Inherited metabolic diseases

French national reference center for inherited metabolic diseases in children and adults (MAMEA)

The MAMEA rare diseases reference center takes care of children and adults with inherited metabolic diseases. For several years, it has been developing the most recent drug and dietetic treatments for diseases caused by intoxication by proteins and sugars, energy diseases, and enzyme replacement therapies, substrate reduction therapies for lysosomal diseases, various therapies for other metabolic diseases.

The Necker site works in close collaboration with the competence centers, in particular Rouen and Caen, other reference centers and patient associations throughout the country, the G2M healthcare network and European centers (métabERN).

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Pascale de Lonlay MaMea

Coordinator of the G2M healthcare network
Pr Pascale de Lonlay

Contact us

Secretariat of professor de Lonlay
Phone. 01 44 49 48 52
> Send an email
Secretariat of professor Schiff and doctor Pichard
Phone. 01 44 49 55 21
> Send an email
Secretariat of doctor Brassier and doctor Bouchereau
Phone. 01 44 49 47 31
> Send an email
Secretariat of doctor Arnoux
Phone. 01 44 49 40 23
> Send an email

Secretariat of doctor Servais
Phone. 01 44 49 54 13
> Send an email
Secretariat of doctor Dao
 01 44 49 54 58
> Send an email

In case of emergency

Inherited metabolic diseases (IMD) are the consequence of the genetic deficit of an enzyme or a transporter involved in numerous metabolic pathways.

They are classified into 3 groups according to a common pathophysiology:

  • Diseases by poisoning
  • Diseases by energy deficit
  • Diseases of complex molecules

IMDs are individually very rare (frequency of 1/5,000 to 1/500,000) but nevertheless remain very numerous since it is admitted that of the 4,000 to 6,000 potentially existing diseases, only around 500 are currently identified with new descriptions of diseases that are sometimes difficult to classify.

The first two groups are also often referred to as disorders of intermediary metabolism, involving the metabolism of proteins, sugars, lipids and it is these diseases that are at risk for acute decompensation.

These « metabolic distresses » can present themselves at any age, in different forms.

It is very important to mention them because most are treatable, the treatment saves life in the short term and changes the prognosis, especially neurological, in the medium and longer term.

Beyond the diagnostic and therapeutic approach which are often mixed and complex in view of the rarity of pathologies, it is essential to think about it and know how to implement the first simple measures before entrusting the patient to experienced teams, within reference and competence centers.

IMDs represent a challenge not only for the patient through care, particularly in the event of a metabolic emergency, but also for the family through genetic counseling and prenatal diagnosis on an individual scale.

At the collective level, the question of extending neonatal screening for certain IMDs arises, in particular thanks to current technical possibilities, better knowledge of the natural history of diseases and the development of specific therapies, this consideration being guided by ethics.

Diseases by poisoning

This group includes diseases of the intermediary metabolism which lead to acute or progressive intoxication by the accumulation of toxic compounds upstream of the enzymatic block.

This group includes aminoacidopathies (phenylketonuria, leukinosis, homocystinuria, tyrosinemia, etc.), organic acidurias (mathylmalonic, propionic, isovaleric aciduria, etc.), urea cycle deficits and related (OTC deficiency, lysinuric protein intolerance, etc.), sugar intolerances (galactosemia, hereditary fructose intolerance, etc.).

All of these conditions, with a few exceptions, share some common characteristics.

They do not interfere with embryo-foetal development and occur after a free interval after birth with clinical signs of acute (vomiting, lethargy, coma, multivisceral failure …) or chronic (anorexia, growth retardation, psychomotor retardation, cardiomyopathy …) intoxication.

They are likely to decompensate in « metabolic crises », recurrently during catabolic events (fever, intercurrent infection, fasting…) or when ingesting « toxic » foods.

Their diagnosis is based on blood and urine amino acid chromatography, urine organic chromatography and acylcarnitine profile. Most of these diseases can be treated by the purification of toxic compounds in emergency situations (hemodialysis, purifying drugs, etc.) and by special restrictive diets the rest of the time, for life.

Diseases by energy deficit

This group includes inherited metabolic diseases with symptoms linked, at least in part, to the failure to produce, use or store energy, involving the liver, striated muscle (peripheral and cardiac), brain, retina … high energy consumers.

It can be schematically divided into 2, distinguishing the defect of mitochondrial and cytoplasmic energy metabolism.

Mitochondrial energy deficits are the most severe and generally untreatable.

They include congenital lactic acidosis (mitochondrial pyruvate transporter deficiency, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency and Krebs cycle deficits), respiratory chain deficits (involving the 5 complexes of the respiratory chain but also mitochondrial transporters of energy molecules and the synthesis of Q10 coenzyme ),  fatty acid oxidation deficits and metabolism of ketone bodies.

Cytoplasmic energy deficits are generally less severe.

They include deficits in the metabolism of glycolysis (pentose pathway, etc.) and of glycogen (gluconeogenesis and glycogenolysis with hepatic and muscular glycogenoses), hyperinsulinisms, disorders of creatine metabolism.

Common warning signs are hypoglycemia, hepatomegaly, lactic acidosis, myo (cardio) pathy, growth retardation, hypotonia or various neurological symptoms, sudden death in childhood.

Certain mitochondrial deficits and deficits on the pentose pathway can interfere with embryo-fetal development and lead to dysmorphia, dysplasias and malformations.

