EXCESSIVE HEPATIC GLYCOGEN STORAGE IN GLUCOSEPHOSPHATE ISOMERASE DEFICIENCY

Abstract. Excessive amounts of glycogen were found in liver and erythrocytes of a patient suffering from generalized glucosephosphate isomerase deficiency. A low carbohydrate diet, frequent meals and avoidance of peak carbohydrate challenges resulted in a significant decrease of liver volume without affecting the haematological condition. The possible mechanism of these findings are discussed.     

ANTIBODY DEFICIENCY SYNDROME AND AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A BOY WITH ISOLATED IgM DEFICIENCY DYSIMMUNOGLOBULINAEMIA TYPE 5

This paper describes a boy who suffered from severe recurrent infections from the first year of life. A brother with similar symptoms died from meningococcal meningitis. Virtually no IgM was demonstrable in the patient's serum, and it is suggested that the antibody deficiency syndrome in this case was based on a familial congenital disturbance in IgM synthesis. A study of antibody formation disclosed that disturbances existed in the formation of antibodies assumed to be contained in IgM; other antibodies were produced in adequate amounts. The significance of these findings is discussed in some detail. The boy subsequently developed autoimmune haemolytic anaemia. The question whether this was caused by the IgM deficiency or whether the immunological imbalance was based on a general disorder must remain unanswered.     

GLUCOSE-6-PHOSPHATE DEHYDROGENASE AND RED CELL PYRUVATE KINASE DEFICIENCY IN NEONATAL JAUNDICE CASES IN EGYPT

Glucose-6-phosphate dehydrogenase (G6PD) deficiency can lead to acute hemolytic anemia, chronic nonspherocytic hemolytic anemia, and neonatal jaundice. Neonatal red cell pyruvate kinase (PK) deficiency may cause clinical patterns, ranging from extremely severe hemolytic anemia to moderate jaundice. The authors aimed at studying the prevalence of G6PD and PK deficiency among Egyptian neonates with pathological indirect hyperbilirubinemia in Cairo. This case-series study included 69 newborns with unconjugated hyperbilirubinemia. All were subjected to clinical history, laboratory investigations, e.g., complete blood counts, reticulocytic counts, direct and indirect serum bilirubin levels, Coombs tests, qualitative assay of G6PD activity by methemoglobin reduction test, and measurement of erythrocytic PK levels. The study detected 10 neonates with G6PD deficiency, which means that the prevalence of G6PD deficiency among Egyptian neonates with hyperbilirubinemia is 14.4% (21.2% of males). G6PD deficiency was significantly higher in males than females (P = .01). The authors detected 2 cases with PK deficiency, making the prevalence of its deficiency 2.8%. These data demonstrate that G6PD deficiency is an important cause for neonatal jaundice in Egyptians. Neonatal screening for its deficiency is recommended. PK deficiency is not a common cause of neonatal jaundice. However, this needs further investigation on a larger scale.     

METACHROMATIC LEUKODYSTROPHY AND PSEUDOARYLSULFATASE A DEFICIENCY IN A DANISH FAMILY

ABSTRACT. A child with a diagnosis of lateinfantile metachromatic leukodystrophy (MLD), and a normal father with low arylsulfatase A (ASA) activity in leucocytes and cultured fibroblasts is described. The child had a pathologically increased amount of sulfatides in the urine, whereas no sulfatides could be found in the father's urine. Sulfatide-loading of the child's cultured fibroblasts showed an accumulation of sulfatides, whereas the fibroblasts from the father had a marginally decreased sulfatide turnover. It is thus possible to discriminate between these two forms of low ASA activity in this family, and to ensure a correct diagnosis should the amniotic fluid cells show a low ASA activity in future pregnancles.     

2,3-DIPHOSPHOGLYCERATE LEVELS IN CHILDREN WITH IRON DEFICIENCY ANEMIA AND ACUTE LEUKEMIA

Abstract. Red cell organic phosphates and especially 2,3-diphosphoglycerate (2,3-DPG), lowers the oxygen affinity of hemoglobin (Hb) and shifts the oxygen dissociation curve to the right. Because of the importance of 2,3-DPG (as regulator of the oxygen affinity of Hb), determinations were carried out on: 45 normal children, 7 children with iron deficiency anemia and 35 children with acute lymphoblastic leukemia. In normal children with Hb of 12.69±1.60 g/100 ml, 2,3-DPG was 14.90±0.68 μmoles/g Hb. In children with iron deficiency anemia (Hb 7.94±1.20 g/100 ml), 2,3-DPG was 20.87±3.11 μmoles/g Hb. 2,3-DPG was normal (14.11±0.88 μmoles/g Hb), in 16 patients with acute lymphoblastic leukemia who had never relapsed, while in 19 patients with a history of one or more relapses, 2,3-DPG levels were increased (22.05 ±2.75 μmoles/g Hb). No good explanation may be offered for the high 2,3-DPG levels in these leukemic children.     

