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Biomedical subjects

H Mandel

Publications and source records attributed to H Mandel.

89 records · Page 5Linked to original sources
PubMed1989

Familial distal renal tubular acidosis with neurosensory deafness: early nephrocalcinosis.

Nephrocalcinosis was observed in 3 children of one family with distal renal tubular acidosis (dRTA). At presentation, all 3 patients had failure to thrive, rickets, hyperchloremic metabolic acidosis, hypokalemia, hypophosphatemia and hypercalciuria. At a later age, sensorineural hearing impairment was detected. Nephrocalcinosis was diagnosed in the index case at the age of 5 years, when a plain abdominal roentgenogram was first made; in the younger brother and sister, nephrocalcinosis was detected earlier at the age of 4 months and 5 weeks, respectively. All 3 patients required large doses of alkali (7.5-9.5 mEq/kg body weight/day) during infancy and early childhood to correct the acidosis and to prevent progression of the nephrocalcinosis. Contrary to the current notion that in children with dRTA, nephrocalcinosis is observed only after the age of 3 years, it appears that in some instances nephrocalcinosis may develop in early infancy. The occurrence of nephrocalcinosis at a very young age may be a manifestation of a severe genetically transmitted variant of dRTA and emphasizes the need for early diagnosis and optimal treatment of these patients from the first days of life.

Acidosis, Renal Tubular↗
PubMed1989

[Inborn errors of metabolism: lessons from a clinical case].

Dramatic advances in recent years in the diagnosis and treatment of inborn errors of metabolism (IEM) make it imperative for the physician to be both aware of their occurrence and acquainted with their clinical presentations. Many may present with symptoms and signs common to sick infants, such as refusal to feed, vomiting and convulsions. Failure to include IEM in the differential diagnosis may have grave consequences, because only prompt recognition and appropriate treatment of a metabolic crisis can help prevent irreversible brain damage or death. We describe a 3-week-old female infant, eventually diagnosed as having an IEM (3-hydroxy-3-methyl-glutaric aciduria), who was admitted to various hospitals and died during her last admission. We focused on the clinical and laboratory findings of each of the first 2 admissions which might have provided clues to the true nature of the illness had the clinicians been aware of the possibility of IEM. Patients with IEM are generally managed in specialized centers; however, the responsibility for initial recognition and immediate treatment of a metabolic emergency lies with the primary physician. The purpose of our case presentation and the discussion of the lessons derived from it, is to prompt the clinician to an awareness and understanding of a subject that used to be considered reserved for specialists. In fact, all that is needed is clinical alertness and the performance of certain well-focused, simple laboratory tests for IEM.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

The importance of recognizing secondary carnitine deficiency in organic acidaemias: case report in glutaric acidaemia type II.

Secondary carnitine deficiency in a patient with glutaric acidaemia type II, due to deficient ETF-dehydrogenase activity, is described. The patient responded clinically to a pharmacological dose of riboflavin and a restricted protein diet. In the second year of her life she developed more frequent and severe exacerbations during intercurrent infections from which she did not fully recover. Hypotonia and marked ataxia persisted. Plasma carnitine was entirely complexed as acylcarnitine with no free carnitine detected. Retrospective evaluation of several frozen urine specimens obtained since the age of 10 months revealed undetectable free carnitine with elevated acylcarnitine levels. Marked clinical improvement was observed following L-carnitine supplementation. The hypotonia and ataxia disappeared. The frequency and the severity of the exacerbations were noticeably decreased. The role of L-carnitine in preventing the accumulation of acyl-CoA compounds in inborn errors of organic acid metabolism is further emphasized by this patient. The necessity to evaluate free carnitine, acylcarnitine and acyl/free ratio in the assessment, follow-up and management of patients with inborn errors of organic acid metabolism is discussed.

Carnitine↗
PubMed1988

Thiamin status of the offspring of diabetic rats.

Erythrocyte transketolase activity and thiamin pyrophosphate effect were examined in the offspring of streptozotocin-diabetic rats. Thiamin reserve was found to be significantly reduced in litters of untreated diabetic rats as compared to control and to insulin-treated diabetic rats. Supplementation of the untreated diabetic dams throughout pregnancy with oral thiamin was associated with a significantly improved thiamin status of the litters. We conclude that, due to enhanced fetal glucose turnover during diabetic gestation, a fetal thiamin deficiency state may evolve; this condition can be remedied with maternal thiamin supplementation.

