Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride.

Nephrogenic diabetes insipidus (NDI) is characterised by the inability of the kidney to concentrate urine in response to arginine vasopressin. The consequences are severe polyuria and polydipsia, often associated with hypertonic dehydration. Intracerebral calcification, seizures, psychosomatic retardation, hydronephrosis, and hydroureters are its sequelae. In this study, four children with NDI were treated with 3 mg/kg/day hydrochlorothiazide and 0.3 mg/kg/day amiloride orally three times a day for up to five years. While undergoing treatment, none of the patients had signs of dehydration or electrolyte imbalance, all showed normal body growth, and there was no evidence of cerebral calcification or seizures. All but one had normal psychomotor development and normal sonography of the urinary tract. However, normal fluid balance was not attainable (fluid intake, 3.8-7.7 l/m2/day; urine output, 2.2-7.4 l/m2/day). The treatment was well tolerated and no side effects could be detected. Prolonged treatment with hydrochlorothiazide/amiloride appears to be more effective and better tolerated than just hydrochlorothiazide. Its efficacy appears to be similar to that of hydrochlorothiazide/indomethacin but without their severe side effects.     

A novel AVPR2 missense mutation in a Chinese boy with severe inherited nephrogenic diabetes insipidus

Inherited nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to arginine vasopressin (AVP). The most common cause is mutations in the AVP receptor 2 (AVPR2) gene at Xq28. Severe complications of NDI are rare but can occur after severe dehydration without treatment. A 7-year-old boy presented with short stature and severe intellectual disability other than polyuria and polydipsia. The karyotype was normal. Direct sequencing revealed a novel missense mutation c.506T > C (p.L169P) in AVPR2 in the patient. His mother was heterozygous for the mutation. The mutation was absent in 103 unrelated healthy males and predicted to be consistently pathogenic by several prediction methods, including Polyphen, SIFT, PMut, PhD-SNP, SNPs3D, PANTHER, and MEMPACK. Awareness of the primary signs of NDI, polyuria, and polydipsia would facilitate early diagnosis and treatment to prevent its severe complications. Also, molecular analysis will provide a rapid and definitive diagnosis and facilitate genetic counseling for family planning.     

Characterization of AQP‐2 gene mutation (R254Q) in a family with dominant nephrogenic DI

We identified the AQP‐2 gene mutation (R254Q) in a family with dominant NDI. The patient studied here has NDI with partial response to the anti‐diuretic effect of AVP and dDAVP. Hereditary NDI seems to have the uniform clinical manifestations, but this might only reflect the information on screened patients with clear clinical presentations. It may be that a milder form of NDI has been overlooked due to a lack of genetic identification. Gene mutation analysis should be considered even in patients with mild NDI symptoms. Fortunately, both V2R and AQP2 genes are small and can be easily analyzed.     

A variant of nephrogenic diabetes insipidus: V2 receptor abnormality restricted to the kidney

In congenital nephrogenic diabetes insipidus (NDI) blunted responses of plasma factor VIII, von Willebrand factor, and plasminogen activator to the synthetic V₂ analogue 1-desamino-8-d-arginine vasopressin (DDAVP) have been reported. In addition, vasodilatory responses to DDAVP appear to be absent in NDI. We describe a boy, who presented shortly after birth with the typical features of NDI, but who showed normal coagulation, fibrinolytic and vasodilatory responses to DDAVP. We conclude that in this patient the defect is confined to the kidney, while in other NDI patients there may be a general V₂ receptor abnormality. These findings point to heterogeneity in NDI.     

Nephrogenic Diabetes Insipidus and Dwarfism: Rare Combination in a Female Patient

A young girl with perinatal history of breech presentation and Caesarian section delivery exhibited symptoms of diabetes insipidus and marked shortness of stature. Possibility of anti-diuretic hormone and growth hormone deficiencies was ruled out completely by extensive endocrinological studies, which instead demonstrated the existence of nephrogenic diabetes insipidus (NDI) in this patient. Turner's syndrome was denied by normal female karyotype. Her dwarfism could not be explained by other causes than NDI. Review of the literature, however, shows that combination of NDI and dwarfism is extremely rare condition in a female case of the disease.     

