Familial glucocorticoid deficiency, alacrimia and achalasia—Allgrove syndrome

We report three brothers with Allgrove syndrome. All three had evidence of adrenal insufficiency and deficient tear production, though neither of them had achalasia, the third component of the disorder at the time of this report. Neurological abnormalities were present in the index case. The younger siblings were neurologically normal. The familial association of achalasia, alacrimia and adrenal insufficiency, rather than being fortuitous, is a distinct clinical entity.     

Transient erythrophagocytosis in Diamond-Blackfan anemia

We report on a 4-month-old Japanese infant girl with Diamond-Blackfan anemia (DBA) as shown by congenital macrocytic pure red cell hypoplasia with marked reduction of erythroid precursors in bone marrow, reticulocytopenia, increased fetal hemoglobin, and elevated adenosine deaminase activity in peripheral blood. She responded poorly to conventional doses of corticosteroids, however, with high-dose corticosteroids she responded with reticulocytosis and an elevation of hemoglobin level above 12 g/dL. Erythrophagocytosis was noted during the tapering period of prednisone when her hemoglobin level declined to 7.6 g/dL and reticulocyte level to 0.4%. At that time, the erythrophagocytosis was noted in about 60% of marrow histiocytes. These findings were not observed prior to or during the high dose prednisone therapy. We speculate that one of the causes of pure red cell aplasia and reticulocytopenia in DBA is mediated by erythrophagocytosis.     

Familial non-immune hydrops fetalis and congenital pulmonary lymphangiectasia

We report on three siblings with non-immune hydrops fetalis. Congenital pulmonary lymphangiectasia was diagnosed in two of them. One of these, a girl still alive and suffering from frequent airway infections, has bilateral pleural effusions and distal congenital lymphoedema. Conclusion To our knowledge, this is the first report of non-immune hydrops fetalis and congenital pulmonary lymphangiectasia occurring in siblings. Received: 4 February 1997 and in revised form: 23 September 1997 / Accepted: 23 September 1997     

Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness

Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition. We now report two brothers of consanguineous Palestinian parents, whose lymphadenopathy, lymph node histology, and polyclonal hypergammaglobulinemia indicated RDD. The presence of intrauterine fractures, short stature, and sensorineural hearing impairment suggested a rare familial form of the disorder. Moynihan et al. recently described a Pakistani family with a familial histiocytic disorder highly reminiscent of the brothers reported here, whose lymph node morphology was apparently consistent with RDD as well. The presence of sensorineural deafness, short stature, and joint contractures, however, suggested a separate, rare autosomal recessive syndrome referred to as Faisalabad histiocytosis, after the family's place of origin. We believe that the brothers described here represent a second family with Faisalabad histiocytosis, which mimics RDD histologically.     

Severe autoimmune hemolytic anemia after unrelated umbilical cord blood transplant for familial hemophagocytic lymphohistiocytosis: significant improvement after treatment with rituximab

A 4-month-old girl diagnosed with familial hemophagocytic lymphohistiocytosis underwent a matched unrelated, umbilical cord blood transplant. Six weeks later she developed severe acute autoimmune hemolytic anemia and thrombocytopenia requiring multiple transfusions. This was refractory to high-dose steroid and intravenous immunoglobulin, but did respond to Rituximab (anti-CD20 monoclonal antibody) 375 mg/m2. Hemolysis recurred after steroid tapering but responded to a second course of Rituximab. This case report highlights the difficulty in managing posttransplant autoimmune hemolytic anemia.     

Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. Conclusion A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension. Received: 12 June 1998 and in revised form: 13 October 1998 and 21 December 1998 / Accepted: 10 January 1999     

Association of Severe Microcephaly, Short Palpebral Fissures, Micrognathia, Growth Retardation and Early Death: A New Syndrome

Four siblings presenting a combination of severe microcephaly, short and laterally downward slanting palpebral fissures, hypertelorism, micrognathia, and growth retardation are reported. The proband had congenital heart disease complicating these characteristic symptoms. The parents were not consanguineous. The karyotypes of the proband and parents were normal. The faces of three brothers of the proband were very much like that of the proband, but tvjo of them had cleft palates. Although it was confirmed that one of the three brothers did not have congenital heart disease, its presence in the other two could not be ascertained. All three older brothers died within one month after birth.     

Hemophagocytic Syndrome with Restricted Organ Involvement: Excessive Hemosiderosis and Fibrosis of the Spleen

We report the case history of a 6 1/2-month-old girl with a hemophagocytic syndrome, pancytopenia, and excessive hepatosplenomegaly. Some extraordinary histological features present in this case—restricted organ involvement, excessive hemosiderosis, and fibrosis of the spleen—further contributed to the well-known problem of distinguishing between infection-associated hemophagocytic syndrome and familial hemophagocytic lymphohistiocytosis.     

