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Background Congenital chloride diarrhea (CCD) is a rare inherited disorder of intestinal electrolyte transport that results in a large wastage of electrolytes and water. Advances in substitution therapy using sodium chloride (NaCl) and potassium chloride (KCl) have dramatically improved survival for patients with CCD. Slow-release KCl is widely prescribed as a potassium supplement; however, it has also occasionally been used in suicide attempts, as potassium poisoning can generate life-threatening hyperkalemia. Case summary A 26-year-old female presented to the emergency department (ED) with self-poisoning, having taken 30 tablets of slow-release KCl (total: 240 mmol potassium) following an auditory hallucination. The patient had been undergoing substitution therapy with NaCl and KCl for CCD and been followed up in the pediatric department. One month prior, she developed insomnia and anxiety and had consulted a psychiatrist. At the ED, although her general condition was good, she appeared agitated. Her serum potassium level was 7.0 mmol/L, indicating hyperkalemia, and electrocardiographic changes showed tenting of the T-waves. She responded to the administration of calcium gluconate, sodium bicarbonate, and insulin with glucose, and the serum potassium level improved. Finally, she was diagnosed with schizophrenia. Conclusion In CCD management, physicians should pay careful attention to patients' extraintestinal issues, including psychological disorders that may emerge in adulthood.

Interstitial microdeletions at chromosome 19p13.3 are frequently associated with a constellation of clinical features including macrocephaly, characteristic face, intellectual disability, and sleep apnea. Previous studies in 25 patients with 19p13.3 microdeletions have revealed loss of MAP2K2 in 24 patients and that of PIAS4 and ZBTB7A in 23 patients, suggesting that these three adjacent genes are candidate genes for the phenotypic development in 19p13.3 microdeletions. We identified a de novo likely pathogenic heterozygous missense variant of ZBTB7A (NM_015898.3:c.1152C>G, p.(Cys384Trp)) in a Japanese boy with macrocephaly, intellectual disability, and sleep apnea. This variant affects the conserved cysteine residue forming the coordinate bond with Zn2+ ion at the first zinc finger domain, and is predicted to exert a dominant-negative effect because of the generation of homo- and hetero-dimers with the wild-type and variant ZBTB7A proteins. The results argue for a critical relevance of ZBTB7A to the development of most, but probably not all, of the 19p13.3 microdeletion phenotype.

Pheochromocytoma during pregnancy is rare but potentially harmful to the mother and fetus. Fetal risks are mainly determined by the vasoconstrictive effects of maternal catecholamine on uteroplacental circulation, because the fetus is protected from the direct effects of high catecholamine levels at the placental interface. Uteroplacental insufficiency may lead to spontaneous abortion, fetal growth restriction, premature delivery, and fetal hypoxia, followed by fetal distress and/or birth asphyxia. Adrenalectomy is recommended during the second trimester. When a diagnosis is made during the late second or third trimester, appropriate medical treatment until term and planned delivery with concurrent or delayed adrenalectomy can result in good fetal outcomes. Moreover, when adrenalectomy is planned after delivery, there is concern regarding the potential of antihypertensive drugs to be transferred to breast milk. It is generally known that early detection and proper treatment of pheochromocytoma during pregnancy decrease maternal and fetal mortality. However, in recent case series, antenatal maternal pheochromocytoma diagnosis did not significantly decrease the risk of fetal and neonatal mortality and morbidity, contrary to the maternal death and complication rates. Although intrauterine ischemia and hypoxia due to uteroplacental insufficiency can affect the long-term outcomes of neonates, no systematic studies have been performed.