Diagnosis is difficult and is based on functional explorations (fasting tests, etc.), enzymatic assays requiring cell cultures (skin, muscle biopsies, etc.) and on molecular analyzes.

Diseases of complex molecules

This group concerns intracellular organelles (lysosome, peroxisome, etc.) and groups together diseases that disrupt the synthesis or the catabolism of complex molecules within them: lysosomal and peroxisomal diseases, deficits in protein glycosylation (CDG syndromes) , deficits in the endogenous synthesis of cholesterol and bile acids as well as other deficits involving the trafficking of complex molecules.

Symptoms are permanent, progressive and independent of intercurrent events or diet since they concern structural proteins and not those involved in the pathways of intermediary metabolism.

These diseases are polymorphic, multiorgan, often with neurological expression, which can lead to damage as early as fetal life (foeto-placental hydrops, brain malformations, polymalformative syndromes, etc.);

The diagnosis is based on specific enzymatic assays which may be based on urine screening tests and the highlight of mutations in molecular biology.

Most of these diseases are not treatable, but there is currently enzyme replacement therapy for some of them and a large area of research devoted to the development of new therapies.

Energy metabolism

Mitochondrial diseases

  • Mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies
  • Coenzyme Q10 deficiency
  • Mitochondrial oxidative phosphorylation disorder due to mitochondrial DNA anomalies
  • Kearns-Sayre syndrome
  • Pearson Syndrome
  • Leber’s hereditary optic neuropathy
  • NARP syndrome
  • Maternal-transmitted diabetes-deafness
  • Isolated anomaly of an oxidative phosphorylation complex
  • « Uncharacterized » mitochondrial oxidative phosphorylation disorder

Lipoic acid biosynthesis defect

Creatine deficiency

  • Guanidinoacetate methyltransferase deficiency
  • L-arginine deficiency: glycine amidinotransferase
  • X-linked creatine transporter deficiency

Disorder of fatty acid oxidation and ketone body metabolism

  • Ketolysis disorder
  • Beta-ketothiolase deficiency
  • Succinyl-CoA deficiency: 3-ketoacid CoA transferase
  • Disorder of fatty acid oxidation and ketogenesis
  • Mitochondrial trifunctional protein deficiency
  • 3-hydroxy-3-methylglutaryl-CoA-Lyase deficiency
  • 3-hydroxy-3-methylglutaryl-CoA synthetase deficiency
  • Acyl-CoA dehydrogenase deficiency of medium chain fatty acids
  • Multiple acyl-CoA dehydrogenase deficiency
  • Short-chain fatty acid acyl-CoA dehydrogenase deficiency
  • Very long chain fatty acid acyl-CoA dehydrogenase deficiency
  • 3-hydroxyacyl-CoA dehydrogenase deficiency in long chain fatty acids
  • Short chain fatty acid 3-hydroxylacyl-CoA dehydrogenase deficiency
  • Carnitine palmitoyltransferase II deficiency
  • Carnitine palmitoyltransferase 1A deficiency
  • Primary systemic carnitine deficiency
  • Carnitine-acylcarnitine translocase deficiency
  • Malonic aciduria
  • Acyl-CoA dehydrogenase deficiency 9
  • Monocarboxylate transporter 1 deficiency Abnormal pyruvate metabolism
  • Pyruvate dehydrogenase deficiency
  • Red blood cell pyruvate kinase deficiency
  • Krebs cycle anomaly
  • Oxoglutaric aciduria

Amino acid metabolism

Amino acid absorption and transport disorder

  • Cystinuria
  • Dicarboxylic hyperaminoaciduria
  • Lysinuric protein intolerance
  • Hyperdibasic aminoaciduria type 1
  • Hypotonia-cystinuria syndrome
  • Hartnup disease
  • Iminoglycinuria

Urea cycle metabolism and ammonia detoxification disorder

  • Ornithine transcarbamylase deficiency
  • Argininemia
  • Argininosuccinic aciduria
  • Carbamoyl-phosphate synthetase 1 deficiency
  • Citrullinaemia type I
  • Citrullinaemia type II
  • Neonatal intrahepatic cholestasis due to citrine deficiency
  • Hyperornithinaemia-hyperammonemia-homocitrullinuria syndrome
  • N-acetylglutamate synthase deficiency
  • Hyperinsulinism syndrome and hyperammonemia
  • VA carbonic anhydrase deficiency

Metabolism disorders of the cycle of methionine, sulfur amino acids and cobalamin

  • Classic homocystinuria due to cystathionine beta-synthase deficiency / Orphanet link
  • Sulphite oxidase deficiency
  • Homocystinuria without methylmalonic aciduria
  • Homocystinuria due to methylene tetrahydrofolate reductase deficiency+ MTHF
  • Methylcobalamin deficiency type cblE
  • Methylcobalamin deficiency type cblG
  • Methylcobalamin deficiency type cblDv1
  • Hypermethioninaemia due to adenosine kinase deficiency
  • Hypermethioninaemia due to glycine N-methyltransferase deficiency
  • Methylmalonic acidemia with homocystinuria type cblC / Orphanet link
  • Methylmalonic acidemia with homocystinuria type cblD / Orphanet link
  • Methylmalonic acidemia with homocystinuria type cblF / Orphanet link
  • Methylmalonic acidemia with homocystinuria type cblJ / Orphanet link
  • Methylmalonic acidemia with homocystinuria type cblX / Orphanet link
  • Methylmalonic acidemia sensitive to vitamin B12 type cblA
  • Methylmalonic acidemia sensitive to vitamin B12 type cblB
  • Methylmalonic acidemia sensitive to vitamin B12 type cblDv2
  • Formiminoglutamic aciduria
  • Neurodegenerative syndrome due to cerebral folate transport deficit
  • Biotin-Thiamine-Responsive Basal Ganglia Disease
  • Encephalopathy due to thiamine pyrophosphokinase deficiency

