Prenatal Diagnosis in High Risk Pregnancies for Zellweger Syndrome

Zellweger syndrome is a lethal disorder. At present, no effective therapies are known for the patients of Zellweger syndrome. Recently a typical case of Zellweger syndrome in Japan was observed. In spite of intensive care, the patient died at the age of 3 months. Following this, the parents requested prenatal diagnosis for their following two pregnancies.
We investigated levels of very long chain fatty acids (VLCFA), levels of bile acids in amniotic fluid and immunoblotting of peroxisomal β-oxidation enzymes in cultured amniocytes. We report that immunoblotting using cultured amniocytes is an effective method for prenatal diagnosis of Zellweger syndrome. Furthermore, if we use immunoblotting for prenatal diagnosis, we can discriminate pseudoZellweger syndrome from pseudoneonatal adrenoleucodystrophy.
Following prenatal diagnosis, two healthy babies were delivered. After birth, no abnormal levels of VLCFA in either serum or red blood cell membranes were confirmed. In this paper, we report that we can diagnose a healthy fetus in a high risk pregnancy for Zellweger syndrome.     

Standards for Growth and Growth Velocity in Turner's Syndrome

Turner-specific natural growth and growth velocity curves based on the retrospectively surveyed growth data of 704 Japanese patients in a mixed cross-sectional and longitudinal mode are reported. There was no significant difference in growth between the patients with karyotype 45,X and non-45,X. Twenty-three patients had a history of genital bleeding between the ages of 11 and 14 years (12 years ± 9 months). The mean height of the patients with genital bleeding did not differ significantly from that without bleeding from birth until 1 year 3 months of age but thereafter the former were always significantly taller than the latter. The former ceased growing after 18 years; on the other hand the latter were still growing after 18 years and then the final height of each group of patients became almost the same (139.6 ± 3.5 cm in the former and 139.1 ± 5.6 cm in the latter). A slight and gentle growth spurt was observed during the expected adolescent period in both groups, with and without genital bleeding. However, the mean height of peak (1.3 ± 0.95 cm/year) and the mean peak velocity (5.2 ± 1.1 cm/year) in the patients with genital bleeding were significantly higher than those (0.7 ± 0.36 and 3.8 ± 0.6 cm/year, respectively) in the patients without genital bleeding.     

A Case of Nephrotic Syndrome With Tetany

Abstract A 7-year-old girl with nephrotic syndrome had several attacks of tetany during the relapses. The attacks, acccompanied by hyperventilation, responded to re-breathing with a vinyl bag. However, other episodes of attacks which were not accompanied by hyperventilation, did not respond to re-breathing but responded to the intravenous administration of calcium gluconate. The serum concentrations of total calcium and ionized calcium were low and no calcium-binding protein was found in the serum from the patient, using chromatographic study. The serum concentration of 1, 25(OH)₂ vitamin D was within the normal range, but showed a tendency for the value to be lower in relapse than in remission. Urinary, Ca/Cr ratio in relation to serum calcium was high in this patient and a low threshold of calcium excretion in the kidney was demonstrated.
It is suggested that the impaired vitamin D metabolism and calcium loss in the urine might have contributed to tetany in this patient.
Administration of a calcium preparation and vitamin D may be necessary for a frequentrelapser on long-term glucocorticoid therapy.     

The 11q- Syndrome with Mosaic Partial Deletion of 11q

A female child with mosaic partial deletion of 1 lq is reported. At 1 month of age she was presented with congenital glaucoma, trigonocephaly and multiple minor anomalies. She exhibited growth retardation and the typical phenotype of llq- syndrome. G-banding analysis failed to show any abnormality, although subsequent high resolution banding revealed the abnormal karyotype mos 46,XX,del(11)(q23.3 q24.2)/46,XX,del(11)(q23.3 q25). This case is a second case of mosaic llq- syndrome and her karyotype suggests that the region of 11q23.3–11q24.2 is critical in 11q- syndrome. Congenital glaucoma has never been reported as a complication of llq- syndrome.     

Report of a Japanese Girl with Marfan Syndrome Associated with Insulin-Dependent Diabetes Mellitus

A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she Received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.     

Myelodysplastic Syndrome with Partial Deletion of the Long Arm of Chromosome 5: First Report of a Case in a Child

A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 × 10³/l with 3% atypical lymphocytes, and platelet count 17.7 × 10⁴/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases.
These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-.     

Hormonal and Genetical Assessment of a Japanese Girl with Weaver Syndrome

We report a case of Japanese girl with a rare disorder of Weaver syndrome, which was characterized by overgrowth with advanced and disharmonic bone age, craniofacial abnormalities, developmental delay, metaphyseal flaring of the long bones and camptodactyly. The patient was delivered at 38 weeks of gestation with a length of 54.2 cm (+ 2.6 SD), a weight of 3805 g (+ 2.5 SD) and an occipitofrontal circumference (OFC) of 35.0 cm (+ 1.1 SD). She manifested hypertonia and flexion contractures in the first few years. She also had submucosal soft cleft palate and difficulty in swallowing and breathing in early infancy. When she was 5 years and 7 months old, her height and weight were 133.3 cm (+ 5.5 SD) and 32.0 kg (+ 5.1 SD), respectively. We could not detect any endocrinological abnormalities for the cause of overgrowth. According to clinical features, Weaver syndrome was suspected and genetical analysis was performed. Fluorescence in situ hybridization (FISH) and direct sequencing analysis showed neither deletion nor point mutation of the nuclear receptor SET-domain-containing protein 1 (NSD1) gene on 5q35, which is responsible for Sotos syndrome. Therefore, we made a diagnosis of Weaver syndrome for this patient and discussed the differential diagnosis in terms of overgrowth syndrome.     

