensive analysis for autoantibodies using human proteome microarrays in the four patients with IPEX syndrome was performed. The numbers of the highly expressed autoantibody showing relative log2 ratios greater than 1 were 1876, 513, 234 and 831 (mean: 864), respectively. Some novel autoantibodies which could explain the phenotypes of patients, adrenal dysfunction, muscular hypotonia, afibrinogenemia, enteropathy and pancytopenia were identified. Various kinds of autoantibodies targeting testis-specific antigens were also identified. Human proteome microarray is a powerful tool to understand the pathophysiology of IPEX syndrome. The larger cohort analysis using this method will provide further understanding of the impaired immune tolerance in humans.
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PMID:Identification of autoantibodies using human proteome microarrays in patients with IPEX syndrome. 3095 39


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