GPD1 Deficiency - Underdiagnosed Cause of Liver Disease

J 2021

GPD1 Deficiency - Underdiagnosed Cause of Liver Disease

TESAŘOVÁ, Markéta, Viktor STRANECKÝ, Petra KONEČNÁ, Dagmar PROCHÁZKOVÁ, Helena HŮLKOVÁ et. al.

Základní údaje

Originální název

GPD1 Deficiency - Underdiagnosed Cause of Liver Disease

Název česky

Deficit GDP1 - poddiagnostikovaná příčina jaterního postižení

Autoři

TESAŘOVÁ, Markéta (203 Česká republika), Viktor STRANECKÝ (203 Česká republika), Petra KONEČNÁ (203 Česká republika, domácí), Dagmar PROCHÁZKOVÁ (203 Česká republika, domácí), Helena HŮLKOVÁ (203 Česká republika), Jiří ZEMAN (203 Česká republika), Tomáš HONZÍK (203 Česká republika) a Martin MAGNER (203 Česká republika, garant)

Vydání

The Indian Journal of Pediatrics, New Dehli, Springer, 2021, 0019-5456

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30209 Paediatrics

Stát vydavatele

Indie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.319

Kód RIV

RIV/00216224:14110/21:00120631

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1007/s12098-020-03385-x

UT WoS

000543602000006

Klíčová slova česky

GDP1 deficit

Klíčová slova anglicky

GDP1 deficiency

Štítky

14110317, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 1. 2021 10:40, Mgr. Tereza Miškechová

Anotace

ORIG CZ

V originále

Deficiency of cytosolic glycerol-3-phosphate dehydrogenase (GPD1, EC 1.1.1.8) manifests in infancy with hepatomegaly, moderate to severe hypertriglyceridemia and cholestasis resulting in steatosis and fibrosis but the course of the disease seems to be non-progressive and relatively be nign . Among 17 patients described so far, severe liver disease was found in one patient only. We report infantile hypertriglyceridemia/GPD1 deficiency (OMIM #614480) in nine Roma children and one boy of Palestinian Arab origin. The main symptoms included, early onset mod erate to severe hepatomegaly (9 of 10 patients), hepatopathy (AST 63,600–309,600 IU/ml, controls<58,200; ALT 35,500–151,200 IU/ml, controls<51,200; GGT 57,600- 1,416,000 IU/ml, controls<62,400) and hypertriglyceridemia (189–1062 mg/dl, controls 44–195). Coagulation tests and extensive serologic and metabolic analyses were normal except for mild repeated hypoglycemia (50.5–55.9 mg/dl, controls 70.2–100.9) in two infants. The children are now between 2 and 17 y old, and they are of low-normal growth. All our Roma patients were homozygous for a novel mutation c.895G>A (p.Gly299Arg), the boy of Palestinian Arab origin was homozygous for a novel mutation c.116G >A (p.Trp39*) in GPD1. The mutations were not found in the GnomAD database and were predicted to be pathogenic. The pathogenicity of the c.895G >A substitution was supported by the absence of homozygosity in patient’s healthy siblings and parents. Our results indicate a high frequency of the mutation in the Roma population, probably due to the founder effect. Although the clinical and laboratory features stabilized or improved in children with no signs of liver failure, liver biopsy performed in six patients revealed combined micro/ macrovesicular steatofibrosis and even signs of transition to cirrhosis in two boys. Such an early development of cirrhosis in some children opposes the current conception of GPD1 being a benign or transient disease. Therefore we suggest that the original name of the disease “transitory infantile hypertri- glyceridemia” be abandoned and replaced by “GPD1 deficiency”. As there are no specific biochemical markers for GPD1 deficiency except for elevated aminotransferases and triglycerides (typically without hypercholesterolemia), the underdiagnosis of GPD1 deficiency is very probable in children or adolescents with hepatomegaly and/or hepatopathy of unknown origin or non-alcoholic steatohepatitis (NASH).

Česky

Autoři prezentují 10 pacientů s tzv. tranzitorní infantilní hypertriglyceridémií, tj. deficitem glycerol-3-fosfát dehydrogenázy, GPD1. Onemocnění se manifestuje v dětství jako hepatomegálie, cholestáza, mírná až těžké hypertriglyceridémie s pozdějším možným nástupem jaterní fibrozy a cirhozy. Byla popsána nová patogenní sekvenční varianta c.895G>A (p.Gly299Arg), která je typická pro romské probandy.

Citovat

TESAŘOVÁ, Markéta, Viktor STRANECKÝ, Petra KONEČNÁ, Dagmar PROCHÁZKOVÁ, Helena HŮLKOVÁ, Jiří ZEMAN, Tomáš HONZÍK a Martin MAGNER. GPD1 Deficiency - Underdiagnosed Cause of Liver Disease. The Indian Journal of Pediatrics. New Dehli: Springer, 2021, roč. 88, č. 1, s. 80-81. ISSN 0019-5456. Dostupné z: https://dx.doi.org/10.1007/s12098-020-03385-x.