Familial mitochondrial encephalopathy with fetal ultrasonographic ventriculomegaly and intracerebral calcifications

In two sibs antenatal ultrasonography revealed identical intracranial calcification, ventricular widening and microcephaly. The first pregnancy was artificially terminated at 19 weeks. Post-mortem examination of the brain revealed destructive calcification and extracerebral neuronal heterotopia. The second sib went to term but died 48 h after birth from irreversible lactic acidosis. Autopsy showed extensive encephalopathy with cavitation and calcification in the cerebral hemispheres, polymicrogyria, multiple neuronal heterotopia, partial callosal dysgenesis, and severe Leigh syndrome, together forming a continuum of early and late brain disruption. Mitochondrial respiratory chain abnormalities, mainly affecting complexes I and IV, and deficiency of pyruvate dehydrogenase complex were detected in skeletal muscle and in liver. A normal functioning of the respiratory chain was found in the fibroblasts. Analysis of mtDNA from muscle, liver and blood revealed normal amounts of intact mtDNA without any of the known point mutations associated with MELAS, MERRF or Leigh syndromes. The early fetal disruption and necrotic changes in the brains of sibs indicate a specific genetically determined disorder which affects neuronal migration, a finding not previously associated with respiratory chain disorders. The present disorder may mimic antenatal congenital infectious encephalopathy because of the combined finding of microcephaly and destructive intracerebral calcification.     

Neurodevelopmental impairment at 2 years of age in children born before 29 weeks’ gestation with bronchopulmonary dysplasia

IntroductionVery preterm children are at a high risk for neurological impairment, especially those with bronchopulmonary dysplasia (BPD). The main goal of this study was to describe the neurodevelopmental impairment (NDI) at 2 years of corrected age in children born before 29 weeks’ gestation between 2010 and 2015 and affected by BPD at 28 days of life. We also searched for risk factors associated with NDI, especially postnatal steroid (PNS) administration.Material and methodsThis was a retrospective study comprising a cohort of children hospitalized at the university hospital in Grenoble, born before 29 weeks’ gestation between 2010 and 2015, and included in the monitoring network “Naitre et Devenir” (RND). Infants at 2 years of corrected age were classified as having NDI if they had at least one of the following outcomes: a global developmental quotient (DQ) on the revised Brunet–Lézine scale of < 85, blindness, deafness, or cerebral palsy (CP) graded as level 3 or more according to the Gross Motor Function Classification System.ResultsA total of 129 children were included, of whom 99 were monitored at the age of 2 years: 31.3% of the population had NDI and 4% had CP. The median DQ test result was 90 (interquartile 82–97). Factors associated with NDI in univariate analysis were low gestational age, low birth weight, a cord pH < 7.2, chorioamnionitis, treatment for persistent ductus arteriosus, longer oxygen therapy, and outborn status, which almost reached statistical significance. In multivariate analysis, low gestational age and outborn status remained statistically significant, while chorioamnionitis was found to have some association with NDI. While 13.1% of the followed-up population was treated with PNS, this risk factor was not associated with NDI.ConclusionIn a population of very preterm children, one third had NDI at 2 years of corrected age. Low gestational age, outborn status, and perinatal inflammation are associated with this unfavorable outcome. The frequency of sequelae confirms the importance of following up these children.     

Hereditary Nephrogenic Diabetes Insipidus Type-2

Nephrogenic diabetes insipidus (NDI) in a fetus in utero was suspected because of the family history, and evidence of increased amniotic fluid by echosonography. The mother's karyo-type was 46 XX/47 XXX. After birth, the patient was diagnosed as NDI type-2 which is partially resistant to antidiuretic hormone.     

Calcification of the gastric mucosa associated with tumor lysis syndrome in a child with non-Hodgkin lymphoma

Tumor lysis syndrome (TLS) is an important complication associated with hematological malignancies leading to increased morbidity and mortality. Metastatic calcification due to calcium phosphate crystals precipitated in soft tissues is rarely encountered in TLS. We describe a child with non-Hodgkin lymphoma who had gastric mucosal calcification related to severe hyperphosphatemia due to TLS. Upper-gastrointestinal endoscopic examination performed because of abdominal complaints revealed diffuse mucosal white lesions in mucosa of the gastric antrum and corpus. Pathological examination of the mucosa of the gastric corpus showed marked calcification in the lamina propria. We suggest that calcification in mucosa of the gastric corpus may be seen in patients with TLS. We also suggest that gastric mucosal calcifications should be considered in patients with hematological malignancies from TLS.     