Histidine metabolism disorder

Proline metabolism disorder

Ornithine metabolism disorder / Orphanet link

  • Gyrate atrophy of choroid and retina

Peptide metabolism disorder

  • Carnosinaemia
  • Prolidase deficiency
  • Homocarnosinosis

Phenylalanine metabolism disorder / Orphanet link

  • Classical phenylketonuria
  • Permanent moderate hyperphenylalaninaemia
  • Atypical phenylketonuria
  • Embryo-fetopathy associated with maternal PKU

Tyrosine metabolism disorder

  • Alcaptonuria
  • Hawkinsinuria
  • Tyrosinemia type 1
  • Tyrosinemia type 2
  • Tyronsinemia type 3

Serine or glycine metabolism disorder

  • Sacrosinemia
  • Hyperglycinemia without ketosis
  • Neurometabolic disease due to serine deficiency
  • 3-phosphoglycerate dehydrogenase deficiency
  • 3-phosphoglycerate dehydrogenase deficiency, infantile / juvenile form

Gamma-glutamyl cycle disorder

  • Glutathione synthetase deficiency
  • 5-oxopolinase deficiency
  • Gamma-glutamyl transpeptidase deficiency
  • Gamma-glutamylcysteine synthetase deficiency

Branched-chain amino acid metabolism disorder

  • Leukinosis / Orphanet link
  • Methylmalonate semialdehyde dehydrogenase deficiency
  • Branched-chain ketoacid kinase dehydrogenase deficiency

Tryptophan metabolism disorder

  • Hydroxykynureninuria

Lysine and hydroxylysine metabolism disorder

  • Hyperlysinemia
  • Sucropinuria
  • 2-Aminoadipic 2-oxoadipic aciduria
  • Hydroxylysinuria

Glutamine metabolism disorder

Organic aciduria

  • L-2-hydroxyglutaric aciduria
  • D-2-hydroxyglutaric aciduria
  • D, L-2-hydroxyglutaric aciduria
  • Glutaryl-CoA dehydrogenase deficiency
  • Canavan disease
  • Aminoacylase 1 deficiency
  • HSD10 disease
  • Isovaleric acidemia
  • Biotinidase deficiency / Orphanet link
  • Holocarboxylase synthetase deficiency
  • Beta-ketothiolase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-hydroxy-3-methylglutaric aciduria
  • 3-methylcrotonyl-CoA carboxylase deficiency
  • Propionic acidemia / Orphanet link
  • 2-methylbutyryl-CoA dehydrogenase deficiency
  • Isobutyryl-CoA dehydrogenase deficiency
  • 3-hydroxyisobutyryl-CoA hydrolase deficiency
  • Combined malonic and methylmalonic acidemia
  • 3-methylglutaconic aciduria
  • Barth syndrome
  • 3-methylglutaconic aciduria type 1
  • 3-methylglutaconic aciduria type 3
  • 3-methylglutaconic aciduria type 4
  • MEGDEL syndrome
  • 3-methylglutaconic aciduria type 7

Methylmalonic acidemia without homocystinuria / Orphanet link

  • Vitamin B12 unresponsive methylmalonic acidemia
  • Vitamin B12 type mut- unresponsive isolated methylmalonic acidemia
  • Vitamin B12 type mut0 unresponsive methylmalonic acidemia
  • Vitamin B12 responsive methylmalonic acidemia
  • Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency
  • Gamma-aminobutyric acid transaminase deficiency

Carbohydrate metabolism

  • Carbohydrate metabolism disorder
  • Fructose-1,6-diphosphatase deficiency
  • Phosphoenolpyruvate carboxykinase deficiency
  • Pyruvate carboxylase deficiency
  • Isolated glycerol kinase deficiency
  • Glycogenosis due to a depleting enzyme deficiency (type III glycogenosis)
  • Glycogenosis due to branching enzyme deficiency
  • Glycogenosis due to muscle glycogen phosphorylase deficiency
  • Glycogenosis due to hepatic phosphorylase deficiency
  • Glycogenosis due to muscle phosphofructokinase deficiency
  • Glycogenosis due to glucose-6-phosphatase deficiency (type I glycogenosis) / Orphanet link
  • Glycogenosis due to glucose-6-phosphatase type a deficiency
  • Glycogenosis due to glucose-6-phosphatase type b deficiency
  • Glycogenosis due to muscle aldolase A deficiency
  • Glycogenosis due to phosphoglycerate kinase 1 deficiency
  • Glycogenosis due to GLUT2 deficiency
  • Glycogenosis due to lactate dehydrogenase deficiency
  • Glycogenosis due to phosphoglycerate mutase deficiency
  • Glycogenosis due to muscle beta-enolase deficiency
  • Glycogenosis due to glycogenin deficiency
  • Glycogenosis due to hepatic glycogen synthase deficiency (type 0 glycogenosis)
  • Glycogenosis due to cardiac and muscle glycogen synthase deficiency
  • Triose-phosphate isomerase deficiency
  • Phosphoglucose isomerase deficiency
  • Hyperinsulinism due to glucokinase deficiency
  • Hereditary fructose intolerance
  • Galactokinase deficiency
  • Galactose epimerase deficiency
  • Classical galactosemia
  • D-glyceric aciduria
  • Primary hyperoxaluria
  • Congenital sucrase-isomaltase deficiency
  • Congenital lactase deficiency
  • Glucose-galactose malabsorption
  • GLUT1 deficiency
  • Transaldolase deficiency