Radioactive iodine (131I) therapy is absolutely contraindicated in pregnancy, but reports of inadvertent exposure continue to appear in the literature. Radiation-induced effects on the embryo/fetus are highly dependent on the stage of pregnancy, the dose absorbed by the embryo/fetus, and the manifestations of the pathological condition that develops as a result of the irradiation. Prior to implantation, the major concern is death of the embryo when exposed to radiation greater than the 100 mGy threshold. At this very early stage of pregnancy, exposure to 131I is unlikely to cause major malformations or thyroid dysfunction in surviving embryos. Exposure during organogenesis of the thyroid (from 10 weeks of gestation onward) and that of other organs at radiation thresholds of 100-300 mGy may result in fetal thyroid ablation, malformations, growth restriction, and in later life, mental retardation (MR). In addition, any dose of radiation exposure may increase the risk of cancer many years after the in utero exposure. Fetal and neonatal hypothyroidism due to in utero 131I exposure may require lifelong thyroxine replacement therapy and result in severe MR if the condition is not recognized immediately. Therefore, thyroid function must be evaluated and replacement therapy should be started without delay even before birth. Physicians treating women of childbearing age with 131I need to be aware of the risks of in utero 131I exposure and take all measures to avoid inadvertent exposure during pregnancy. Nevertheless, in case of accidental exposure, the clinician should confirm the gestational age at exposure, evaluate the risks to the fetus by estimating the radiation dose delivered, and discuss the subsequent management plan with the pregnant woman. This review aimed to summarize the current knowledge regarding the risk of harm to the developing fetus after in utero 131I exposure, especially focusing on the effects on thyroid function. This study also evaluated the most significant new findings regarding the prevention and in utero and peripartum management of fetal exposure to 131I.

AIM To evaluate the association between small for gestational age (SGA) and the prevalence of congenital heart disease (CHD) and the association of the SGA status with the outcomes among infants with CHD. METHODS Echocardiography was performed within the first 5 days of life in 5664 consecutive infants. Infants were classified into four groups according to the presence or absence of SGA and CHD. All CHD infants were followed up until either spontaneous resolution of all cardiac lesions, invasive intervention or death. All newborns without CHD were followed for mortality until the final follow-up date. RESULTS A total of 303 infants were diagnosed with CHD, while 610 were diagnosed with SGA. Among the CHD infants, 56 were SGA, and 247 were not. A multivariable logistic regression analysis showed that the adjusted odds ratio of SGA (9.71, P

Gestational transient thyrotoxicosis (GTT) is associated with direct stimulation of the maternal thyroid gland by human chorionic gonadotropin (hCG). It is characterized by slightly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels in early pregnancy and mild or no symptoms. While GTT must be distinguished from Graves' disease (GD), which is associated with maternal and fetal complications, treated GD and new-onset GD in pregnancy are occasionally challenging to distinguish. Evaluating serum hCG levels and TSH receptor antibody (TRAb) titers can help, but the results are not irrefutable due to pregnancy-related immunosuppression. Moreover, GTT can follow unusual clinical courses in relation to some pregnancy complications. Excessive hCG production can cause severe GTT symptoms in patients with hyperemesis gravidarum, trophoblastic disease, or multiple pregnancies. Thyrotoxicosis can emerge beyond the second trimester in patients with gestational diabetes mellitus and mirror syndrome, because of delayed elevations in the hCG levels. Detailed knowledge about GTT is necessary for correct diagnoses and its appropriate management. This review focuses on the diagnosis of GTT, and, particularly, its differentiation from GD, and unusual clinical conditions associated with GTT that require comprehensive management.

Cardiac insufficiency is a major morbidity in neonatal hyperthyroidism. It is important to assess the hemodynamics in neonates born to mothers with Graves’ disease (GD). This study prospectively evaluated the hemodynamic changes in neonates born to mothers with GD. Overall, 80 newborns were enrolled. Thirty-six neonates were born to mothers with GD who were positive for thyroid-stimulating hormone (TSH) receptor antibody (TRAb), and 44 were born to mother negative for TRAb. The serum levels of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), the cardiac output, and cardiac index (CI) evaluated by echocardiography were compared between the two groups at several postnatal points (day of delivery and 5, 10, and 30 days of life). The TRAb-positive newborns had higher FT4 levels and CI on Day 5 (both p

