Galactosemia—A clinical and enzymological study in a family

Summary A case of galactosemia, proved by erythrocyte galactose-1-phosphate uridyl transferase studies, apart from a suggestive family history, typical clinical picture and other supportive investigations, has been reported. Both the parents were first cousins. The parents and one younger sibling of the patient had heterozygous enzyme levels. The patient showed some improvement on a modified Holzel's diet but later deteriorated and died due to hepatic failure resulting from continued but unwitting administration of galactose. Cr⁵¹ studies demonstrated markedly reduced red cell life span. The autosomal recessive nature of the galactosemia trait has been brought out. The diagnostic criteria are reviewed and the importance of enzyme studies as a confirmatory investigation is stressed. From the Department of Pediatrics, K.G. Medical College and Central Drug Research Institute, Lucknow.     

Dermatoglyphics in Saethre-Chotzen syndrome: a family study

The dermatoglyphic findings in a Cuban family with the Saethre-Chotzen syndrome are reported. The family consisted of the parents who were first cousins and their three children. A new classification of zygodactylous patterns was used. Characteristic dermatoglyphic patterns which appeared in these cases were representative of the syndrome. Dermatoglyphics also helped to discover minor expressions of syndactyly and showed that all the members of the family had zygodactylous patterns on palms and soles.     

Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: enzymological and clinical aspects

BACKGROUND: Inosine 5'-monophosphate dehydrogenase (IMPDH; EC1.1.1.205) catalyzes the rate-limiting step in guanine nucleotide biosynthesis, and may play an important role in treatment of patients with antipurines. METHODS: We used an HPLC method to measure the IMPDH activity in peripheral blood and bone marrow mononuclear cells (MNC). IMPDH activities were determined in children who were diagnosed with and treated for acute lymphoblastic leukemia (ALL), and in a group of control children. RESULTS: The median IMPDH activity for control children was 350 pmol/10(6) pMNC/hr (range 97-896; n = 47). No gender or age differences were observed. IMPDH activity at diagnosis of ALL was correlated with the percentage of peripheral blood lymphoblasts (r = 0.474; P < 0.001; n = 71). The median IMPDH activity at diagnosis was 410 pmol/10(6) pMNC/hr (range 40-2009; n = 76), significantly higher than for controls (P = 0.012). IMPDH activity significantly decreased after induction treatment, and during treatment with methotrexate (MTX) infusions (median 174 pmol/10(6) pMNC/hr; range 52-516; n = 21). The activity remained low during maintenance treatment with 6-mercaptopurine (6MP) and MTX, at a significantly lower level than for controls (P < 0.004). One year after cessation of treatment IMPDH activity returned to normal values. CONCLUSION: The decrease of IMPDH activity at remission of ALL seems to be at least partly due to the eradication of lymphoblasts with the type 2 isoform of the enzyme.     

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.     

Congenital hepatic fibrosis: a family study

One family with four of seven siblings with congenital hepatic fibrosis is reported. The proband, the only member of this family with symptoms referable to the disease, was hospitalized because of an upper gastrointestinal hemorrhage. He had a presinusoidal type of portal hypertension. The other three siblings had the latent form of congenital hepatic fibrosis. In the family studied, intravenous pyelography and kidney biopsies showed normal results. This condition is possibly an inherited recessive autosomal disease.     

挛缩性蜘蛛指(趾)综合征一家系临床及FBN2基因变异分析

目的分析挛缩性蜘蛛指(趾)综合征的临床特征及基因突变特点。方法回顾分析挛缩性蜘蛛指(趾)综合征一家系的临床特点及基因检测结果。结果先证者女,3岁10个月,出生时有蜘蛛样指、双侧肘关节不能活动;父亲、爷爷、曾祖母有同样的表型。先证者及家系中未观察到神经、心血管异常,外耳畸形、听力减退或眼睛异常等。不同性别间的表型及家族成员的表型无显著异质性。提取患儿及其父母、祖父母等外周血DNA行高通量测序,并以Sanger测序进行验证。结果显示先证者FBN2基因错义杂合变异c.244GA(p.Val82Met),先证者父亲、爷爷、曾祖母携带该变异位点。经Alamut功能软件预测,该变异位点可能会影响蛋白结构域功能,按照ACMG变异分类标准,归类为"可能致病性变异"。结论确诊这一挛缩性蜘蛛指(趾)综合征家系的致病基因为FBN2。     

1个非酮性高甘氨酸血症家系的临床和分子遗传学分析

非酮性高甘氨酸血症(NKH)是一种罕见的先天性遗传代谢性疾病,该文报道1例GLDC基因突变所致NKH的中国患儿,就其临床经过、基因缺陷进行研究。患儿以早发性代谢性脑病以及大田原综合征起病,血、尿串联质谱分析均未见异常,颅脑MRI提示胼胝体发育欠佳,脑电图提示爆发抑制。目标基因捕获下代测序结合多重连接探针扩增发现,患儿存在GLDC基因的母源外显子15 c.1786 CT(p.R596X)杂合无义突变及父源外显子4-15大片段杂合缺失,均为明确致病突变,确诊为NKH。经过促肾上腺皮质激素、托吡酯、右美沙芬治疗后,患儿病情无好转,4月龄死亡。NKH临床表型复杂,可通过代谢筛查以及分子遗传学分析获得确诊。     