A novel G6PD mutation leading to chronic hemolytic anemia

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important cause of hemolytic anemia worldwide. Severely affected patients have chronic hemolysis with exacerbations following oxidative stress. Mutations causing severe chronic non-spherocytic hemolytic anemia (CNSHA) commonly cluster in Exon 10, a region important for protein dimerization. An African-American male presented at age 2 weeks with pallor and jaundice, and was found to have hemolytic anemia with G6PD deficiency. His severe clinical course was inconsistent with the expected G6PD A(-) variant. DNA sequencing revealed two common mutations (A(-)) and a third novel Exon 10 mutation. This inherited haplotype represents a novel triple G6PD coding mutation causing chronic hemolysis.     

PANCYTOPENIA DUE TO VITAMIN B12 DEFICIENCY IN A BREAST-FED INFANT

Nutritional B12 deficiency in childhood is an uncommon disorder. Most cases are due to maternal insufficiency, resulting from deficient stores and intake, and is generally seen in exclusively breast fed infants. This report describes a breast-fed infant with megaloblastic anemia secondary to maternal vitamin B12 deficiency. We describe this patient to remind readers that B12 deficiency may cause severe pancytopenia and regression of motor functions. These patients can present with unexpected signs and symptoms, such as developmental delay and regression as in our patient. It is also important to take the nutritional history of both the child and the mother of early prevention and treatment. With early awareness and appropriate measures potentially irreversible neurologic damage can be prevented in the infant.     

WARM AUTOIMMUNE HEMOLYTIC ANEMIA FOLLOWING RECURRENT MYCOPLASMA PNEUMONIA INFECTIONS IN A CHILD WITH DOWN SYNDROME

Mycoplasma pneumonia (MP) is mainly associated with cold agglutinin syndrome, whereas both cold IgM and warm IgG autoantibodies have been identified in only two cases in the literature. The authors present an 8-year-old boy with Down syndrome, who suffered from recurrent episodes of MP infection, followed by episodes of hemolytic anemia with normal titer of cold agglutinins. The first 6 episodes were sequenced by nonimmune hemolytic anemia, whereas the latter 7 episodes were followed by episodes of warm autoimmune hemolytic anemia. This is believed to be the first described case of hemolytic anemia with warm IgG autoantibodies, following MP infection.     

5-OXOPROLINURIA DUE TO HEREDITARY 5-OXOPROLINASE DEFICIENCY IN TWO BROTHERS–A NEW INBORN ERROR OF THE γ-GLUTAMYL CYCLE

ABSTRACT. Larsson, A., Mattsson, B., Wauters, E. A. K., van Gool, J. D., Duran, M. and adman, S. K. (Department of Paediatrics, Karolinska Institute, St. Goran's Children's Hospital, Stockholm, Sweden, and University Children's Hospital, "Het Wilhelmina Kinderziekenhuis", Utrecht, The Netherlands). 5-Oxoprolinuria due to 5-oxoproIinase deficiency in two brothers–a new inborn error of the γ-glutamyl cycle. Acta Paediatr Scand, 70:301, 1981.–Two brothers, aged 16 and 11 years, had recurrent episodes of vomiting, diarrhoea and abdominal pain, starting in infancy. In spite of extensive investigations no cause of their enterocolitis could be established. After several years symptomatic treatment was discontinued without any recurrence of symptoms. Their father and several paternal relatives have had kidney stones. Both boys developed urolithiasis and an oxalate-containing stone was removed from the elder brother's kidney. He had no hypercalciuria. His glomerular and tubular function tests were normal. Gas chromatography of urine from both brothers revealed massive excretion of L-5-oxoproline (pyroglutamic acid). Glutathione levels in erythrocytes of both patients were normal. The activities of enzymes of the γ-glutamyl cycle were analysed in erythrocytes, leukocytes and cultured skin fibroblasts. The level of glutathione synthetase was normal, as was the affinity of this enzyme for its substrate γ-glutamyl-cysteine. Feedback inhibition of γ-glutamyl-cysteine synthetase by glutathione was also normal. Both patients had a specific deficiency of 5-oxoprolinase, the activity of which was 2-A % of that of control subjects. Their parents had intermediate 5-oxoprolinase activities in fibroblasts, indicating a recessive mode of inheritance. Thus, 5-oxoprolinuria in these two patients was due to a lack of S-oxoprolinase, i.e., a new inborn error in the γ-glutamyl cycle.     