Lysosomal metabolism

Neuronal ceroid lipofuscinosis

  • Adult neuronal ceroid lipofuscinosis
  • Infantile neuronal ceroid lipofuscinosis
  • Juvenile neuronal ceroid lipofuscinosis
  • Congenital neuronal ceroid lipofuscinosis
  • Late infantile neuronal ceroid lipofuscinosis
  • Acid phosphatase deficiency

Disorder of lysosomal amino acid transport

  • Cystinosis
  • Free sialic acid overload disease


  • Mucopolysaccharidosis type 6
  • Mucopolysaccharidosis type 7
  • Mucopolysaccharidosis type 2
  • Mucopolysaccharidosis type 1 / Orphanet link
  • Mucopolysaccharidosis type 3
  • 3A
  • 3B
  • 3C
  • 3D
  • Mucopolysaccharidosis type 4
  • 4A
  • 4B
  • Hyaluronidase deficiency


  • Multiple sulfatase deficiency
  • Farber’s disease
  • Krabbe disease
  • Fabry disease / Orphanet link
  • Metachromatic leukodystrophy
  • Gaucher disease / Orphanet link
  • Niemann-Pick disease type A
  • Niemann-Pick disease type B
  • Niemann-Pick disease type C  / Orphanet link
  • Lysosomal acid lipase deficiency
  • Niemann-Pick disease type E
  • Prosaposin deficiency
  • Gangliosidosis at GM1
  • Gangliosidosis at GM2
  • Mucolipidosis type II
  • Mucolipidosis type III
  • Alpha-mannosidosis
  • Aspartylglucosaminuria
  • Beta-mannosidosis
  • Fucosidosis
  • Galactosialidosis
  • Alpha-N-acetylgalactosaminidase deficiency
  • Sialidosis type 1
  • Sialidosis type 2
  • Sialuria
  • Wolman disease
  • Cholesterol ester storage disease

Glycogen storage diseases

  • Glycogenosis due to acid maltase deficiency
  • Glycogenosis due to LAMP-2 deficiency

Peroxysomal metabolism

  • Neonatal adrenoleukodystrophy
  • Infantile Refsum Disease
  • Refsum disease / Orphanet link
  • Acatalasemia
  • Glutaric acidemia type 3
  • Type 4 congenital bile acid synthesis deficiency
  • Acyl-CoA oxidase deficiency
  • X-linked adrenoleukodystrophy / Orphanet link
  • Bifunctional enzyme deficiency
  • Primary hyperoxaluria type 1
  • Rhizomelic punctate chondrodysplasia

Sterols and lipoproteins metabolism

Bile acid synthesis defect with cholestasis and malabsorption

  • Cerebrotendinous xanthomatosis / Orphanet link
  • Congenital bile acid synthesis defect type 4
  • Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency
  • Lathosterolosis
  • Smith-Lemli-Opitz Syndrome / Orphanet Link
  • Dessterolosis
  • Mevalonic aciduria / Orphanet link

Rare dyslipidemia

  • Rare hyperlipidemia
  • Combined hyperlipidemia
  • Hyperlipoproteinemia type 3
  • Major hypertriglyceridemia
  • Hyperalphalipoproteinemia
  • LCAT deficiency
  • Apolipoprotein A-I deficiency
  • Tangier disease


  • Abetalipoproteinemia
  • Chylomicron retention disease
  • Sitosterolemia

Other lipidosis

  • Sjögren-Larsson syndrome
  • Dorfman-Chanarin disease

Proteins glycosylation

  • N-glycosylation disorder (CDG Ia – CDG X) / N-glycosylation disorder on Orphanet
  • O-glycosylation disorder
  • O-xylosylglycan synthesis disorder
  • Multiple exostosis disease
  • Musculo-contractural type Ehlers-Danlos syndrome
  • Progeroid-type Ehlers-Danlos syndrome
  • Multiple disorders of glycosylation
  • Golgi oligomeric complex deficiency

Purines and pyrimidines metabolism

Hypoxanthine-guanine phosphoryl transferase deficiency

Pyrimidine metabolism disorder

  • Hereditary orotic aciduria
  • Dihydropyrimidine dehydrogenase deficiency
  • Dihydropyrimidinuria
  • Beta-ureidopropionase deficiency


Neurotransmitter abnormality

  • Monoamine oxidase A deficiency
  • Dihydropteridine reductase deficiency / Dihydropteridine reductase deficiency on Orphanet
  • 6-pyruvoyl-tetrahydropterin synthase deficiency
  • GTP cyclohydrolase I deficiency
  • Dopamine beta hydroxylase deficiency
  • Aromatic amino acid decarboxylase deficiency
  • Tyrosine hydroxylase deficiency
  • Dopamine transporter deficiency
  • 4-hydroxybutyric aciduria
  • Gamma-aminobutyric acid transaminase deficiency
  • B6 and B9-dependent epilepsy due to antiquitin deficiency
  • Pyridoxal phosphate-responsive seizures
  • Adenylosuccinate lyase deficiency
  • Adenosine phosphoribosyltransferase deficiency


