A girl with a mutation of the ciliary gene CC2D2A presenting with FSGS and nephronophthisis.

Mutations in the ciliary gene TTC21B, NPHP4, and CRB2 cause familial focal and segmental glomerulosclerosis (FSGS). We report a girl with a mutation of the ciliary gene CC2D2A presenting with FSGS and nephronophthisis. The patient had mental retardation, postaxial polydactyly, and ataxic breathing, and was diagnosed as having compound heterozygous CC2D2A missense mutations at age 5. Retrospectively, azotemia at 1 year and proteinuria at 5 years were recorded but not investigated. At age 6, she was referred to the pediatric nephrology service because of hypertension, pretibial pitting edema, heavy proteinuria, and hematuria. eGFR was 66 ml/min/1.73 m2, total protein 5.3 g/dl, albumin 2.4 g/dl, and cholesterol 317 mg/dl. Ultrasonography showed normal-sized kidneys with a cyst in the right. Losartan was started. On renal biopsy, 8 out of 24 glomeruli were globally sclerosed, and three showed segmental sclerosis and/or hyalinosis with no immune deposits. Mild tubular dilatation, tubular atrophy, and interstitial fibrosis were observed. On electron microscopy, glomeruli showed focal foot process effacement with no electron dense deposits. Since losartan did not exert an obvious effect, treatment with prednisolone was tried. Urine protein decreased from 6.6 to 3.7 g/gCr. Prednisolone was discontinued after 10 days, however, because she developed duodenal ulcer perforation that necessitated omentoplasty. Subsequently, she was treated with losartan only. Her renal function deteriorated and peritoneal dialysis was initiated 8 months later. FSGS in this patient could be primary glomerular associated with CC2D2A mutation, rather than the consequences of tubulointerstitial fibrosis.

Neonatal Linear IgA Bullous Dermatosis Mediated by Breast Milk-Borne Maternal IgA.

IMPORTANCE: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disease that can be fatal when associated with respiratory failure. All previously reported cases of neonatal LABD have been in newborns with healthy asymptomatic mothers, and the pathogenic IgA was of unknown origin. OBJECTIVE: To clarify the origin of IgA associated with LABD in neonates born of healthy asymptomatic mothers. DESIGN, SETTING, AND PARTICIPANTS: This case study analyzed the laboratory findings of a single breast-fed newborn male with neonatal LABD admitted to the Keio University Hospital in Tokyo and his healthy asymptomatic mother. The healthy newborn developed life-threatening blisters and erosions of the skin and mucous membranes on day 4 after birth. Blood serum, skin, and maternal breast milk were examined for IgA autoantibodies. MAIN OUTCOMES AND MEASURES: Histopathologic and immunofluorescence analyses of specimens (serum, skin, and breast milk) from the patient and his mother. RESULTS: Histopathologic evaluation of the newborn's skin revealed subepidermal blisters with neutrophil infiltrates, and immunofluorescence testing showed linear IgA deposition along the basement membrane zone (BMZ), which lead to the diagnosis of neonatal LABD. Indirect immunofluorescence using normal human skin after treatment with 1-mol/L sodium chloride showed the patient to have circulating IgA binding to the dermal side of BMZ. Immunohistochemical staining proved the deposition of secretory IgA in the neonatal skin by demonstrating the presence of J chain-not been seen in other LABD cases-indicating that the autoantibodies producing the blisters were derived from the maternal breast milk. Although no circulating IgA against the skin was detected in mother's sera, the breast milk contained IgA that reacted with the dermal side of the BMZ. No new blister formation was observed after cessation of breastfeeding. CONCLUSIONS AND RELEVANCE: The results of this case study suggest a passive transfer of pathogenic IgA to a newborn from an asymptomatic mother via breast milk. In prior reports, no serum from asymptomatic mothers of newborns with LABD had IgA autoantibodies binding to skin components; however, in this case, we found that the maternal breast milk contained IgA autoantibodies associated with neonatal LABD. In neonatal LABD, maternal breast milk should be examined for IgA autoantibodies and breast milk feeding should be discontinued as soon as neonatal LABD is suspected.

Tubular dysfunction in extremely low birth weight survivors.