The effect of exogenous 3':5'-adenosine monophosphate on urinary output in children with vasopressin-resistant diabetes insipidus.

The administration of c-AMP and DB c-AMP to six children with NDI has failed to yield an antidiuretic effect. From the present study it may be concluded that, at the doses used, neither c-AMP nor its dibutyryl derivative can mimic the action of ADH in NDI as they do in normal subjects. On the contrary, DB c-AMP increased urine volume and Cosm in a very marked way, without changing the creatinine excretion.     

Myocardial calcifications in infants with congenital heart disease

Summary A histopathologic study of six hearts from infants with congenital heart disease and myocardial calcification revealed that foci of calcification were surrounded by normal-appearing myocardial tissue, ischemic myocardial tissue, or both. Inflammatory process, necrotic tissue removal process, and scar formation were not identified in the majority of these subjects. Three congenital heart anomalies are newly reported as associated with myocardial calcifications. The results of this study give evidence that necrotic tissue in the myocardium of some infants tends to become calcified rather than be removed and scarred as occurs in the adult. It also confirms that prenatal cardiac disease and trauma such as surgery might account for the presence of myocardial calcification.     

A rare lethal case of chondrodysplasia punctata with extensive airway involvement

Stippled cartilaginous calcification, an important radiologic sign, is described as 'chondrodysplasia punctata' when seen in association with limb shortening and maxillofacial hypoplasia. We report chondrodysplasia punctata in a male neonate who presented with limb shortening, midfacial hypoplasia, and laryngeal stenosis leading to death within a few minutes of birth. A post-mortem radiograph revealed generalized punctate calcification of cartilaginous structures, including airways, rib ends, spine, long bone epiphyses, tarsus and pinna, and brachytelephalangy.     

A Novel Mutation of the Arginine Vasopressin Receptor 2 Gene in a Patient with Congenital Nephrogenic Diabetes Insipidus

We have identified a novel mutation of the arginine vasopressin receptor 2 (AVPR2) gene in a case of congenital X-linked nephrogenic diabetes insipidus (NDI). The patient was a 2-mo-old Japanese boy with persistent fever and failure to thrive. He was diagnosed as having congenital NDI by clinical and laboratory findings. Molecular analysis demonstrated that he was hemizygous for a G to C transversion in exon 2 of the AVPR2 gene which resulted in a glycine to arginine substitution (G107R) at the 107th codon of the first extracellular loop. His mother was heterozygous for the same mutation. We speculated that the G107R mutation would interfere with the binding capacity of the AVPR2, since G107R is located near F105 and R106, both of which are crucial for ligand binding. In cases of X-linked NDI, mutations in the AVPR2 gene are distributed widely. Thus, DNA analysis throughout the gene is of clinical value for the identification of female carriers, and it also gives precise information for genetic counseling.     

Idiopathic Fanconi's syndrome with nephrogenic diabetes insipidus in a child who presented as vitamin D resistant rickets--a case report and review of literature

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and a child mainly presents with dehydration and hypernatremia. We report the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus (NDI) in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi's syndrome. We hypothesized that the NDI may be due to severe hypokalemia induced tubular dysfunction. The child was treated for hypophosphatemic rickets with severe metabolic acidosis and the treatment for NDI was also given. Now he has healed rickets and normal blood pH, sodium and osmolarity.     

Intramuscular hemangioma of the temporalis muscle with incidental finding of bilateral symmetric calcification of the basal ganglia: a case report

We report an 11-year-old boy whose brain computed tomography findings incidentally revealed bilateral basal ganglia calcification. He was symptom-free and had no abnormal neurological findings. He was diagnosed with Fahr's disease based on radiological findings and after excluding other etiologies such as infection, metabolic disorders, congenital malformation and malignancies. Most of the reported cases display an autosomal dominant mode of inheritance. Although Fahr's disease is a rare cause of basal ganglia calcification in children, this disease should be considered in children with a family history of neuropsychiatric disorders.     