Neonatal hypertrophic cardiomyopathy: a case report and family study

An infant of a diabetic mother is described with severe neonatal hypertrophic obstructive cardiomyopathy. Commencement of regular intravenous propranolol was associated with marked clinical improvement. Long-term oral propranolol was continued and at 12 months of age there was complete resolution of the cardiomyopathy. Familial hypertrophic cardiomyopathy hypertrophy was present in two other generations of this family. The results of family screening and tissue typing are presented, with the suggestion that tissue typing may be a useful tool in the assessment of doubtful cases in certain affected families.     

Metabolic, enzymological and molecular assessment of mitochondrial cytopathies]

The most important function of mitochondria in all tissues is oxidative phosphorylation namely the oxidation of fuel molecules by the respiratory chain and the concomitant energy transduction into ATP. A disorder of the respiratory chain results in a dramatic increase of reducing equivalents both in the mitochondria and cytoplasm. The general consequence of this is the increase of ketone body molar ratio (3-hydroxybutyrate/acetoacetate) and lactate/pyruvate molar ratio in plasma. The determination of these ratios is useful deciding whether enzymological studies of the respiratory chain are required. The observation of an abnormal oxidoreduction status in patients with Pearson marrow-pancreas syndrome led us to identify this disease as a mitochondrial cytopathy. Moreover, we were able to show that rearrangements of the mitochondrial genome are consistent features of this disease.     

Effects of a multidisciplinary family treatment drug court on child and family outcomes: results of a quasi-experimental study

Family treatment drug courts (FTDCs) are an increasingly common approach for serving families involved in child welfare due to parental substance abuse; however, the evidence base for FTDCs remains emergent. This quasi-experimental study replicates previous research on FTDCs by comparing parental substance abuse treatment and child welfare outcomes for 76 FTDC participants to outcomes for 76 parents in the same system who did not participate in the FTDC, using propensity score matching. Data were obtained from the Superior court, FTDC, child welfare, and public substance use treatment service administrative databases. The follow-up window for participants ranged from 1 to 3 years. Results showed FTDC parents had significantly more review and motion hearings, were significantly more likely to enter treatment, entered treatment faster, received more treatment, and were more likely to successfully complete treatment. FTDC children spent significantly less time placed out of home, ended child welfare system involvement sooner, were more likely to be permanently placed and discharged from child welfare, and were more likely to return to parental care. Results demonstrate that FTDCs promote positive treatment and child welfare outcomes without deepening participants' involvement in justice systems.     

Serum antibodies against gliadin and reticulin in a family study of coeliac disease

The familial occurence of coeliac disease is well known. In every day practice, however, diagnosis of coeliac disease is not frequently established in the relatives of patients. As it did not seem practicable to biopsy all relatives, several tests were investigated in selecting individuals for intestinal biopsy in a family study. 55 index patients out of 54 families with biopsy-proven coeliac disease and 165 of their first grade relatives underwent the study. Immunofluorescent gliadin and reticulin antibodies were determined, and additionally laboratory tests were done. These included haemoglobin, serum iron, serum protein and albumin, serum immunoglobulins and blood xylose. The immunofluorescent gliadin antibody assay using red cells coated with gliadin proved to be superior to the other methods. False negatives came to 8.7%, and false positives 10.9%, in healthy relatives. Gliadin antibodies could be found five times more frequently in healthy relatives than in normal controls. This finding indicates a genetic predisposition to the formation of gliadin antibodies in coeliac families.Ninety-one percent of index coeliac children had IgG-antigliadin in their sera while on a normal diet. During gluten-free diet, and in adult patients, results were less convincing. All relatives with antigliadin titres greater than 8 have been biopsied, and all with titres above 64 were shown to have coeliac disease. The prevalence of coeliac disease found in this study was 5.5%. In the active state of coeliac disease in children, gliadin antibody determination thus is a valuable diagnostic tool but in selecting relatives for biopsy there are limitations to the wide application of the test. Although reticulin antibodies are more specific for coeliac disease than gliadin antibodies, determination of antireticulin proved to be much less sensitive.Supported by Deutsche Forschungsgemeinschaft Gr 278/6 and Ste 305/1     

Aspirin in acute gastroenteritis: a clinical and microbiological study

Soluble aspirin given by mouth in divided dosage decreased intestinal fluid loss in infants and young children with acute gastroenteritis. The treated group had significantly less diarrhea, which ceased earlier and needed less intravenous therapy, than a randomly selected control group given an indistinguishable placebo. This effect of aspirin occurred with diarrhea caused by Salmonella, Aeromonas, Escherichia coli producing heat-labile toxin, and rotavirus, but not with diarrhea associated with strains of E. coli producing heat-stable toxin.