Animals↗
PubMed1983

Primary sclerosing cholangitis associated with immunodeficiency.

An infant, first admitted at the age of 5 months with diarrhea (which was adequately treated with formula), was readmitted at the age of 1 year with poor weight gain, steatorrhea, and hepatomegaly. Liver function test results were compatible with cholestatic jaundice, and hepatobiliary scintigraphy visualized dilated bile ducts and evidence of hepatocellular disease. Exploratory laparotomy, liver biopsy, and cholangiography disclosed pathologic and roentgenographic findings of primary sclerosing cholangitis (PSC). The patient proved to be immunodeficient, pointing to the possible pathogenetic role of immunodeficiency in causing PSC in some patients. It is important to look for the disease in immunodeficient children and in patients with ulcerative colitis, and to consider PSC in the differential diagnosis of cholestatic jaundice.

Bile Ducts↗
PubMedDate not supplied

Cardiac manifestations in thiamine-responsive megaloblastic anemia syndrome.

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is a rare autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment. Other features of this syndrome gradually develop. We describe three TRMA patients with heart rhythm abnormalities and structural cardiac anomalies. Eight other reported TRMA patients also had cardiac anomalies. Recently, the TRMA gene, SLC19A2, was identified, encoding a functional thiamine transporter. Characterization of the metabolic defect of TRMA may shed light on the role of thiamine in common cardiac abnormalities.

Adolescent↗
PubMedDate not supplied

Fludarabine-based protocol for haploidentical peripheral blood stem cell transplantation in Hurler syndrome.

To assess the feasibility of performing a haploidentical peripheral blood stem cell transplantation (PBSCT) in a child with Hurler syndrome after a novel conditioning regimen consisting of fludarabine monophosphate, anti-T-lymphocyte globulin, low-dose busulfan, and single-dose total body irradiation of 750 cGy. A 16-month old boy with Hurler syndrome underwent haploidentical PBSCT from his 3/6 HLA-matched sister. Pretransplant conditioning consisted of fludarabine (30 mg/m2 per day) from day -10 to day -5, busulfan (4 mg/kg per day) on days -7 and -6, rabbit anti-T-lymphocyte globulin (10 mg/kg per day) from day -4 to day -1, and total body irradiation of 750 cGy on day -1. In vitro T-cell depletion was carried out with rat antihuman CDw52 monoclonal antibody (Campath-1G). The fludarabine-based protocol was well-tolerated, with mild toxicity and no major transplant-related complications or graft-versus-host disease. Engraftment was complete and stable. Chimerism was 100% donor origin, as determined by restriction fragment length polymorphism. Cytogenetic and polymerase chain reaction-various number of tandem repeats (PCR-VNTR) analyses of peripheral blood and bone marrow showed 100% reconstitution with female donor cells. The patient underwent the transplant 30 months ago and is in good clinical condition, with normal counts, no signs of graft-versus-host disease, and no infectious episodes; neurologic signs have stabilized. Haploidentical PBSCT, T-cell-depleted by means of Campath-1G, may serve as a therapeutic alternative for patients with Hurler syndrome when a fully matched sibling is not available.

Adolescent↗
PubMedDate not supplied

Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C.

PURPOSE: Niemann-Pick disease type C (NP-C) is an autosomal recessive lipid storage disease manifested by an impairment in cellular cholesterol homeostasis. The clinical phenotype of NP-C is extremely variable, ranging from an acute neonatal form to an adult late-onset presentation. To facilitate phenotype-genotype studies, we have analyzed multiple Israeli NP-C families. METHODS: The severity of the disease was assessed by the age at onset, hepatic involvement, neurological deterioration, and cholesterol esterification studies. Screening of the entire NPC1 coding sequence allowed for molecular characterization and identification of disease causing mutations. RESULTS: A total of nine NP-C index cases with mainly neurovisceral involvement were characterized. We demonstrated a possible link between the severity of the clinical phenotype and the cholesterol esterification levels in fibroblast cultures following 24 hours of in vitro cholesterol loading. In addition, we identified eight novel mutations in the NPC1 gene. CONCLUSIONS: Our results further support the clinical and allelic heterogeneity of NP-C and point to possible association between the clinical and the biochemical phenotype in distinct affected Israeli families.

Age of Onset↗