Pascale de Lonlay MaMea

Head of the reference center
Pr Pascale de Lonlay

Manuel Schiff MaMea

Pr Manuel Schiff

Jean Baptiste Arnoux MaMea

Dr Jean-Baptiste Arnoux

Anaïs Brassier MaMea

Dr Anaïs Brassier

Juliette Bouchereau MaMea

Dr Juliette Bouchereau

Samia Pichard MaMea

Dr Samia Pichard

Claire Marine Berat MaMea

Dr Claire Marine Berat

Lucille Altenburger MaMea

Dr Lucile Altenburger

Adult physicians

Aude Servais Service Néphrologie Hôpital Necker à Paris.Avril 2016

Dr Aude Servais

photo-identite-femme magec2

Dr Myriam Dao


Jean Francois Benoist MaMea

Pr Jean François Benoist
PharmD, PhD

Chris Ottolenghi MaMea

Pr Chris Ottolenghi

Pr Robert Barouki

photo-identite-femme magec2

Dr Odile Rigal

Clément Pontoizeau MaMea

Dr Clément Pontoizeau

Apolline Imbard Mamea

Dr Apolline Imbard
PharmD, PhD

Allel Chabli MaMea

Dr Allel Chabli

Catherine Caillaud MaMea

Dr Catherine Caillaud

Sylvia Sanquer MaMea

Dr Sylvia Sanquer

Edouard le Guillou Mamea

Dr Edouard Le Guillou


Murielle Assoun MaMea

Murielle Assoun

Claire Belloche Mamea

Claire Belloche

Sandrine Dubois Mamea

Sandrine Dubois

Florence Serceau Mamea

Florence Serceau

Pierre Buret Mamea

Pierre Buret

photo-identite-femme magec2

Soraya Shafieivand

Sabine Dewulf Mamea

Sabine Dewulf

Bénédicte Samba MaMea

Bénédicte Samba


Valerie Barbier Mamea

Valérie Barbier

Clarisse Duchon Mamea

Clarisse Duchon

Occupational therapists

Virginie Germa MaMea

Virginie Germa

Elodie Deladrière MaMea

Élodie Deladrière

Psychomotor therapist

Manon Tessier MaMea

Manon Tessier

Social worker

Virginie Leboeuf MaMea

Virginie Leboeuf

Young children educator

photo-identite-femme magec2

Manuella Bayart

Physiotherapist masseuse

photo-identite-femme magec2

Marion Maquet


Delphine Mondain MaMea

Delphine Mondain

photo-identite-femme magec2

Malika Boucha

photo-identite-femme magec2

Nathalie Madouri

Sophie Bustos MaMea

Sophie Bustos

Yann Kobylko-Baybaud

photo-identite-femme magec2

Corinne Rochette

photo-identite-femme magec2

Nathalie Mandane

photo-identite-femme magec2

Isabelle Madelaine

  • Program title : « My health step by step » therapeutic education program
    Contact : Dr Manuel SCHIFF (Send an email)
    Location : MaMEA reference center for inherited metabolic diseases, Necker-Enfants malades hospital, Paris
    Additional information : Children from 5 years old and adults
  • Program title: Therapeutic education program for inherited metabolic diseases: Urea cycle disorders, organic aciduria, leukemia and glutaric aciduria type I
    Contact : Dr Pascale de LONLAY (Send an email)
    Location: MaMEA reference center for inherited metabolic diseases, Necker-Enfants malades hospital, Paris
    Additional information : Children from 0 to 18 years old and their parents
  • Program title: Therapeutic education program for inherited metabolic diseases: PDH deficiency, Glut-1 deficiency and mitochondrial cytopathy
    Contact : Dr Pascale de LONLAY (Send an email)
    Location: MaMEA reference center for inherited metabolic diseases, Necker-Enfants malades hospital , Paris
    Additional information : Children up to 18 years old and their parents
  • Program title : Therapeutic education program for inherited metabolic diseases: Fatty acid oxidation disorders
    Contact : Dr Pascale de LONLAY (Send an email)
    Location : MaMEA reference center for inherited metabolic diseases, Necker-Enfants malades hospital, Paris
    Additional information : Children up to 18 years old and their parents
  • Program title : Therapeutic education program for inherited metabolic diseases : Galactosemia and fructosemia
    Contact : Dr Pascale de LONLAY (Send a email)
    Location : MaMEA reference center for inherited metabolic diseases, Necker Enfants-malades hospital, Paris
    Additional information : Children from 0 to 18 years old and their parents
  • Program title : Therapeutic education program for inherited metabolic diseases: Glycogen storage disease and gluconeogenesis disorders
    Contact : Dr Pascale de LONLAY (Send a email)
    Location : MaMEA reference center for inherited metabolic diseases, Necker-Enfants malades hospital, Paris
    Additional information : Children up to 18 years old and their parents
  • Program title: Therapeutic education program for inherited metabolic diseases with dietary therapy : Hyperinsulinism
    Contact : Dr Pascale de LONLAY (Send an email)
    Location : MaMEA reference center for inherited metabolic diseases, Necker Enfants-malades hospital, Paris
    Additional information : Children up to 18 years old and their parents
  • Program title : Therapeutic education program for inherited metabolic diseases: Phenylketonuria, tyrosinemia, homocystinuria
    Contact : Dr Pascale de LONLAY (Send an email)
    Location : MaMEA reference center for inherited metabolic diseases, Necker Enfants-malades hospital, Paris
    Additional information : Children from 0 to 18 years old and their parents

Study of rhabdomyolysis and metabolic decompensations linked to fever and fasting. Link to inflammation. Immunometabolism.