Objective: We aimed to determine the presence of seasonal and meteorological associations of the activity of vitamin K-dependent coagulation factors to explain the seasonal variation in vitamin K deficiency-related bleeding.Methods: Seasonal and monthly changes in Normotest values in 1,759 healthy 1-month-old infants were retrospectively accessed, and the impact of meteorological parameters on Normotest values was analyzed.Results: Normotest values peaked in winter and were the lowest in summer, with statistically significant differences among the seasonal values (p

Background: Thyroid hormones (THs) play a critical role in normal maturation of the developing brain in the fetus and infant. Continuing advances in neonatal medicine have contributed to an increased survival of extremely premature infants with neonatal morbidities. In these infants, thyroid system immaturities, as well as morbidity-related thyroid dysfunction, contribute to transient hypothyroxinemia of prematurity (THOP), which is characterized by very low total and free thyroxine and normal or low thyroid-stimulating hormone (TSH) levels.Review: Undoubtedly, low levels of THs with elevated TSH are associated with poor neurodevelopmental outcome. However, continuing debate exists regarding whether THOP is harmful to the developing brain. Moreover, no clear effects of TH treatment on neurodevelopmental outcome in preterm infants with THOP have been demonstrated. THs could have unpredictable effects if given unnecessarily.Conclusion: The current recommendation is to treat THOP with TH only if THOP...

Background Delayed diagnosis of critical congenital heart disease (CCHD) carries a serious risk of mortality, morbidity, and handicap. As echocardiography is commonly used to diagnose congenital heart disease (CHD), echocardiographic investigations in newborns may be helpful in detecting CCHD earlier and with higher sensitivity than when using other screening methods. The present study aimed to evaluate the effectiveness of echocardiographic screening for CCHD in a tertiary care center. Methods A retrospective chart review was conducted among newborns delivered at Hamamatsu University Hospital between June 2009 and May 2016. The study included consecutive newborns who underwent early echocardiographic screening (within the first 5 days of life) performed by pediatric cardiologists, were born at ≥36 weeks of gestation, had a birthweight ≥2300 g, and were cared for in the well-baby nursery. Newborns admitted to the neonatal intensive care unit, as well as those with prenatal diagnosis of CHD and/or clinical symptoms or signs of CHD were excluded. Four CHD outcome categories were defined: critical, serious, clinically significant, and clinically non-significant. Results A total of 4082 live newborns were delivered during the study period. Of 3434 newborns who met the inclusion criteria and had complete echocardiography data, 104 (3.0%) were diagnosed as having CHD. Among these, none was initially diagnosed as having critical or serious CHD. Of the 95 newborns who continued follow-up with a cardiologist, 61 (64%) were determined to have non-significant CHDs that resolved within 6 months of life. Review of excluded newborns revealed nine cases of critical or serious CHD; among these newborns, six were diagnosed prenatally and three had some clinical signs of CHD prior to hospital discharge. Conclusions In our tertiary care center, echocardiography screening within the first 5 days of life did not help improve CCHD detection rate in newborns without prenatal diagnosis or clinical signs of CHD. Echocardiographic screening may be associated with increased rate of false-positives (defects resulting in clinically non-significant CHDs) in newborns without prenatal diagnosis or suspicion of CHD.