Gillespie syndrome: 2 familial cases]

We report 2 familial cases of Gillespie syndrome in an 8-year-old girl and her brother 16 months old. They had both congenital aniridia, cerebellar ataxia and mental retardation. In the girl, pupillar dilation in the 2 eyes and delay in different milestones development were elicited at 2 years. She was summoned at the birth of her brother that had pronounced floppiness and the same ocular abnormalities. Ophtalmological exam confirmed partial and bilateral aniridia in both sibs. Brain MRI showed vermis atrophy in the girl and an hypoplasic inferior vermis in her brother. Apropos of these case reports, we make a brief update about this extremely rare genetic syndrome.     

纤维支气管镜下带囊支架置入术治疗儿童气管狭窄2例

目的:通过纤维支气管镜下带囊支架置入术治疗儿童气管狭窄,观察近期疗效和并发症。方法:例1,女,4月龄,因“发现心脏杂音3个月余,咳嗽10 d渐加重,伴发热、喘息3 d”入院,诊断为膜周部+肌部室间隔缺损,房间隔缺损（继发孔型）,肺动脉高压,主气道下段及左右主支气管变形狭窄。行肺动脉环缩术,房间隔、室间隔缺损修补术+主动脉悬吊术成功后,术后2个月内3次撤离呼吸机均未成功。例2,女,1岁10个月,因“咳嗽1个月余”入院,诊断为左主支气管狭窄,EBV相关性噬血细胞淋巴组织细胞增生症。左侧支气管狭窄致使排痰困难,肺部反复感染,左肺气肿。2例患儿家长在充分了解纤维支气管镜下带囊支架置入术可能的风险后签署知情同意书。采用“边麻边进”方法行气道黏膜表面麻醉,例1和例2 选择带囊支架长度分别为24和29 mm,直径均为4 mm（均经雷帕霉素处理）,由支架导入器送入纤维支气管镜,在纤维支气管镜直视下释放带囊支架,然后退出支架导入器。结果:2例患儿置入带囊支架后狭窄段气管扩张良好,带囊支架放置2~3个月随访,未见肉芽组织增生等并发症。结论:纤维支气管镜下带囊支架置入术治疗气管狭窄近期疗效较好,远期疗效尚待观察。     

Successful Pulmonary Embolectomy in a 4-Year-Old Girl with Antithrombin III Deficiency

We report the case of a 4-year-old girl, successfully treated by surgical pulmonary embolectomy for acute massive pulmonary embolism. She was known to have a congenital antithrombin III deficiency diagnosed after a familial history of thromboembolic events. Surgical embolectomy may be considered as a treatment option in selected patient with anatomically extensive pulmonary embolism.     

A familial case of Rothmund-Thomson syndrome. A case in favor of the uniqueness of the syndrome. Association with osteosarcoma

A 7 years old girl with Rothmund-Thomson syndrome is described. A detailed study of the dermatologic lesions has been performed. The parent's girl are first cousins and one of her brothers, also having the Rothmund-Thomson syndrome, died from an osteosarcoma of the tibia at the age of 11. This familial observation gives support to the uniqueness of the Rothmund-Thomson syndrome with autosomal recessive inheritance.     

PFAPA syndrome in siblings. Is there a genetic background?

“PFAPA syndrome” is an autoinflammatory entity composed of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. There have been many reports of children with the disease, but only occasionally have been described in siblings, and no specific genetic mutation has been determined yet. Corticosteroids are the mainstay in the treatment of the acute attacks. The role of surgery in long-term follow-up (tonsillectomy with or without adenoidectomy) is controversial. We report two brothers affected with the syndrome, in whom corticosteroids as the only treatment led to an improvement. A genetic work-up was performed, making very unlikely other possible syndromes of recurrent fever. Conclusion: PFAPA syndrome is the most common recurrent periodic fever disorder described in childhood. Its genetic background has not been elucidated yet. Our contribution with two siblings affected with PFAPA syndrome further support the genetic basis for the entity.     

Massive hemoperitoneum with splenic infarction in Evans syndrome

Evans syndrome is a very rare hematologic autoimmune disease, characterized by a direct Coombs' positive hemolytic anemia and immune thrombocytopenic purpura without a known underlying etiology. The clinical course is generally chronic with frequent relapses and remissions. Evans syndrome usually is complicated by hemolytic or thrombocytopenic symptoms. This is seldom associated with thrombosis or infarction. Reported here is a case with massive hemoperitoneum because of splenic infarction with rupture, in an 18-month-old male patient with Evans syndrome, and the embolization of splenic artery. This article also carries clinical and imaging features and the review of medical literature.     