Continuous naloxone infusion for opiate poisoning in infancy

I report the successful treatment of severe infantile opiate poisoning with continuous naloxone infusions. Two infants, one aged 12 months and the other 3 days, were intoxicated with 100 mg normethadone and 5 mg morphine, respectively. They were given constant infusions of 0.04 and 0.16 mg/kg/hr for 2 1/2 and 5 days, respectively. Continuous naloxone infusion should be considered in the management of severe opiate poisoning.     

Ontogeny modifies manifestations of cystinuria genes: implications for counseling

Among 339,868 newborn infants screened at 3 weeks of age (91% compliance rate), 730 had elevated rates of excretion of cystine and the dibasic amino acids lysine, ornithine, and arginine; 191 infants had persistent "infantile cystinuria" on follow-up screening (100% compliance). Apparent incidence of the phenotype was 562 per million infants; this rate is seven times higher than for classic cystinuria in the adult segment of the Quebec population. We studied longitudinally 26 probands 2 to 4 months of age. Initially, each excreted cystine and dibasic amino acids at much higher levels than did normal infants or either parent. From parental phenotypes (heterozygous or homozygous normal) and urine amino acid excretion values at 6 months of age in probands, the infants were classified as either heterozygous for the various classic cystinuria genotypes--type I ("silent"), eight infants; type II (high excretor), three; type III (moderate excretor), nine--or homozygous (and genetic compound), six. Urine amino acid excretion diminished steadily with age, to reach the variant parental value in heterozygous infants but not in homozygotes. Cystinuria heterozygotes, with the possible exception of some type I individuals, could not be distinguished reliably from homozygotes in early infancy, although homozygotes had significantly higher excretion values as a group. We deduce that renal ontogeny amplifies phenotypic expression of cystinuria alleles, thus influencing correct classification of genotype (heterozygote vs homozygote, and type of allele). These findings have implications for counseling and the need for follow-up of infantile cystinuria.     

Trauma to the bones of small infants from passive exercise: a factor in the etiology of child abuse

Four infants, three premature and one term, developed serious bony injury from parent- or caretaker-administered passive exercises. In the three infants born prematurely, the exercise program was prescribed by neonatal intensive care unit staff before discharge; in the fourth infant, the babysitter initiated the program. In each case the passive exercise was begun to diminish actual or presumed muscle tightness. When these infants were presented to the physician with a serious traumatic injury between the ages of 4 and 10 months, the presumptive diagnosis of child abuse was made after radiologic assessment revealed multiple bone injuries. The several traumatic injuries to bones resulting from the home-administered physical therapy were most impressive. Passive exercise in three of the four infants was a significant factor in the cause of their injuries. Caution must be used in prescribing this form of "therapy" in small infants.     

Evaluation of a serum IgA-class reticulin antibody test for the detection of childhood celiac disease

Serum IgA class reticulin antibody (RA) was found in 28 (97%) of 29 children with flat small bowel mucosa, and in low titer in four (2%) of 245 with normal or near normal mucosa on small intestinal biopsy. Thus the sensitivity of the IgA-RA fluorescent antibody test for screening of celiac disease was 97% and the specificity 98%. IgA-RA was superior to IgG-RA for the detection of celiac disease. During follow-up of patients receiving a gluten-free diet, the IgA-RA rapidly decreased and in most cases disappeared within a year, suggesting that the test may be useful for clinical follow-up of celiac disease as well.     

Propranolol therapy for portal hypertension in children

Administration of propranolol to 13 children with portal hypertension reduced splenic pulp pressure by greater than 50 mm H2O (P less than 0.01) in approximately 2 weeks, when the pulse rate became three fourths the initial rate. The influence was found to be greater in compensated than in decompensated portal hypertension. This observation might be interpreted to mean that the effect of propranolol in the reduction of portal venous pressure results not only from decreased intestinal blood flow secondary to decreased cardiac output but also to the stimulation of sympathetic nervous system alpha-adrenoreceptors of the portal tract. Although arterial blood pressure changes were not significant, peripheral venous pressure was reduced significantly (P less than 0.01). We conclude that propranolol has considerable usefulness in treating portal hypertension in children.     

Thermal support for the very-low-birth-weight infant: role of supplemental conductive heat

Heated water pads were placed underneath very-low-birth-weight preterm infants receiving care under overhead radiant warmers with plastic heat shields to evaluate the effects on their thermal environments. The electrical input (watts) to the overhead warmer was monitored and temperatures at various locations in the environment and on the infants were recorded. The electrical input to the radiant warmers decreased significantly (P = 0.0015) with the introduction of the heated water pads. Several of the temperatures recorded during the study also showed significant changes, including increased abdominal skin temperatures in these prone infants (P = 0.007) and decreased back-to-abdomen skin temperature gradients (P = 0.007). Less marked changes included higher mattress or pad temperatures (P = 0.019), lower ambient air temperatures within the plastic heat shields (P = 0.022), and increased infant foot temperatures (P = 0.036). We believe that conduction has a significant influence on the thermal environment of the VLBW infant cared for under an overhead radiant warmer and that the use of a heated water pad can markedly alter heat transfer. The impact of conduction appears to have been previously underestimated.