A pregnancy complicated with rheumatologic diseases can have various influences on the fetus and/or neonate. Maternal systemic lupus erythematosus (SLE) may cause preterm and/or small for gestational age (SGA) delivery and neonatal lupus (NL). Some neonates with NL have congenital heart block (CHB) with increased morbidity and mortality, even requiring pacemakers. Antiphospholipid syndrome may occur with SLE and affect fetal and/or neonatal outcomes. Pregnancy involving primary Sjogren's syndrome (pSS) tends to result in preterm delivery and low birthweight infants. Moreover, CHB is the most challenging complication for neonates delivered by women with pSS. Pregnant women with rheumatoid arthritis (RA) are at an increased risk for delivering a preterm or SGA neonate. In addition, RA drugs may have adverse effects on the fetus and breast-fed neonate. With dermatomyositis/polymyositis, pregnancies are at increased risk for spontaneous abortion, perinatal death, and preterm delivery. At present, overall neonatal survival rates are good for pregnancies involving systemic sclerosis, despite an increased frequency of premature and SGA neonates. In conclusion, maternal rheumatological diseases require careful monitoring to ensure the best possible management for fetal and neonatal outcomes.

We report herein a case of early vitamin K deficiency bleeding (VKDB) in a neonate associated with maternal Crohn's disease. A female neonate was born at 37 weeks' gestation and weighed 2778 g. She developed broad purpura on her back on day 1. Laboratory data showed anemia, prolonged coagulation time and elevated protein induced by vitamin K absence or antagonist-II. Early VKDB has not been reported in a neonate born from mother with active Crohn's disease. It is essential to give vitamin K selectively as soon as possible after birth to prevent early VKDB in neonates.

Background The morbidity and mortality rates due to cardiovascular events such as myocardial infarction are known to exhibit seasonal variations. Moreover, changes in the ambient temperature are reportedly associated with an increase in these events, which may potentially involve blood coagulation markers. Bleeding due to vitamin K deficiency in neonates, which is associated with high mortality and a high frequency of neurological sequelae, is more commonly observed during the summer season and in warm regions in Japan. To determine the presence of seasonal variation and the influence of ambient temperature on blood coagulation markers in healthy term neonates, we assessed the international normalized ratio (INR) values measured using CoaguChek XS. Methods We studied 488 consecutive healthy term neonates who were born at a perinatal center between July 2012 and June 2013. The INR values were measured using CoaguChek XS in 4-day-old neonates who received nursing care in the newborn nursery throughout the duration of hospitalization. The seasonal variations in the INR values and environmental effects on the INR were assessed. Results The mean monthly INR values peaked in July (1.13 ± 0.08), whereas the lowest values were observed in January (1.05 ± 0.08). Higher levels of INR were observed during the summer season (June to August) than during the winter season (December to February). Simple linear regression analysis indicated the presence of weakly positive but significant correlations between INR and outdoor temperature (r = 0.25, p

Hemolytic anemia with abundant Heinz bodies developed in an extremely low birth weight infant. The infant was born at 25 weeks' gestation with a birth weight of 741 g. The disord er manifested at 28 days of age after the acute period. Results of a routine weekly blood examination showed an unexpected sudden fall in the hemoglobin level and an increased total bilir ubin level. Peripheral blood smear revealed that a high percentage of erythrocytes contained Heinz bodies. With repeated blood transfusions and aggressive phototherapy this condition resolved within a week. The patient had not been exposed to known toxins with oxidizing agents. Glucose-6-phosphate dehydrogenase levels were normal, and an unstable hemoglobin was not present. Although the cause and underlying mechanisms of this phenomenon are unknown, the immature antioxidant function of the erythrocyte membrane against oxygen radicals in an extremely premature infant might be a factor in the etiology.

We investigated time-related predictors of death or neurological sequelae in extremely preterm infants (EPI) born at 22 to 24 weeks' gestation by categorizing clinical patterns according to their survival time and morbidity. Data on 113 infants born at 22 to 24 weeks' gestation from January 1991 through April 2006 were analyzed by a case-control approach. Cesarean section, Apgar scoreor= 3 at 5 minutes, and pulmonary hypoplasia were significantly associated with death at24 hours of life. Among infants who survivedor= 24 hours, pulmonary hemorrhage and intraventricular hemorrhage (IVH) were significantly associated with death by day 6. Among those survivingor= 7 days, sepsis and severe IVH were significantly associated with death. Assessment of survivors at a minimum follow-up period of 2 years revealed that protracted mechanical ventilation was significantly associated with a poor neurological outcome. There are various characteristic key events in relation to the outcome at different ages of life in EPI born at 22 to 24 weeks' gestation. Clinicians and parents should discuss management options for the infant on the basis of these findings.

