Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia

A case of a child with recurrent episodes of severe hypoglycemia since the age of 6 months is reported. Biochemical evaluation extended to the first-degree relatives is consistent with a familial form of hypoglycemia due to a leucine-sensitive hyperinsulinism. In addition, this patient has a persistent elevation of serum ammonia levels of uncertain etiology that is more pronounced after meals. Urea cycle defects, organic acidurias, and beta-oxidation defects have been ruled out, as well as a possible excessive deamination of glucogenetic amino acids. This unexpected hyperammonemia, which was also detected in the mother, might be related to leucine hypersensitivity.     

Valproic acid and secondary hyperammonemia

An 11-year-old girl with complex seizures was started on valproic acid (VPA) in addition to clonazepam and ethosuximide. Shortly thereafter, she developed marked hyperammonemia that was worsened by a protein load. The hyperammonemia improved somewhat when protein was not given, and it resolved on discontinuation of the valproic acid. No associated changes in serum transaminases or bilirubin were observed. Isolated hyperammonemia may occur soon after VPA ingestion and appears to be a relatively infrequent, reversible side effect. The mechanism of hyperammonemia probably differs from other manifestations of hepatotoxicity, such as elevated transaminases or frank hepatic failure.     

Prion protein NMR structure and familial human spongiform encephalopathies

The refined NMR structure of the mouse prion protein domain mPrP(121-231) and the recently reported NMR structure of the complete 208-residue polypeptide chain of mPrP are used to investigate the structural basis of inherited human transmissible spongiform encephalopathies. In the cellular form of mPrP no spatial clustering of mutation sites is observed that would indicate the existence of disease-specific subdomains. A hydrogen bond between residues 128 and 178 provides a structural basis for the observed highly specific influence of a polymorphism in position 129 in human PrP on the disease phenotype that segregates with the mutation Asp-178-Asn. Overall, the NMR structure implies that only part of the disease-related amino acid replacements lead to reduced stability of the cellular form of PrP, indicating that subtle structural differences in the mutant proteins may affect intermolecular signaling in a variety of different ways.     

Acute villous atrophy due to intolerance to soy bean protein

In infancy, intolerance to soybean protein may be associated with cow's milk protein intolerance. In the reported case, the intolerance to soybean had clinical expression. In addition, this intolerance was expressed on the histological level with severe villous atrophy which subsided 18 days after the suppression of soybean from the diet. These facts invite to administer soybean proteins with caution in patients with cow's milk intolerance.     

Hemodialysis catheter placement and recirculation in treatment of hyperammonemia

A 2-year-old girl with carbamoyl phosphate synthetase deficiency underwent emergency hemodialysis (HD) for treatment of acute life-threatening hyperammonemia. HD was performed via catheters placed in each femoral vein serving as vascular access. The tip of one of the catheters (aspirating line) was in the left external iliac vein and the tip of the other catheter (the return line) was in the inferior vena cava (IVC). High blood flow rates were used in order to rapidly lower the blood ammonia (NH3) levels. However, unanticipated marked recirculation in the IVC, between the dialysis aspirating and return catheters, was encountered, preventing significant reduction in blood NH3. The recognition of this problem, suggested solutions, and prevention are described.     

Persistent hyperammonemia in two related Morgan weanlings

Carcinoid tumors have been described in almost every organ and may affect virtually every body system. Cardiac involvement manifesting as right-sided valvular disease is characteristic of the carcinoid syndrome; however, direct myocardial involvement is unusual. We present a case of an invasive carcinoid tumor whose primary manifestation was myocardial invasion.     

Partial portal vein and mesenteric vein thrombosis in familial protein S deficiency

Protein S, a vitamin-K dependent glycoprotein is a cofactor of protein-C system, which acts as an inhibitor of the plasmatic coagulation. Protein-S congenital deficiency results in recurrent venous thromboses, atypical locations in portal and mesenteric veins are possible. In our patient the partial thrombosis of the portal vein was diagnosed by computed tomography and angiography. Small bowel ischaemia due to mesenteric vein thrombosis required segmental resection. Post-operatively the patient was heparinized and later phenprocoumon was applied to a long-term therapy.     

Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance

We describe 4 cases of lysinuric protein intolerance, which all fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. Mature histiocytes and neutrophil precursors participated in hemophagocytosis in the bone marrow. Moreover, serum levels of ferritin and lactate dehydrogenase were elevated, hypercytokinemia was present, and soluble interleukin-2 receptor levels were increased up to 18.6-fold. The diagnosis of lysinuric protein intolerance should therefore be considered in any patient presenting with hemophagocytic lymphohistiocytosis.     

Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset

Hyperammonemia and encephalopathy developed in an 11-year-old girl with chronic interstitial lung disease and cholesterol casts in her lung biopsy specimen. She had decreased plasma levels of ornithine, lysine, and arginine and excessive urinary excretion of lysine and arginine, consistent with the diagnosis of lysinuric protein intolerance. Analysis of plasma and urinary amino acids should be considered in the diagnostic evaluation of patients with interstitial lung disease of uncertain origin.     