Hepatocellular carcinoma in Alagille's syndrome: a family study

Alagille's syndrome is a common form of familial intrahepatic cholestasis. In addition to the hepatobiliary system, many other organ systems are affected. Most of the affected patients survive through adulthood. Hepatic involvement is the cause of death in about one-third of patients. Hepatocellular carcinoma complicating the course of this disease is very rare and has been reported previously in only three cases. We report a family in which three of four siblings with this syndrome developed hepatocellular carcinoma and died as a result of it. None of these children had a liver disease, other than Alagille's syndrome, that could account for the development of such a tumor. This experience suggests that Alagille's syndrome, or at least chronic cholestasis, may be a predisposing factor for the development of hepatocellular carcinoma. Annual determination of alpha-fetoprotein and abdominal computed tomography (CT) scan may detect the development of a hepatocellular carcinoma in such cases while they are still resectable.     

Familial liability to complications after BCG vaccination

Abstract Adverse reactions induced by vaccination with bacille Calmette-Guerin (BCG) were observed in three infants from two blood-related families. A boy and a girl showed disseminated BCG infection with a fatal course in the former case. The third infant had regional suppurative lymphadenitis. Cases of two other children from the same families are also described: a boy who received BCG vaccine after 5 y of age without complications, and a girl who has not yet been vaccinated. The clinical course and immunological evaluation of the reported cases suggest a congenital immunodeficiency of an unusual transient nature. The role of genetic factors in familial susceptibility to mycobacterial infection also needs to be taken into consideration.     

Hydrocephalus combined with congenital cataract and microphthalmia

We describe a case of bilateral microphthalmia with bilateral congenital cataracts associated with hydrocephalus in a 9-month-old girl with consanguineous parents. The differential diagnosis included: (1) congenital rubella syndrome; (2) congenital toxoplasmosis; (3) chromosome alterations; and (4) metabolic disease. However, negative clinical, laboratory, and instrumental investigations excluded all of these hypotheses. We stress the usefulness of echography in establishing whether or not infection has occurred during intrauterine life.     

Familial isolated congenital asplenia: a rare,frequently hereditary dominant condition,often detected too late as a cause of overwhelming pneumococcal sepsis. Report of a new case and review of 31 others

Congenital isolated asplenia may arise as a minor form of situs abnormalities or result from an unrelated specific defect of spleen development. It is a rare life-threatening condition and pneumococcal sepsis is often the first sign of the disease. We report on the case of a deceased 11-month-old girl and her father who developed recurrent pneumococcal meningitis. The fatal evolution in the girl was due to Streptococcus pneumoniae serotype 23 with intermediate penicillin sensitivity 4 h after amoxicillin (100 mg/kg i.v.) administration. Establishing the diagnosis of congenital isolated asplenia in the case of pneumococcal sepsis can be achieved by performing two easy and non-invasive investigations: searching for Howell-Jolly bodies on blood smears and performing ultrasound examination of the abdomen to look for the spleen. In the case of congenital isolated asplenia, use of appropriate prophylaxis could save the lives of affected children. Our review of the literature yielded 31 cases of congenital isolated asplenia. Thirteen were sporadic and 18 were familial cases involving eight families. CONCLUSION: in the case of Streptococcus pneumoniae sepsis, a systematic search for Howell-Jolly bodies on blood smears and ultrasound examination of the abdomen for the presence of asplenia should be mandatory to detect isolated congenital asplenia. If asplenia is found, potentially life-saving antibiotic prophylaxis and pneumococcal vaccination should be initiated.     

Congenital erythroid and myeloid hypoplasia terminating myelodysplastic syndrome

We describe a 4-month-old infant girl with congenital erythroid and myeloid hypoplasia who developed myelodysplastic syndrome. Bone marrow examination showed severe erythroid and myeloid hypoplasia without dysplastic morphology. Flow cytometry detected autoantibodies to myeloid cells, indicating a diagnosis of Diamond-Blackfan anemia with autoimmune neutropenia. The patient was administered prednisolone and rituximab, which brought the neutrophil count and hemoglobin level to within the normal range. However, bicytopenia recurred at the age of 22 months. She was diagnosed with myelodysplastic syndrome because of trilineage dysplasia and the clonal abnormality of 46,XX,dup(1)(q21;q32) in bone marrow. She was transplanted with cord blood from an unrelated human leukocyte antigen-matched donor and has since remained in complete remission for 20 months.     

Fatal lymphoproliferative disease as a complication of Evans syndrome

A 9-month-old boy had bruising and petechiae. Investigation revealed a Coombs-positive hemolytic anemia and immune-mediated thrombocytopenia. The infant was treated with intravenous immunoglobulin and steroids. The infant eventually had recurrent fevers, hepatosplenomegaly, pulmonary nodules, and parenchymal central nervous system (CNS) lesions develop. Results of a lung biopsy revealed a polyclonal lymphoproliferative disease. Polymerase chain reaction analysis showed the presence of the Epstein-Barr (EB) viral genome in the lung nodules. The infant died from progressive lung disease 6 months after the initial symptoms of Evans syndrome. Lymphoproliferative disease is known to occur in a variety of settings after immunosuppression, especially in solid organ transplant recipients. We report a case of polyclonal lymphocyte proliferation in a patient with Evans syndrome.