Acute bursitis calcarea trochanterica in an infant,with perforation into the hip joint demonstrated by arthrogram

A case of bursitis calcarea trochanterica acuta is reported in a boy aged four months. The calcification was amorphous, and arthrography revealed extension into the hip joint. The lesion was treated surgically.     

超低和极低出生体重儿神经发育结局及影响因素分析

目的 评估超低/极低出生体重儿 （ELBWI和VLBWI） 在纠正年龄 （CA） 18月时神经发育结局,探讨影响神经发育结局的因素。方法 收集2013年1月至2014年6月入住新生儿重症监护病房并存活出院的ELBWI和VLBWI病例,在CA40周、1、3、6、12、18月定期随访,评估神经发育结局。按神经发育状况分为神经发育正常组和神经发育异常组,比较两组临床资料的差异,分析ELBWI和VLBWI神经发育的危险因素。结果 共338例ELBWI和VLBWI纳入研究,15例在住院期间死亡。CA18月时,145例 （44.9%） 存活且随访资料完整,75例 （23.2%） 死亡,失访103例 （31.9%）。CA18月时,145例患儿中神经发育损伤71例 （49.0%）,3例 （2.1%） 脑性瘫痪;未发现单眼或双眼失明的视觉损伤及需要助听器的听觉损伤。Logistic回归分析发现BPD和败血症是ELBWI和VLBWI神经发育异常的独立危险因素 （OR=3.530,P < 0.001;OR=2.528,P=0.035）,BPD发生程度越重,神经发育异常的发生率越高。结论 败血症、BPD （尤其是重度BPD） 是ELBWI和VLBWI神经发育异常的危险因素。     

Coronary artery calcification in Kawasaki disease

To evaluate the angiographic features of coronary lesions in Kawasaki disease with coronary artery calcification, cinefluoroscopy and cineangiography were retrospectively reviewed in 116 patients who had undergone coronary angiography between 1982 and 1989. Angiographic abnormalities of coronary arteries were demonstrated in 55 of the 116 patients. In 5 (9.1%) of the 55 patients, 9 with calcification were identified by cinefluoroscopy and chest x-ray. Eight of the 9 calcified lesions showed a circular or ring-shape configuration. Coronary angiography revealed a total occlusion of the right coronary artery with collateral circulation from the distal left coronary artery in 2 patients and a severe stenosis of the right coronary artery in 2 patients, in whom anticoagulant therapy had not been continued during the follow-up periods. The remaining patient in whom anticoagulant therapy had been continued had bilateral aneurysms but no significant stenosis. These results indicate that a ringshape calcification on chest x-ray in a patient with a history or Kawasaki disease may suggest an involvement by coronary artery stenosis even when anticoagulant drugs had been given. Therefore, coronary angiography should be performed to evaluate the stenotic lesions if this type of calcification is found by routine radiographic examination.     

Grade and laterality of intraventricular haemorrhage to predict 18-22 month neurodevelopmental outcomes in extremely low birthweight infants

Aim: To determine whether extremely low‐birthweight (ELBW) infants with bilateral compared to unilateral intraventricular haemorrhage (IVH) have worse neurodevelopmental outcomes at 18–22 months. Methods: A total of 166 ELBW infants (<1000 g) admitted to a Cincinnati NICU from 1998 to 2005 with a head ultrasound showing Grade I–IV IVH and neurodevelopmental assessment at 18–22 months corrected age were included. Multivariable linear and logistic regression models were developed to determine the impact of laterality and grade of IVH and other clinical variables to predict scores on the Bayley Scales of Infant Development, Second Edition, Mental Development Index and Psychomotor Development Index and the combined outcome of neurodevelopmental impairment (NDI). Results: Infants with bilateral grade IV IVH had lower adjusted mean Bayley scores compared with infants with unilateral grade IV IVH. For grades I, II and III IVH, bilaterality of IVH was not associated with lower mean Bayley scores. Infants with grade IV IVH had the highest odds of NDI. The probability of NDI increased with sepsis and postnatal steroid use. Conclusion: ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I–III IVH had similar outcomes whether they had unilateral or bilateral IVH.