Abstract
DOI: 10.26650/experimed.2018.430582
Smith–Lemli–Opitz syndrome (SLOS) is a
cholesterol synthesis disorder, with an etiology of severe malnutrition, which
is often excluded from typical differential diagnostic strategies. However,
SLOS can be detected during a careful physical examination; thus, it was
selected to draw attention to the malnutrition etiology.It was selected to
exemplify how an inborn error in cholesterol metabolism can induce
malnutrition. A four month old girl was referred to our polyclinic with a
diagnosis of severe acute malnutrition since 4 months. She was the only child
from a second pregnancy; the first child of her non-consanguineous parents was
lost due to an abortion. Physical examination involving weight, height, and
head circumference were at third centimeter persentile and below; additionally,
dysmorphic facial appearance and syndactyly between the second and third finger
of the foot feet was noted. Neuromotor development was normal for her age.
Suspecting a phenotype suggesting a congenital problem, a lipid analysis was
performed that revealed hypolipidemia. SLOS was considered as a differential
diagnosis. Accordingly, the level of biomarker 7 dehydrocholesterol was
assessed controlled and was found to be 1772, which was considerably higher
than normal (normal < 10 mmol/L). Subsequently, molecular assay revealed
pTyr432Cys (c.1295A> G) htr pArg446Trp (c.1336C> T) heterozygous mutation.
Steroid hormone levels, bile acid synthesis, fat-soluble vitamin absorption,
and central nervous system development may be negatively affected because they
were evaluated in detail. No other pathology was detected except for a patent
foramen ovale. A replacement therapy comprising of bile acids (ursodeoxycholic
acid 15–25 mg/kg/day) and cholesterol (50–100 mg/kg/day) was initiated, along
with a cholesterol-rich diet. After 1 month, the patient weighed 5935 g, with a
height of 69 cm, head circumference of 38 cm, total cholesterol level of 83
mg/dL, High density lipoprotein (HDL) level of 30 mg/dL, and Low density
lipoprotein (LDL) level of 32 mg/dL. However, the patient’s nutrient intake was
not adequate, and percutaneous endoscopic gastrostomy was initiated, following
which the patient’s weight and cholesterol levels improved. To reach SLOS
diagnosis, it is necessary to conduct full physical examination, including
taking out the socks; looking at toe finger structure; evaluating head size,
palate, uvula, and external genitals; and observing signs of mental
retardation. In routine tests for assessing malnutrition, triglyceride and
cholesterol control are not performedassesed. The evaluation of the serum lipid
profile should not be overlooked in patients with dysmorphic malnutrition.
References
- Alberda, C., Graf, A., McCargar, L., 2006. Malnutrition: Etiology, consequences, and assessment of a patient at risk. Best Pract. Res. Clin. Gastroent. 20, 419–439.
- Mitsche, M.A., McDonald, J.G., Hobbs, H.H., Cohen, J.C., 2015. Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways. eLife. 4,1-21.
- Xu, L. ve Porter, N.A., 2015. Free radical oxidation of cholesterol and its precursors: Implications in cholesterol biosynthesis disorders. Free Radic Res. 49, 835–849.
- Boland, M.R. ve Tatonetti, N.P., 2016. Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review. Pharmacogenomics J. 16, 411–429.
- Slominski, A.T., Li, W., Kim T.K., Semak, I., Wang, J., Zjawiony, J.K., Tuckey,R. C., 2015. Novel activities of CYP11A1 and their potential physiological significance. J Steroid Biochem Mol Biol. 151, 25–37.
- Nowaczyk, M. J.M. ve Irons, M.B., 2012. Smith–Lemli–Opitz Syndrome: Phenotype, Natural History, and Epidemiology. Am. J. Med. Gen. 160C,250–262.
- Porter, F.D., 2008. Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management Eur. J. Hum. Gen. 16, 535–541.