Congenital chloride diarrhea (CCD) is an inherited disorder of intestinal electrolyte transport that results in a large wastage of electrolytes and water. The patient, who is now 24 years old, was diagnosed at the age of 16 months with CCD based on hypochloremic alkalosis, hyponatremia, and hypokalemia with increased plasma renin and aldosterone levels, and high fecal Cl(-). Serum Na(+) and plasma aldosterone levels were normalized by replacement therapy with NaCl [8 mmol/(kg day)] and KCl [3 mmol/(kg day)]. On follow-up, watery diarrhea persisted, and she was frequently noted to have hypokalemia despite normal serum Na(+) and Cl(-) and plasma aldosterone levels with only reduced dosages of KCl [1-1.5 mmol/(kg day)] substitution due to only sporadic ambulatory care and unsatisfactory compliance with medication, and a normal diet. However, she had acceptable growth, normal renal function, and had an uneventful pregnancy and delivery of a healthy child. In adolescence and adulthood, hypokalemia may be the main problem requiring treatment, and substitution therapy with adequate doses of KCl alone may be sufficient, although a combination of NaCl and KCl is generally recommended even after childhood.

A male infant (gestational age, 26 weeks and 1 day; birthweight, 752 g) was treated for respiratory distress syndrome and thereafter required mechanical ventilation due to chronic pulmonary insufficiency. On the 34th day after birth, urine volume suddenly decreased and hypotension, oliguria, and generalized edema developed. Laboratory studies revealed rapid progression of severe hyponatremia and hyperkalemia. Although hypovolemic shock was suspected, the patient did not respond to conventional treatment of volume expansion and inotropic support. Only treatment with glucocorticoids was effective. Two weeks later, cranial ultrasonography revealed multiple, right-sided, cystic lesions that were subsequently diagnosed as cerebral infarction by magnetic resonance imaging. Several cases of extremely low birthweight infants with circulatory collapse after the acute period have been described recently, but the cause has been unclear. There has been no previous report of a case accompanied by cerebral infarction.

we examined the dynamics of bacterial contamination on the hands of nurses who were performing basic neonatal care and the efficacy of hand hygiene. The bacterial count on nurses, hands significantly increased after all care activities, and hand hygiene significantly reduced bacterial contamination. In conclusion, basic neonatal care, even if it is considered to be "clean" care, caused a significant increase in bacterial contamination of nurses' hands.

We investigated the postnatal pattern of changes in adrenal size in very low-birth-weight (VLBW) infants and its relation to late-onset glucocorticoid-responsive circulatory collapse (LGCC) that may be associated with adrenal insufficiency. In 36 VLBW infants born at

For patients with cytochrome P450 oxidoreductase deficiency (PORD), steroid replacement is recommended at times of stress. However, it is unknown how hormones respond to actual physical stress in these patients. We report a female infant with PORD accompanied by the Antley-Bixler syndrome phenotype. Her urinary steroid profile revealed defective CYP17A1 and CYP21A2 activities, and an adrenocorticotropin (ACTH) stimulation test showed potential adrenal insufficiency. Hormonal responses to actual physical stress were as follows: Vigorous crying during blood sampling rarely affected the serum cortisol level. Acute viral gastroenteritis led to marked increases in blood ACTH and 17alpha-hydroxyprogesterone levels in proportion to the severity of the illness. The serum cortisol level also responded to this stress, but the response might have been blunted. Regarding peri-operative steroid replacement, intravenous hydrocortisone administration even at a dose of 6 mg/kg, which is lower than that recommended for congenital adrenal hyperplasia in Japan, proved to be excessive.