@article{1661297,
   author = {Tesařová, Markéta and Stranecký, Viktor and Konečná, Petra and Procházková, Dagmar and Hůlková, Helena and Zeman, Jiří and Honzík, Tomáš and Magner, Martin},
   article_location = {New Dehli},
   article_number = {1},
   doi = {http://dx.doi.org/10.1007/s12098-020-03385-x},
   keywords = {GDP1 deficiency},
   language = {eng},
   issn = {0019-5456},
   journal = {The Indian Journal of Pediatrics},
   title = {GPD1 Deficiency - Underdiagnosed Cause of Liver Disease},
   url = {https://link.springer.com/article/10.1007/s12098-020-03385-x},
   volume = {88},
   year = {2021}
}

TY  - JOUR
ID  - 1661297
AU  - Tesařová, Markéta - Stranecký, Viktor - Konečná, Petra - Procházková, Dagmar - Hůlková, Helena - Zeman, Jiří - Honzík, Tomáš - Magner, Martin
PY  - 2021
TI  - GPD1 Deficiency - Underdiagnosed Cause of Liver Disease
JF  - The Indian Journal of Pediatrics
VL  - 88
IS  - 1
SP  - 80-81
EP  - 80-81
PB  - Springer
SN  - 00195456
KW  - GDP1 deficiency
UR  - https://link.springer.com/article/10.1007/s12098-020-03385-x
L2  - https://link.springer.com/article/10.1007/s12098-020-03385-x
N2  - Deficiency of cytosolic glycerol-3-phosphate dehydrogenase (GPD1, EC 1.1.1.8) manifests in infancy with hepatomegaly, moderate to severe hypertriglyceridemia and cholestasis resulting in steatosis and fibrosis but the course of the disease seems to be non-progressive and relatively be nign . Among 17 patients described so far, severe liver disease was found in one patient only. We report infantile hypertriglyceridemia/GPD1 deficiency (OMIM #614480) in nine Roma children and one boy of Palestinian Arab origin. The main symptoms included, early onset mod erate to severe hepatomegaly (9 of 10 patients), hepatopathy (AST 63,600–309,600 IU/ml, controls<58,200; ALT 35,500–151,200 IU/ml, controls<51,200; GGT 57,600- 1,416,000 IU/ml, controls<62,400) and hypertriglyceridemia (189–1062 mg/dl, controls 44–195). Coagulation tests and extensive serologic and metabolic analyses were normal except for mild repeated hypoglycemia (50.5–55.9 mg/dl, controls 70.2–100.9) in two infants. The children are now between 2 and 17 y old, and they are of low-normal growth. All our Roma patients were homozygous for a novel mutation c.895G>A (p.Gly299Arg), the boy of Palestinian Arab origin was homozygous for a novel mutation c.116G >A (p.Trp39*) in GPD1. The mutations were not found in the GnomAD database and were predicted to be pathogenic. The pathogenicity of the c.895G >A substitution was supported by the absence of homozygosity in patient’s healthy siblings and parents. Our results indicate a high frequency of the mutation in the Roma population, probably due to the founder effect. Although the clinical and laboratory features stabilized or improved in children with no signs of liver failure, liver biopsy performed in six patients revealed combined micro/ macrovesicular steatofibrosis and even signs of transition to cirrhosis in two boys. Such an early development of cirrhosis in some children opposes the current conception of GPD1 being a benign or transient disease. Therefore we suggest that the original name of the disease “transitory infantile hypertri- glyceridemia” be abandoned and replaced by “GPD1 deficiency”. As there are no specific biochemical markers for GPD1 deficiency except for elevated aminotransferases and triglycerides (typically without hypercholesterolemia), the underdiagnosis of GPD1 deficiency is very probable in children or adolescents with hepatomegaly and/or hepatopathy of unknown origin or non-alcoholic steatohepatitis (NASH).
ER  -

TESAŘOVÁ, Markéta, Viktor STRANECKÝ, Petra KONEČNÁ, Dagmar PROCHÁZKOVÁ, Helena HŮLKOVÁ, Jiří ZEMAN, Tomáš HONZÍK a Martin MAGNER. GPD1 Deficiency - Underdiagnosed Cause of Liver Disease. \textit{The Indian Journal of Pediatrics}. New Dehli: Springer, 2021, roč.~88, č.~1, s.~80-81. ISSN~0019-5456. Dostupné z: https://dx.doi.org/10.1007/s12098-020-03385-x.

Podrobný výpis o publikaci