THE CUTIS VERTICIS GYRATA AND MENTAL RETARDATION SYNDROME IN A 4-YEAR-OLD BOY

A 4-year-old profoundly mentally retarded boy with cutis verticis gyrata is described. He had four folds on the left parietal region, small asymmetric head, micrognathia, short neck, marmorated skin, thoracic scoliosis, spastic tetraplegia and epilepsy. Encephalography revealed marked asymmetric macroventriculy with hypoplastic brain stem and cerebellum. Thorn's test and corticotrophin stimulation test gave normal responses. The boy is the youngest patient with the cutis verticis gyrata and mental retardation syndrome described in the literature. The numerous malformations of the patient strongly support the theory of prenatal origin of the cutis verticis gyrata and mental retardation syndrome.     

A TWO-CENTURY PERSPECTIVE OF SOME MAJOR NUTRITIONAL DEFICIENCY DISEASES IN CHILDHOOD

ABSTRACT: Vahlquist, B. (Department of Paediatrics, University Hospital, Uppsala, Sweden). A two-century perspective of some major nutritional deficiency diseases in childhood. Acta Paediatr Scand, 64:161, 1975.–In this review, dealing with historical aspects and the present day situation in developing countries, three major nutritional deficiencies among children are discussed, namely rickets, iron deficiency anaemia and protein energy malnutrition (PEM).     

EFFECT OF OROTIC ACID UPON SERUM BILIRUBIN IN NEWBORN INFANTS WITH ERYTHROCYTE G-6-PD DEFICIENCY

Fifty mature male newborns with erythrocyte G-6-PD deficiency were used for a study con cerning the effectiveness of orotic acid in preventing severe hyperbilirubinemia. Twentyfive randomly selected neonates were given orotic acid (100 mg/kg/day) orally in two daily doses from their 1st to their 5th day of life. Twenty-five newborns were not treated According to these results orotic acid does not seem to be effective in preventing severe hyperbilirubinemia, which frequently occurs in newborn babies' with erythrocyte G-6-PD deficiency. and served as controls. Six exchange transfusions were performed in the test group and six in the controls.     

DIETARY TREATMENT IN HYPERPROLINAEMIA TYPE II

Abstract. Similä, S. (Department of Paediatrics, University of Oulu, Oulu, Finland). Dietary treatment in hyperprolinaemia Type II. Acta Paediat Scand 63:249, 1974.–Hyperprolinaemia type II was diagnosed in a half-year-old boy (prohand) with convulsions and an encephalitis-like period, and his symptomless brother aged 7 years. The plasma levels of proline were greatly elevated, 39.8 and 38.4 mg/100 ml, respectively. The urinary excretion of free proline and δ'-pyrroline-5-carhoxylic acid (SPC) was increased. Reduction of the dietary proline of the prohand after the first encephalitis-like period at the age of 7 months resulted in a slight decline of the plasma proline level and of the urinary excretion of proline and SPC. After a 14-month dietary period convulsions began to recur, and an encephalitis-like period followed. Thereafter, with a more restricted proline (90 mg/kg per day) intake, the decline of the plasma level of proline was clear. During a 3 years' period of dietary treatment the patient's growth and mental development were satisfactory, hut the electroencephalogram abnormalities remained. Restriction of dietary proline in the hyperprolinaemic brother resulted in a prompt fall of the plasma level of proline. The restriction of proline, however, did not normalize the elevated plasma level of proline, and the urinary excretion of 5PC did not cease completely. These results suggest that endogenous synthesis is not an important source of circulating proline. Restriction of dietary proline in hyperprolinaemia type II may be necessary during infancy at least if the plasma level of proline is greatly elevated as in our prohand.     