©2008, World J Pediatr. All rights reserved. A female, born after normal pregnancy and labor, was referred for consultation for a 1-cm long fi brous appendage in the midline of her lumbosacral region one day after birth (Fig. 1). Although she was neurologically intact, computed tomography at 3 months revealed L4-L5 spina bifi da (Fig. 2A), and magnetic resonance imaging (MRI) showed a low conus medullaris level (L3), and a tethered dorsal spinal cord that seemed to connect with the site of the skin lesion (Fig. 2B). Spina bifi da occulta with tethered spinal cord due to a dermal sinus tract was diagnosed and the patient was treated surgically. At operation, the sinus tract extending from the skin to the spinal cord was observed, but the thickening of the fi lum terminale was not evident. Occult spinal dysraphism with tethered spinal cord, if not recognized, may result in permanent neurologic defi cits. Moreover, the neurological disturbances can be diffi cult to demonstrate in a young baby and clinical evaluation of bladder function is equally diffi cult at this age. To prevent serious sequelae, early screening of high-risk infants with cutaneous markers that present in 50%-90% of patients, radiologic diagnosis using X-rays, either MRI or sonography, and urodynamic testing, and the appropriate timing of surgical untethering should be performed. However, dorsal cutaneous lesions may be ignored unless they are common lesions such as midline hemangiomas, hairy patches, dimples or sinuses, or pigmented macules. In order to screen effectively, the physician must have a high degree of suspicion for such a rare skin abnormality as this case. References 1 Guggisberg D, Hadj-Rabia S, Viney C, Bodemer C, Brunelle F, Zerah M, et al. Skin markers of occult spinal dysraphism in children: a review of 54 cases. Arch Dermatol 2004;140:1109-1115. 2 Cornette L, Verpoorten C, Lagae L, Van Calenbergh F, Plets C, Vereecken R, et al. Tethered cord syndrome in occult spinal dysraphism: timing and outcome of surgical release. Neurology 1998;50:1761-1765. 3 Yamada S, Won DJ, Siddiqi J, Yamada SM. Tethered cord syndrome: overview of diagnosis and treatment. Neurol Res 2004;26:719-721. Received March 31, 2008 Accepted after revision May 8, 2008 A rare cutaneous sign of occult spinal dysraphism with tethered spinal cord

Although improvements in antimicrobial therapy during the last few decades have decreased mortality in childhood bacterial meningitis, some patients are left with neurologic sequelae. Cerebrovascular complications are often associated with unfavorable clinical outcome of the disease. We report a 36-day-old infant with severe, widespread cerebrovascular complications due to group B streptococcal meningitis. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) contributed to a non-invasive demonstration of meningeal inflammatory changes and vascular lesions with the meningitis in this patient.

The objective of this study was to clarify the relationship between the blood potassium and calcium levels, and the efficacy of prophylactic calcium (Ca) administration early in life for nonoliguric hyperkalemia in extremely low birthweight (ELBW) infants. This was a retrospective study including 55 ELBW infants with gestational age less than 26 weeks (mean, 24.4 weeks; mean body weight, 681 g). The plasma potassium concentration and whole blood ionized calcium (iCa) concentration were measured every 2 to 3 hours. Laboratory data obtained up to 24 hours after birth were collected. The infants were divided into two groups based on whether or not Ca gluconate was administered prophylactically starting at admission (prophylactic and nonprophylactic group). There was a negative correlation between the plasma potassium and iCa levels at 12 and 24 hours, and the maximum plasma potassium level was higher in the hypocalcemia group (minimum iCa level, < 0.9 mmol/L) than in the normocalcemia group. The iCa level was significantly higher and the plasma potassium level was significantly lower in the prophylactic group than in the nonprophylactic group at 12 and 24 hours. The increment in the plasma potassium level at 24 hours compared with that at admission was significantly lower in the prophylactic than in the nonprophylactic group. Nonoliguric hyperkalemia may be attenuated by maintaining the iCa level within normal limits by prophylactic Ca administration early in life. Prospective studies are needed to confirm this.