FP7-Health-2012-Innovation-1: collaborative study (Liverpool, Slovakia, France) on clinical development of Nitisinone for Alcaptonuria


Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.
Claire-Marine Bérat, Sebastian Montealegre, Arnaud Wiedemann, Malou Le Corronc Nuzum, Amélie Blondel, Hugo Debruge, Aline Cano, Brigitte Chabrol et al.
J Inherit Metab Dis, 2021 Mar, PMID: 32929747 DOI: 10.1002/jimd.12314

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and progressive retinopathy: one case report followed by ERGs, VEPs, EOG over a 17-year period.
Florence Rigaudière, Eliane Delouvrier, Jean-François Le Gargasson, Paolo Milani, Hélène Ogier de Baulny, Manuel Schiff
Doc Ophthalmol, 2021 Jun, PMID: 33392894 DOI: 10.1007/s10633-020-09802-y

Real-world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid-free formulas in France and Germany: A retrospective observational study.
Pascale de Lonlay, Roland Posset, Ulrike Mütze, Karine Mention, Delphine Lamireau, Manuel Schiff, Aude Servais, Jean Baptiste Arnoux, Anaïs Brassier, Myriam Dao et al.
JIMD Rep, 2021 Mar 6, PMID: 33977036 PMCID: PMC8100389 DOI: 10.1002/jmd2.12207

Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.
Francis Rossignol, Marvid S Duarte Moreno, Jean-François Benoist, Manfred Boehm, Emmanuelle Bourrat, Aline Cano, Brigitte Chabrol, Claudine Cosson, José Luís Dapena Díaz et al.
Genet Med, 2021 Sep, PMID: 34040193 PMCID: PMC8463480 DOI: 10.1038/s41436-021-01200-2

Compromised mitochondrial quality control triggers lipin1-related rhabdomyolysis.
Yamina Hamel, François-Xavier Mauvais, Marine Madrange, Perrine Renard, Corinne Lebreton, Ivan Nemazanyy, Olivier Pellé, Nicolas Goudin, Xiaoyun Tang, Mathieu P Rodero, Caroline Tuchmann-Durand, Patrick Nusbaum, David N Brindley, Peter van Endert, Pascale de Lonlay
Cell Rep Med, 2021 Aug 17, PMID: 34467247 PMCID: PMC8385327 DOI: 10.1016/j.xcrm.2021.100370

Liver and brain differential expression of one-carbon metabolism genes during ontogenesis.
Apolline Imbard, Leslie Schwendimann, Sophie Lebon, Pierre Gressens, Henk J Blom, Jean-François Benoist
Sci Rep, 2021 Oct 26, PMID: 34702858 PMCID: PMC8548596 DOI: 10.1038/s41598-021-00311-9

Sebelipase alfa enzyme replacement therapy in Wolman disease: a nationwide cohort with up to ten years of follow-up.
Tanguy Demaret, Florence Lacaille, Camille Wicker, Jean-Baptiste Arnoux, Juliette Bouchereau, Claire Belloche, Cyril Gitiaux, David Grevent, Christine Broissand, Dalila Adjaoud, Marie-Thérèse Abi Warde, Dominique Plantaz, Soumeya Bekri, Pascale de Lonlay, Anaïs Brassier
Orphanet J Rare Dis, 2021 Dec 14, PMID: 34906190 PMCID: PMC8670257 DOI: 10.1186/s13023-021-02134-3

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.
Macarena Cabrera-Serrano, Laure Caccavelli, Marco Savarese, Anna Vihola, Manu Jokela, Mridul Johari, Thierry Capiod, Marine Madrange, Enrico Bugiardini, Stefen Brady et al.
Brain, 2021 Dec 27, PMID: 34957489 DOI: 10.1093/brain/awab484

A Review of Multiple Mitochondrial Dysfunction Syndromes, Syndromes Associated with Defective Fe-S Protein Maturation.
Elise Lebigot, Manuel Schiff, Marie-Pierre Golinelli-Cohen
Biomedicines, 2021 Aug 10, PMID: 34440194 PMCID: PMC8393393 DOI: 10.3390/biomedicines9080989

OTC deficiency in females: Phenotype-genotype correlation based on a 130-family cohort.
Stephanie Gobin-Limballe, Chris Ottolenghi, Fabien Reyal, Jean-Baptiste Arnoux, Maryse Magen, Marie Simon, Anaïs Brassier, Fabienne Jabot-Hanin, Pascale De Lonlay et al.
J Inherit Metab Dis, 2021 Sep, PMID: 34014569 DOI: 10.1002/jimd.12404

An Unusual Peak in a Common Clinical Presentation.
Bénédicte Sudrié-Arnaud, Sarah Snanoudj, Apolline Imbard, Ivana Dabaj, Abdellah Tebani
Clin Chem, 2021 Apr 29, PMID: 33928370 DOI: 10.1093/clinchem/hvab012

Adolescent-Onset and Adult-Onset Vitamin-Responsive Neurogenetic Diseases: A Review.
Daniele Mandia, Natalia Shor, Jean-François Benoist, Yann Nadjar
JAMA Neurol, 2021 Apr 1, PMID: 33427863 DOI: 10.1001/jamaneurol.2020.4911


Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.
Brassier A, Krug P, Lacaille F, Pontoizeau C, Krid S, Sissaoui S, Servais A, Arnoux JB, Legendre C, Charbit M, Scemla A, Francoz C, Benoist JF, Schiff M, Mochel F, Touati G, Broué P, Cano A, Tardieu M, Querciagrossa S, Grévent D, Boyer O, Dupic L, Oualha M, Girard M, Aigrain Y, Debray D, Capito C, Ottolenghi C, Salomon R, Chardot C, de Lonlay P. J Inherit Metab Dis. 2020 Mar;43(2):234-243. doi: 10.1002/jimd.12174. Epub 2020 Feb 11. PMID: 31525265

Infectious and digestive complications in glycogen storage disease type Ib: Study of a French cohort.
Wicker C, Roda C, Perry A, Arnoux JB, Brassier A, Castelle M, Servais A, Donadieu J, Bouchereau J, Pigneur B, Labrune P, Ruemmele FM, de Lonlay P. Mol Genet Metab Rep. 2020 Apr 9;23:100581. doi: 10.1016/j.ymgmr.2020.100581. eCollection 2020 Jun. PMID: 32300528 Free PMC article.

Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders.
Pontoizeau C, Roda C, Arnoux JB, Vignolo-Diard P, Brassier A, Habarou F, Barbier V, Grisel C, Abi-Warde MT, Boddaert N, Kuster A, Servais A, Kaminska A, Hennequin C, Dupic L, Lesage F, Touati G, Valayannopoulos V, Chadefaux-Vekemans B, Oualha M, Eisermann M, Ottolenghi C, de Lonlay P. Mol Genet Metab. 2020 Jun;130(2):110-117. doi: 10.1016/j.ymgme.2020.03.003. Epub 2020 Mar 19. PMID: 32273051

Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.
Bérat CM, Montealegre S, Wiedemann A, Nuzum MLC, Blondel A, Debruge H, Cano A, Chabrol B, Hoebeke C, Polak M, Stoupa A, Feillet F, Torre S, Boddaert N, Bruel H, Barth M, Damaj L, Abi-Wardé MT, Afenjar A, Benoist JF, Madrange M, Caccavelli L, Renard P, Hubas A, Nusbaum P, Pontoizeau C, Gobin S, van Endert P, Ottolenghi C, Maltret A, de Lonlay P. J Inherit Metab Dis. 2020 Sep 14. doi: 10.1002/jimd.12314. Online ahead of print. PMID: 32929747

Administration of gamma-hydroxybutyrate instead of beta-hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error.
Tuchmann-Durand C, Thevenet E, Moulin F, Lesage F, Bouchereau J, Oualha M, Khraiche D, Brassier A, Wicker C, Gobin-Limballe S, Arnoux JB, Lacaille F, Wicart C, Coat B, Schlattler J, Cisternino S, Renolleau S, Secretan PH, De Lonlay P. JIMD Rep. 2020 Jan 3;51(1):25-29. doi: 10.1002/jmd2.12090. eCollection 2020 Jan. PMID: 32071836 Free PMC article.

Long term outcome of MPI-CDG patients on D-mannose therapy.
Girard M, Douillard C, Debray D, Lacaille F, Schiff M, Vuillaumier-Barrot S, Dupré T, Fabre M, Damaj L, Kuster A, Torre S, Mention K, McLin V, Dobbelaere D, Borgel D, Bauchard E, Seta N, Bruneel A, De Lonlay P. J Inherit Metab Dis. 2020 Jul 17. doi: 10.1002/jimd.12289.

Long-Term Follow-up of a Child With Putative Remethylation Disorder Who Presented With Severe Anemia as a Neonate.
Zühre Kaya, Manuel Schiff, Jean-François Benoist
J Pediatr Hematol Oncol, 2020 May, PMID: 31789780 DOI: 10.1097/MPH.0000000000001689

Nocturnal enteral nutrition is therapeutic for growth failure in Fanconi-Bickel syndrome.
Alessandra Pennisi, Bruno Maranda, Jean-François Benoist, Véronique Baudouin, Odile Rigal, Samia Pichard, René Santer, Francesca Romana Lepri, Antonio Novelli, Hélène Ogier de Baulny, Carlo Dionisi-Vici, Manuel Schiff
J Inherit Metab Dis, 2020 May, PMID: 31816104 DOI: 10.1002/jimd.12203

Administration of gamma-hydroxybutyrate instead of beta-hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error.
Caroline Tuchmann-Durand,Eloise Thevenet,Florence Moulin,Fabrice Lesage,Juliette Bouchereau,Mehdi Oualha,Diala Khraiche,Anaïs Brassier,Camille Wicker,Stéphanie Gobin-Limballe,Jean-Baptiste Arnoux,Florence Lacaille,Clotilde Wicart,Bruno Coat,Joel Schlattler,Salvatore Cisternino,Sylvain Renolleau,Philippe-Henri Secretan,Pascale De Lonlay
JIMD Rep, 2020 Jan 3, PMID: 32071836 PMCID: PMC7012734 DOI: 10.1002/jmd2.12090

Nitrous oxide and vitamin B12 in sickle cell disease: Not a laughing situation.
Camille Desprairies, Apolline Imbard, Bérengère Koehl, Mathie Lorrot, Jean Gaschignard, Julie Sommet, Samia Pichard, Laurent Holvoet, Albert Faye, Malika Benkerrou, Jean-François Benoist, Manuel Schiff
Mol Genet Metab Rep, 2020 Mar 17, PMID: 32195121 PMCID: PMC7078522 DOI: 10.1016/j.ymgmr.2020.100579