BACKGROUND: Extremely low birth weight (ELBW) survivors may develop glomerulosclerosis due to low nephron number, whereas their tubular function remains unknown except for hypercalciuria and phosphaturia. METHODS: Fifty-three subjects (30 boys and 23 girls, aged 7 months-19 years, median 36 months) were studied retrospectively. The median gestational age and birth weight were 26 weeks (range 22-32) and 745 g (range 316-999), respectively. Urine calcium-to-creatinine ratio (Ca/Cr), N-acetyl-ß-D-glucosaminidase-to-creatinine ratio (NAG/Cr), ß2 microglobulin-to-creatinine ratio (ß2m/Cr), uric acid-to-creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin-to-creatinine ratio (malb/Cr) were examined. We also assessed the association between urine parameters and current age, gestational age, birth weight, and predictors of renal injury. Follow-up data were analyzed in 43 subjects 4-6 years later. RESULTS: Ninety percent of subjects had at least one tubular dysfunction. Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, ß2m/Cr 38.2%, malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr, suggesting tubular function maturation. Urine ß2M/Cr and glu/Cr were negatively correlated with the gestational age. There were significant associations between elevated glu/Cr and asphyxia or neonatal acute kidney injury, and elevated NAG/Cr and indomethacin use, although these were not confirmed by multivariate analysis. At follow-up, the frequency of elevated NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr, IgG/Cr, and ß2m/Cr remained similar or increased. CONCLUSION: Tubular dysfunction is common in ELBW survivors. Some abnormalities resolved with age while some remained persistent or even increased.

Trajectory of Estimated Glomerular Filtration Rate Predicts Renal Injury in Children with Multicystic Dysplastic Kidney.

BACKGROUND/AIMS: Children with a solitary functioning kidney have a risk of renal injury caused by hyperfiltration. Timely intervention with renin-angiotensin inhibitors may be beneficial. We examined whether trajectory of estimated glomerular filtration rate (eGFR) would predict renal injury, defined as microalbuminuria/proteinuria, hypertension, and/or a decline in eGFR. METHODS: Seventeen patients (male 7, female 10) with multicystic dysplastic kidney (MCDK; median age 13 years, range 6-19 years) followed in our clinic were examined retrospectively. An eGFR decline was defined as a fall to < 90 mL/min/1.73 m2 or a decline of > 5 mL/min/1.73 m2/year for those with baseline eGFR of ≥90 or < 90 mL/min/1.73 m2 respectively. RESULTS: Nine patients had renal injury at the time of investigation. Compared with 8 patients without renal injury, those with renal injury tended to be older (14.7 ± 4.2 vs. 11.4 ± 4.6 years) and the birth weight was smaller (2,538 ± 281 vs. 2,966 ± 361 g, p < 0.05). The frequency of contralateral congenital anomaly of kidney and urinary tract (cyst, hydronephrosis, or vesicoureteral reflux) were not different. The trajectory of eGFR in those without renal injury was either an increase (n = 3) or unidentifiable (n = 5), whereas that in the renal injury group was exclusively an increase followed by decline (p < 0.05). The average age of the onset of eGFR decline was 9.4 ± 4.2 years and that of the start of renal injury (albuminuria/proteinuria 5, eGFR decline 4, hypertension 1) was 12.5 ± 4.2 years. CONCLUSION: All the children with MCDK who developed renal injury had eGFR trajectory of increase followed by decline. Renal injury followed the peak eGFR by 3 years on average. This observation is in agreement with the hyperfiltration theory and underscores the importance of following eGFR trajectory closely.

Influence of intramolecular f-f interactions on nuclear spin driven quantum tunneling of magnetizations in quadruple-decker phthalocyanine complexes containing two terbium or dysprosium magnetic centers.

Nuclear spin driven quantum tunneling of magnetization (QTM) phenomena, which arise from admixture of more than two orthogonal electronic spin wave functions through the couplings with those of the nuclear spins, are one of the important magnetic relaxation processes in lanthanide single molecule magnets (SMMs) in the low temperature range. Although recent experimental studies have indicated that the presence of the intramolecular f-f interactions affects their magnetic relaxation processes, little attention has been given to their mechanisms and, to the best of our knowledge, no rational theoretical models have been proposed for the interpretations of how the nuclear spin driven QTMs are influenced by the f-f interactions. Since quadruple-decker phthalocyanine complexes with two terbium or dysprosium ions as the magnetic centers show moderate f-f interactions, these are appropriate to investigate the influence of the f-f interactions on the dynamic magnetic relaxation processes. In the present paper, a theoretical model including ligand field (LF) potentials, hyperfine, nuclear quadrupole, magnetic dipolar, and the Zeeman interactions has been constructed to understand the roles of the nuclear spins for the QTM processes, and the resultant Zeeman plots are obtained. The ac susceptibility measurements of the magnetically diluted quadruple-decker monoterbium and diterbium phthalocyanine complexes, [Tb-Y] and [Tb-Tb], have indicated that the presence of the f-f interactions suppresses the QTMs in the absence of the external magnetic field (H(dc)) being consistent with previous reports. On the contrary, the faster magnetic relaxation processes are observed for [Tb-Tb] than [Tb-Y] at H(dc) = 1000 Oe, clearly demonstrating that the QTMs are rather enhanced in the presence of the external magnetic field. Based on the calculated Zeeman diagrams, these observations can be attributed to the enhanced nuclear spin driven QTMs for [Tb-Tb]. At the H(dc) higher than 2000 Oe, the magnetic relaxations become faster with increasing Hdc for both complexes, which are possibly ascribed to the enhanced direct processes. The results on the dysprosium complexes are also discussed as the example of a Kramers system.