JUVENILE CIRRHOSIS AND MEMBRANOUS GLOMERULONEPHRITIS IN A CHILD WITH ALPHA1ANTITRYPSIN DEFICIENCY PiSZ

ABSTRACT. An infant with alpha₁-antitrypsin (α₁-AT) deficiency PiSZ presented with liver cirrhosis and showed clinical and laboratory evidence of renal disease when hepatic decompensation developed, shortly before death at 12 months of age. Low serum levels of α₁-AT were only demonstrated late in the disease. SZ phenotype was proved by starch gel electrophoresis. Post-mortem pathological studies revealed sevre hepatic cirrhosis with intracytoplasmic inclusion of α₁-AT and membranous glomerulonephritis with deposits of complement and immunoglobulins but without the presence of α₁-AT. The present case suggests the importance of studying Pi phenotypes and serum levels of α₁-AT in all cases of idiopathic cirrhosis or renal disease in infancy.     

PRIMARY HYPOTHYROIDISM, GROWTH HORMONE DEFICIENCY AND CONGENITAL MALFORMATIONS IN A CHILD WITH THE KARYOTYPE 46, XY, del(l)(q25q32)

Abstract. Primary thyroidal hypothyroidism, growth hormone deficiency, congenital malformations and mental retardation occurred in a child with an interstitial deletion of one of the No. 1 chromosomes. Two bands were missing, so that the karyotype could be written: del(l)(pter→q25::q32→qter). The possible relationship between the clinical features and chromosomal deletion are discussed.     

SEVERE MENTAL RETARDATION IN A SWEDISH COUNTY I. Epidemiology, Gestational Age, Birth Weight and Associated CNS Handicaps in Children Born 1959–70

Abstract. In an unselected series of children born in 1959–70 with severe mental retardation (MR)-defined as IQ<50–in a Swedish county, the incidence, prevalence, gestational length, birth weight and associated CNS handicaps were analysed. The cumulative incidence at 1–16 years of age was calculated at 3.3‰ and the prevalence at 11–16 years at 2.8‰. These figures were lower than in most other previous studies. In the great majority of cases the pathogenesis was of prenatal origin. The mean gestational lengths and birth weights were decreased compared with those of an average Swedish population. Severe MR affected large and small for date babies more often than could be expected. On the other hand, babies, with a low birth weight, appropriate for gestational age, and with an uncomplicated history, were found not to run a special risk of severe MR. Among the 122 children, 42% had one or more associated CNS handicaps—epilepsy (30%) and cerebral palsy (18%) being the most common.     

THE EFFECT OF VARIOUS THERAPEUTIC TRIALS ON THE PORPHYRIN EXCRETION IN A CASE OF CONGENITAL ERYTHROPOIETIC PORPHYRIA

ABSTRACT: Eriksen, L. and Seip, M. (Institute of Physiology, University of Oslo, and Department of Pediatrics, University Hospital, Oslo, Norway). The effect of various therapeutic trials on the porphyrin excretion in a case of congenital erythropoietic porphyria. Acta Paediatr Scand 64:287, 1975.–A patient with a biochemically "new" type of congenital erythropoietic porphyria has been studied under various therapeutic trials. Splenectomy had no demonstrable effect on porphyrin excretion or clinical picture. Vitamin E caused a moderate fall in porphyrin excretion, however, there was no significant improvement in light tolerance and tendency to hemolysis. β-carotene reduced skin photosensitivity appreciably, while total porphyrin excretion remained unchanged and the tendency to develop hemolytic anemia showed only slight improvement. Red cell transfusion caused a rapid, dramatic fall in porphyrin excretion (in 4–5 days) and a transient increase in light tolerance, while the distribution of the different porphyrins excreted remained unchanged. These observations indicate that all or nearly all the abnormal porphyrins excreted are of erythropoietic origin, and that the overwhelming part of the porphyrins originate from an abnormal population of shortlived red cells. Findings on fluorescence microscopy of blood and bone marrow support this view. Meticulous protection against light of the shorter wavelengths caused a similar rise in hemoglobin level as produced by red cell transfusion, however, in this instance the total excretion of porphyrins did not fall. It is suggested that the inhibitory effect of transfusion on erythropoiesis (and thereby porphyrin excretion) might be due partly to a depression of erythropoietin formation, partly to the presence of an erythropoiesis inhibiting factor (chalone) in the transfused red cells.