U dvouletého chlapce s nízkou hladinou estriolu v séru matky během těhotenství, anamnézou nepostupujícího porodu ukončeného císařským řezem pro hypoxii plodu se zkalenou plodovou vodou, kožními projevy ichtyózy, které se objevily ve druhémtýdnu života, a těžkou poruchou psychomotorického vývoje byla diagnostikována X-vázaná ichtyóza. Enzymatická vyšetření u chlapce, jeho matky, babičky, tety a matčina bratrance ukázala poruchu aktivity steroidsulfatázy (STS). Cytogenetické vyšetření metodou FISH u probanda i jeho příbuzných ukázalo mikrodeleci genu pro STS. Protože postižení CNS obvykle nepatří do klinického obrazu X-vázané ichtyózy, autoři se domnívají, že na vzniku psychomotorické retardace u chlapce se nejspíše podílela perinatální hypoxie při protrahovaném porodu v důsledku snížené hladiny estrogenů při deficitu placentární STS, která se podílí na syntéze estrogenů. Nemohou však vyloučit ani postnatální postižení CNS po prodělané hypernatremické dehydrataci a/nebo hypoxii při aspirační pneumonii v novorozeneckém věku. V literatuře již byl u chlapců s X-vázanou ichtyózou protrahovaný porod opakovaně popsán. Předpokládá se, že protrahovaný porod u chlapců s X-vázanou ichtyózou je způsoben nízkou hladinou estrogenů při nedostatečné aktivitě placentární STS. Ačkoliv se deficit aktivity STS vyskytuje pouze u 1 chlapce ze 2–6000, měl by být nález nízké hladiny estriolu u těhotné ženy varovným signálem pro ošetřující lékaře, aby v rámci diferenciálně diagnostické rozvahy pomýšleli i na možnost X-vázané ichtyózy.
X-linked ichthyosis was diagnosed in a 2-year old boy with lowmaternal estriol serum levels during gestation. The prolonged delivery was terminated by Caesarian section due to fetal hypoxia and turbid amniotic fluid. Apgar score was uneventful, but early postnatal adaptation was complicated by failure to thrive and hypotonia followed on by hypernatremic dehydration and aspiration pneumonia in the second week of life. At this time, cutaneous manifestations of ichthyosis was also observed and severe psychomotor retardation developed since early infancy. Enzymatic investigations in the proband, his mother and her relatives including grandmother, sister and her son revealed steroid sulfatase (STS) deficiency and the cytogenetic analyses using FISH method revealed the microdeletion of STS gene. The central nervous system impairment is usually not present in patients with X-linked ichthyosis. Although in our patient the role of hypernatremic dehydration and/or eventual hypoxia during aspiration pneumonia cannot be excluded as a cause of the postnatal CNS impairment, we suppose that also the perinatal hypoxia might be important in a boy with prolonged delivery resulting fromlowmaternal estrogens and placental STS deficiency. Because the STS deficiency affects approximately 1 in 2–6000 males, the low estriol level in pregnant woman should be an alerting marker for physicians to give a though to possibility of X-linked ichthyosis.
- MeSH
- Cytogenetic Analysis methods utilization MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Estriol blood deficiency secretion MeSH
- Financing, Organized MeSH
- Ichthyosis, X-Linked diagnosis drug therapy therapy MeSH
- Obstetric Labor Complications etiology surgery blood MeSH
- Pregnancy Complications surgery blood MeSH
- Humans MeSH
- Mutation genetics MeSH
- Child, Preschool MeSH
- Psychomotor Disorders diagnosis etiology MeSH
- Pregnancy blood metabolism MeSH
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities diagnosis genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Pregnancy blood metabolism MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Based on Internet search, we were contacted by a 50-year-old man suffering from severe abdominal pain. Acute hepatic porphyria was considered from positive Watson-Schwartz test. He, not being a health professional, searched for centres with ability to do molecular diagnosis and for information about therapeutic possibilities. He asked his physician for haem-arginate (Normosang, Orphan Europe, Paris) treatment, arranged sending his blood to our laboratory and mediated genetic counselling for him and his family. Molecular analyses of the PBGD gene revealed a novel mutation in exon 15, the 973insG. Subsequently, genetic analysis was performed in 18 members of the proband's extensive family. In 12 members of the family, the same mutation was found. The mutation, which consisted of one nucleotide insertion, resulted in addition of four different amino acids leading to a protein that is prematurely truncated by the stop codon. The effect of this mutation was investigated by expression of the wildtype and mutated PBGD in a prokaryotic expression system. The mutation resulted in instability of the protein and loss of enzymatic function. The increasing access to a number of disease- and symptom-oriented web pages presents a new and unusual venue for gaining knowledge and enabling self-diagnosis and self-help. It is, therefore, important that diseaseoriented Internet pages for public use should be designed with clarity and accurate current knowledge based background.
- MeSH
- Porphyria, Acute Intermittent diagnosis genetics blood MeSH
- Molecular Diagnostic Techniques methods utilization MeSH
- Adult MeSH
- Electrophoresis methods utilization MeSH
- Financing, Organized utilization MeSH
- Mutation genetics MeSH
- DNA Mutational Analysis methods utilization MeSH
- Men MeSH
- Polymerase Chain Reaction methods utilization MeSH
- Porphobilinogen isolation & purification blood MeSH
- Check Tag
- Adult MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Genetic Diseases, Inborn MeSH
- Infant MeSH
- Humans MeSH
- Menkes Kinky Hair Syndrome * diagnosis genetics MeSH
- Prognosis MeSH
- Psychomotor Disorders MeSH
- Metabolism, Inborn Errors MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
