Loss of the SEDL gene product (Sedlin) causes X‐linked spondyloepiphyseal dysplasia tarda: Identification of a molecular defect in a Japanese family

A 23‐year‐old man was diagnosed as having X‐linked spondyloepiphyseal dysplasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterior hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5′ untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mutation was present in the proband and his unaffected mother (a heterozygote), but not in an unaffected sister and an unaffected uncle. The nature of the mutation predicted that the SEDL protein (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused SEDT. © 2001 Wiley‐Liss, Inc.     

Hereditary uroporphyrinogen-decarboxylase deficiency predisposing porphyria cutanea tarda (chronic hepatic porphyria) in females after oral contraceptive medication

Summary Porphyria cutanea tarda (PCT) was diagnosed in 27 women aged 23–48 years (mean, 35 years) who had been under oral-hormonal-contraceptive medication for 1–18 years, in 3 women under substitutional estrogen treatment in the menopause, and in 2 men aged 65 and 76 years after estrogen treatment of prostatic carcinoma. In all patients, total urinary porphyrin excretion was elevated, with an average uro-and heptacarboxyporphyrin predominance of 88%, thus proving PCT. On the patients, 84% showed a significant decrease of erythrocyte uroporphyrinogen-decarboxylase (UD; EC 4.1.1.37) activity to 50% of control levels suggesting a hereditary predisposition for the development of a chronic hepatic porphyria. Estrogens and alcohol are capable of reducing hepatic UD activity. Women with hereditary red cell UD deficiency may be regarded as predisposed to PCT when under estrogen intake, especially in combination with the potentiating influence of alcohol and chronic liver disease. Normal erythrocyte UD values in patients with additive alcohol consumption may implicate a stronger inhibitory effect for alcohol on UD, suggesting a merely toxic form of chronic hepatic porphyria.     

The effects of ethanol,estrogen, and hexachlorobenzene on the activities of hepatic δ-aminolevulinate synthetase, δ-aminolevulinate dehydratase,and uroporphyrinogen decarboxylase in male rats

To determine if clinically observed disorders in heme biosynthetic enzymes, known as sporadic porphyria cutanea tarda (PCT), could be reproduced in experimental animals, male Fischer rats were treated with ethanol, estrogen and hexachlorobenzene (HCB). A series of heme biosynthetic enzymes were assayed. In the rats given free access to 8% ethanol-drinking water for 15 weeks, -aminolevulinate (ALA) dehydratase was significantly reduced in erythrocytes. In the liver, ALA synthetase and uroporphyrinogen (UROgen) decarboxylase activities remained unchanged. In bone marrow cells, these activities did not change markedly. In the rats treated with estrogen (1 mg estrioltripropionate /rat/week, IM), no body weight gain was observed during the treatment for 15 weeks and urinary ALA excretion increased to 1.7 fold over normal level. In the liver, a significant increase was observed in the activity of ALA dehydratase, but other enzymes remained within the normal level. In bone marrow cells and erythrocytes, ALA dehydratase was also increased. ALA synthetase increased only in bone marrow cells to 2.1 times higher than the control level. In rats fed 0.3% HCB-diet for 8 weeks, urinary excretion of ALA, coproporphyrin and uroporphyrin increased to 2.4, 3.3 and 3.8 times higher than the controls, respectively. In the liver, an increase was observed in ALA synthetase, while a decrease was observed in ALA dehydratase and UROgen decarboxylase. In bone marrow cells and erythrocytes, ALA dehydratase was reduced and activities of other enzymes did not show any changes.These results indicate that alcohol, estrogen and HCB do not produce phenomena similar to those observed clinically in PCT.     

Porphyria cutanea tarda and Sjogren's syndrome

Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren''s syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren''s syndrome.     

A novel missense variant in TRAPPC2 causes X-linked spondyloepiphyseal dysplasia tarda: A case report

Rationale:X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is a rare hereditary cause in childhood short stature due to mutations in trafficking protein particle complex subunit 2 (TRAPPC2) gene located on chromosome Xp22. Several pathogenic variants in TRAPPC2 have been reported, but missense variants are rare.Patient concerns:A 13-year, 8-month-old Chinese Han boy presenting with short stature for the past 7 years.Diagnosis:X-linked SEDT was established by a combination of clinical and radiographic features, confirmed by targeted next-generation sequencing. Genetic testing of the TRAPPC2 gene revealed a novel missense variant with c.260A>C (p.H87P) hemizygote in exon5. The mother was found to be a heterozygous TRAPPC2 carrier, whereas the father was normal.Interventions:Patient was treated with recombinant human growth hormone daily. Patient''s height, glucose level, and possible progressive joint and back pain with osteoarthritis were under intensive observation regularly.Outcomes:The patient achieved 2.1 cm height gain over the first 3 months’ recombinant human growth hormone treatment without joint or back pain. However, the therapy was terminated because of increased glucose level on follow-up.Lessons:The short stature is a noteworthy problem for X-linked SEDT cases. We report a novel missense variant site in TRAPPC2 treated with growth hormone in the literature. We do not recommend the use of recombinant human growth hormone on patients with X-linked SEDT for the concern of glucose homeostasis.     

Radiographic diagnosis of the occult hip fracture: Experience in 16 patients

We have benefited from using a simple, time-saving radiographic procedure for more than 5 years which may establish a correct diagnosis in most patients with clinically suspected, but initially occult, hip fractures.     

大鲵的迟钝爱德华菌感染

目的对大鲵不明原因死亡进行病原学鉴定，并根据药物敏感实验结果选用抗生素治疗。方法从患病死亡大鲵足部溃烂病变部位及心脏取血采样，分别用液体培养基、普通琼脂平板、血平板进行增菌和画线培养分离，经法国Biomerirux VITEK 2全自动微生物分析系统检测。结果与结论引起感染是迟钝爱德华菌（E．tarda），该病原体对庆大霉素、头孢曲松钠和环丙沙星等抗菌药物敏感，用敏感的庆大霉素和头孢曲松钠处理，控制了感染的流行。