Background Neonates routinely receive vitamin K to prevent vitamin K deficiency bleeding, which is associated with a high mortality rate and a high frequency of neurological sequelae. A coagulation screening test might be necessary to detect prophylactic failure or incomplete prophylaxis. However, venous access and the volume of blood required for such testing can be problematic. CoaguChek XS is a portable device designed to monitor prothrombin time while only drawing a small volume of blood. Although the device is used in adults and children, studies have not been performed to evaluate its clinical utility in neonates, and the reference value is unknown in this population. The objectives of the present study were to determine the reference intervals (RIs) for international normalized ratio (INR) using the CoaguChek XS by capillary puncture in healthy term neonates, to evaluate factors that correlate with INR, and to evaluate the device by assessing its ease of use in clinical practice. Methods This study included 488 healthy term neonates born at a perinatal center between July 2012 and June 2013. The INRs determined by CoaguChek XS were measured in 4-day-old neonates. Results The enrolled neonates were orally administered vitamin K 6-12 h after birth. A RI for INRs in 4-day-old neonates was established using the CoaguChek XS with a median value of 1.10 and a range of 0.90–1.30. A significant difference in the INR was noted between male (median value, 1.10; RI, 0.90–1.30) and female (median value, 1.10; RI, 0.90–1.24) neonates (p = 0.049). The INR was found to correlate with gestational age, birth weight, and hematocrit value. Conclusions The CoaguChek XS device is safe, fast, and convenient for performing INR assays in neonates. Our study is the first to establish a RI for INRs that were measured using the CoaguChek XS in healthy term neonates.

A 12 year old boy was admitted to our hospital because of short stature. From the age of 7, his growth velocity decreased and he manifested intolerance to low temperatures, hoarseness, dry skin, and slowness of thought and physical movement. On admission, his height was 129.8 cm (-3 s.d.) and his body weight was 43.2 kg (-0.5 s.d.). His clinical features also included relaxation phase of tendon reflexes, periorbital puffiness and cold skin but no struma. His bone age was 9 years. His serum thyroxine (T4), triiodothyronine (T3), free T4 and free T3 were low, while his thyrotropin was high. He was positive for antithyroglobulin antibodies, antimicrosomal antibodies, and TSH-binding inhibitor immunoglobulins. He was diagnosed as having atrophic thyroiditis. We also determined the HLA haplotypes of his family members. His father's HLA haplotypes were A2, BW61(a) and A24, BW52(b), while his mother's haplotypes were A24, BW52(c) and A30, BW60(d). The HLA haplotypes of both the patient and his younger brother showed a and d, while the patient's elder brother's HLA haplotypes showed b and c. His family members all had normal thyroid function, but his father was positive for antimicrosomal antibodies. In summary, we describe a rare case where the onset of hypothyroidism was prepubertal, where the pathogenesis may have involved TSH-receptor blocking antibodies, and where the inheritance of the disease may have been from the paternal side of the family.

Patients with co-existing hereditary spherocytosis (HS) and UDP-glucuronosyltransferase 1A1 (UGT1A1) deficiency as Gilbert's syndrome (GS) have been reported, and previous studies have demonstrated an increased risk for developing gallstones in patients with co-inheritance of GS and HS. We experienced an interesting case of HS showing persistent jaundice after splenectomy, and upon further evaluation, the 25-year-old female patient was found to have HS combined with UGT1A1 deficiency. Sequence analysis of the UGT1A1 gene revealed that she was a compound heterozygote with p.[G71R; Y486D] + [Y486D] mutations, which suggests Crigler-Najjar syndrome type II rather than GS. Careful evaluation of inappropriately elevated bilirubin level compared with the degree of hemolysis is important, reflecting the therapeutic implication of splenectomy and cholecystectomy.