Abstract
DOI: 10.26650/experimed.2018.430582
Ağır malnutrisyon etiolojisinde kolesterol
sentez bozukluklarından biri olan Smith Lemli Opitz (SLOS) klasik ayırıcı tanı
şemalarında yer almamaktadır. Dikkatli fizik muayene ile ipuçları yakalanabilen
bu hastalığa malnutrisyon etiolojisinde dikkat çekmek için bu olgu seçilmiştir.
Akrabalığı olmayan ailenin ilki abortus 2. gebeliğinden yaşayan tek çocuk olan
kız hasta kilo alamama şikayeti ile 4 aylık ağır akut malnutrisyon tanısı
ile polikliniğimize yönlendirilmişti.
Fizik muayenede tartı, boy, baş çevresi 3. persentil ve altında olup, ayak 2-3.
parmak arası sindaktilisi, dismorfik yüz görünümü mevcuttu. Nöromotor gelişimi
yaşına uygundu. Fenotipten şüphelenilerek istenen lipid analizinde hipolipidemi
olduğu görüldü. SLOS ayırıcı tanıda düşünülüp biyomarkerı 7 dehidrokolesterol
(7DHK) istendi. 7DHK düzeyi 1772 ( n<10 mmol/L) yüksek saptanıp; moleküler
tetkikle p.Tyr432cys (c.1295 A>G) htr p.Arg446Trp(c.1336C>T) heterozigot
mutasyonu tespit edildi. Hastanın steriod hormonları, safra asidi sentezi,
yağda eriyen vitamin emilimi, merkezi sinir sistemi gelişimi etkilenebileceği
için ayrıntılı değerlendirildi. Patent foramen ovale dışında patoloji saptanmadı.
Tedavide safra asidleri (ursodeoksikolik asid 15-25 mg/kg/gün), kolesterol (50-100 mg/kg/gün) yerine koyma tedavisi
başlandı. Diyet kolesterolden zengin olarak düzenlendi. 1 ay sonra Tartı: 5935
g, boy: 69 cm, baş çevresi: 38 cm, total kolesterol: 83mg/dL, HDL: 30mg/dL,
LDL: 32mg/dL, bulundu. Hastanın besin tüketiminin yeterli olmadığı öğrenildi.
Perkütan endoskopik gastrostomi enteral beslenmeye geçildikten sonra kilo ve
kolesterol düzeyleri düzeldi. Smith Lemli Opitz tanısı için tam fizik muayene
yapılarak, çorapları çıkarmak parmak yapısına bakmak, uvulayı kontrol edip
bifid uvula aramak gibi ayrıntıya dikkat etmek gerekir. Malnutrisyon rutin
tetkikleri arasında trigliserid, kolesterol kontrolü yoktur. Dismorfik
malnutrisyonlu hastalarda lipid profili kontrolü unutulmamalıdır.
References
- Alberda, C., Graf, A., McCargar, L., 2006. Malnutrition: Etiology, consequences, and assessment of a patient at risk. Best Pract. Res. Clin. Gastroent. 20, 419–439.
- Mitsche, M.A., McDonald, J.G., Hobbs, H.H., Cohen, J.C., 2015. Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways. eLife. 4,1-21.
- Xu, L. ve Porter, N.A., 2015. Free radical oxidation of cholesterol and its precursors: Implications in cholesterol biosynthesis disorders. Free Radic Res. 49, 835–849.
- Boland, M.R. ve Tatonetti, N.P., 2016. Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review. Pharmacogenomics J. 16, 411–429.
- Slominski, A.T., Li, W., Kim T.K., Semak, I., Wang, J., Zjawiony, J.K., Tuckey,R. C., 2015. Novel activities of CYP11A1 and their potential physiological significance. J Steroid Biochem Mol Biol. 151, 25–37.
- Nowaczyk, M. J.M. ve Irons, M.B., 2012. Smith–Lemli–Opitz Syndrome: Phenotype, Natural History, and Epidemiology. Am. J. Med. Gen. 160C,250–262.
- Porter, F.D., 2008. Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management Eur. J. Hum. Gen. 16, 535–541.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Makale |
| Authors | |
| Publication Date | April 30, 2018 |
| Published in Issue | Year 2018 Volume: 8 Issue: 1 |