Fatal hyperammonemia in a patient with systemic lupus erythematosus

We treated a 31-year-old woman with systemic lupus erythematosus, renal failure with nephrotic syndrome, and a long-standing seizure disorder, who developed severe hyperammonemia with a fatal outcome. Blood chemistry examination did not indicate liver disease, and amino acid concentrations did not suggest a defect in the urea cycle. Discontinuation of anticonvulsant treatment with valproic acid (VPA) failed to bring about improvement. We speculated that hyperammonemia in this case was induced by VPA, and the existence of other underlying factors, including the administration of aspirin and cimetidine, hypoalbuminemia, and renal failure might elevate the concentration of the serum free fraction of VPA.     

Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy

BACKGROUND: Mutations in the gene for cardiac myosin-binding protein C account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy. The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown. METHODS: DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574 family members at risk of inheriting these defects. The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed. RESULTS: Twelve novel mutations were identified in probands from 16 families. Four were missense mutations; eight defects (insertions, deletions, and splice mutations) were predicted to truncate cardiac myosin-binding protein C. The clinical expression of either missense or truncation mutations was similar to that observed for other genetic causes of hypertrophic cardiomyopathy, but the age at onset of the disease differed markedly. Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years. Survival was generally better than that observed among patients with hypertrophic cardiomyopathy caused by other mutations in the genes for sarcomere proteins. Most deaths due to cardiac causes in these families occurred suddenly. CONCLUSIONS: The clinical expression of mutations in the gene for cardiac myosin-binding protein C is often delayed until middle age or old age. Delayed expression of cardiac hypertrophy and a favorable clinical course may hinder recognition of the heritable nature of mutations in the cardiac myosin-binding protein C gene. Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy.     

Auxological evaluation of children with cow's milk protein intolerance treated an elimination diet

A somatic development assesment, including the nutritive condition at the moment of diagnosis and after at least a year's dietary treatment was carried out in a group of 55 children with primary cow's milk protein intolerance. The influence of the applied elimination diet and/or anti-allergic supporting treatment on the clinical picture was evaluated as well as calcium--phosphorus--magnesium balance parameters.     

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.     

Nursing caries and lactose intolerance

Caries is associated with fermentable carbohydrates in the diet. Dietary content can be related to personal and cultural preferences, availability of food, or physiologic tolerances. Twenty-seven percent of black children ages 12 to 24 months, in the Baltimore area were reported with symptoms of lactose intolerance. The incidence of lactose intolerance increased to 33 percent by age six years. At the same time, clinical observations of this same population suggested a high prevalence of nursing caries. One purpose of this study was to determine whether parents of black children with nursing caries perceived in their children more severe symptoms of lactose intolerance, which they related to milk products, than did parents of caries-free black children. A second purpose was to determine whether there were differences in feeding habits and types of fluids given children with nursing caries compared with caries-free children. A questionnaire concerning symptoms consistent with lactose intolerance, feeding habits, and fluid-selection was administered to the following groups: parents of 30 black children, ages 18 to 54 months, who were caries-free and parents of 30 black children, ages 18 to 54 months, diagnosed with nursing caries. Chi-square analysis or t-test analysis were performed on results accepting p < 0.05 as significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic glutamine synthetase deficiency in fatal hyperammonemia after lung transplantation

OBJECTIVES: We aimed to determine whether stethoscopes and otoscopes used in community paediatric clinics harboured pathogenic micro-organisms, and, if so, which measures could prevent this. METHODS: Fifty-five stethoscopes belonging to paediatric physicians working in 12 community clinics were sampled for bacterial cultures by two methods: (i) direct impression of the diaphragm and bell section of each stethoscope for 5 seconds onto blood agar plates and a mannitol-salt-agar plate; (ii) swabbing the entire surface of the diaphragm of the stethoscope with a sterile cotton-tipped applicator. Forty-two otoscopes from the same physicians were sampled by rubbing the handles of the otoscopes with cotton-tipped swabs. The plates were incubated at 37 degrees C for 48 hours and examined for colony growth at 24 and 48 hours of incubation. Culture results were recorded as mean numbers of colony-forming units (CFUs). Eight additional stethoscope diaphragms were chosen at random at the participating clinics and cultured as described above. They were then wiped with alcohol swabs (isopropyl alcohol 70%), allowed to air dry for approximately 10 minutes and cultured a second time. RESULTS: All the stethoscopes and 90% of the otoscope handles were colonized by microorganisms. Staphylococci were isolated from 85.4% of the stethoscopes and 83.3% of the otoscopes, with 54.5% and 45.2% respectively being S. Aureus. Methicillin-resistant S. aureus were found in four each of the stethoscopes (7.3%) and otoscopes (9.5%). Cleaning with alcohol reduced the colony count by an average of 96.3%. CONCLUSIONS: Fomites can harbour potentially pathogenic bacteria, and with the increasing trend for children with more complex medical problems to be managed in an ambulatory setting, often by physicians who also work in hospitals, there is a real risk of spreading potentially serious infections to such patients. Simple cleansing with alcohol effectively eliminates the bacterial contamination of the fomites, and should be encouraged.