[An acidosis not so basic].
Bertrand Lefrère, Emmanuelle Ecochard-Dugelay, Alexis Mosca, Jean-François Benoist, Jean-Pierre Hugot, Apolline Imbard
Ann Biol Clin (Paris), 2020 Aug 1, PMID: 32753366 DOI: 10.1684/abc.2020.1573

[Biochemical diagnosis of inherited metabolical diseases: metabolic profiles and difficulties for validating methods].
Jean-François Benoist, Roselyne Garnotel, Cécile Acquaviva Bourdain
Ann Biol Clin (Paris), 2020 Oct 1, PMID: 32933895 DOI: 10.1684/abc.2020.1584

Inherited Disorders of Lysine Metabolism: A Review.
Juliette Bouchereau, Manuel Schiff
J Nutr, 2020 Oct 1, PMID: 33000154 DOI: 10.1093/jn/nxaa112

Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
Alessandra Pennisi, Agnès Rötig, Charles-Joris Roux, Raphaël Lévy, Marco Henneke, Jutta Gärtner, Pelin Teke Kisa, Fatma Ceren Sarioglu, Uluç Yiş, Laura L Konczal, Deepika D Burkardt, Sulin Wu, Pauline Gaignard, Claude Besmond, Laurence Hubert, Marlène Rio, Giulia Barcia, Arnold Munnich, Nathalie Boddaert, Manuel Schiff
J Med Genet, 2020 Nov 16, PMID: 33199448 DOI: 10.1136/jmedgenet-2020-107367


Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening
Bower, A ; Imbard, A ; Benoist, JF ; Pichard, S ; Rigal, O ; Baud, O & al.
Sci Rep, 2019 Oct 1, PMID: 31575911 PMCID: PMC6773867 DOI: 10.1038/s41598-019-50518-0

Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency
Madeo, A ; Di Rocco, M ; Brassier, A ; Bahi-Buisson, N ; De Lonlay, P ; Ceballos-Picot, I.
Mol Genet Metab, 2019 Jun, PMID: 31182398 DOI: 10.1016/j.ymgme.2019.06.001

Lipin1 deficiency causes sarcoplasmic reticulum stress and chaperone-responsive myopathy
Rashid, T ; Nemazanyy, I ; Paolini, C ; Tatsuta, T ; Crespin, P ; de Villeneuve, D & al.
EMBO J, 2019 Jan 3, PMID: 30420558 PMCID: PMC6315296 DOI: 10.15252/embj.201899576

Elevated thrombin generation in patients with congenital disorder of glycosylation and combined coagulation factor deficiencies
Pascreau, T ; de la Morena-Barrio, ME ; Lasne, D ; Serrano, M ; Bianchini, E ; Kossorotoff, M & al.
J Thromb Haemost, 2019 Nov, PMID: 31271700 DOI: 10.1111/jth.14559

International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up
Altassan, R ; Péanne, R ; Jaeken, J ; Barone, R ; Bidet, M ; Borgel, D & al.
J Inherit Metab Dis, 2019 Jan, PMID: 30740725 DOI: 10.1002/jimd.12024


Long-term liver disease in methylmalonic and propionic acidemias
Imbard, A ; Garcia Segarra, N ; Tardieu, M ; Broué, P ; Bouchereau, J ; Pichard, S & al.
Mol Genet Metab, 2018 Apr, PMID: 29433791 DOI: 10.1016/j.ymgme.2018.01.009


Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability
Anikster, Y ; Haack, TB ; Vilboux, T ; Pode-Shakked, B ; Thöny, B ; Shen, N & al.
Am J Hum Genet, 2017 Feb 2, PMID: 28132689 PMCID: PMC5294665 DOI: 10.1016/j.ajhg.2017.01.002

Neurocognitive profiles in MSUD school-age patients
Bouchereau, J ; Leduc-Leballeur, J ; Pichard, S ; Imbard, A ; Benoist, JF ; Abi Warde, MT & al.
J Inherit Metab Dis, 2017 May, PMID: 28324240 DOI: 10.1007/s10545-017-0033-7


Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency
Olsen, RKJ ; Koňaříková, E ; Giancaspero, TA ; Mosegaard, S ; Boczonadi, V ; Mataković, L & al.
Am J Hum Genet, 2016 Jun 2, PMID: 27259049 PMCID: PMC4908180 DOI: 10.1016/j.ajhg.2016.04.006

8th French day on Pompe disease | Institut Imagine | 3.30.2018
> What was said is here (in French)

Newborn screening: MCAD deficiency, a sixth disease detected at birth
Le Parisien | 12.14.2020
As of December 1, all newborns are screened for medium chain fatty acid acyl-CoA dehydrogenase (MCAD) deficiency. This is in addition to the five other conditions already screened for.
> Read more

Contact information

Necker-Enfants malades university hospital
> Pediatric metabolic diseases

149 rue de Sèvres
75743 PARIS Cedex 15

> Pediatric welcome booklet

In Necker, the MAMEA reference center in brief 

patients followed at least once a year*
medical consultations*
day hospitalizations*
fully hospitalized patients*
authorized therapeutic education programs*
patients trained in therapeutic education*
current research projects*
university courses*
teleconsultation procedures*

* data valid for 2021