Klinische FragestellungMentale Retardierung bei Stoffwechsel-Störungen, Differentialdiagnose

NGS +

[Sanger]

Mentale Retardierung (akzeptierter englischer Begriff, „intellectual deficits“) ist ein lebenslang schwächender Zustand, der bis zu 2-3% der Bevölkerung in westlichen Ländern betrifft. Während die kausale Pathogenese extrem unterschiedlich ist, stellen bei >50% der Patienten genetische Ätiologien die häufigste Ursache dar. Dieser Prozentsatz nimmt angesichts von effizienten NGS-Technologien zu. Beinahe 6% der Kinder mit intellektuellem Defizit haben eine von >500 ererbte Stoffwechselstörungen. Die meisten davon werden durch einen genetischen Mangel eines Enzyms verursacht, das zur Umwandlung eines Moleküls in ein anderes benötigt wird. Angeborene Stoffwechselstörungen stellen die größte Kategorie von genetischen Erkrankungen dar, die für eine kausale Therapie in Frage kommen. Die meisten Stoffwechselstörungen werden autosomal rezessiv vererbt. DNA-diagnostische Ausbeuten für Stoffwechsel-Störungen sind sehr unterschiedlich und derzeit nicht zusammenfassend anzugeben. Die klinische Diagnose kann durch ein negatives molekulargenetisches Ergebnis keinesfalls ausgeschlossen werden.

• Alias: Intellectual deficit, inborn error of metabolism
• Alias: Intellectual disability, inborn error of metabolism
• Alias: Intellectual disability, metabolic disorder
• Alias: Psycho-motor retardation, inborn error of metabolism
• Alias: Psycho-motor retardation, metabolic disorder
• 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement + neutropenia (CLPB)
• AICA-ribosiduria due to ATIC deficiency (ATIC)
• Adenylosuccinase deficiency (ADSL)
• Aicardi-Goutieres syndrome 1, dominant + recessive (TREX1)
• Allelic: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 (DPM3)
• Allelic: Myasthenic syndrome, congenital, 13, with tubular aggregates (DPAGT1)
• Allelic: Occipital horn syndrome (ATP7A)
• Allelic: Polycystic liver disease 3 with/-out kidney cysts (ALG8)
• Allelic: Spinal muscular atrophy, distal, XL 3 (ATP7A)
• Allelic: Systemic lupus erythematosus, susceptibility to (TREX1)
• Aminoacylase 1 deficiency (ACY1)
• Aromatic L-amino acid decarboxylase deficiency (DDC)
• CHIME syndrome (PIGL)
• Canavan disease (ASPA)
• Cerebral creatine deficiency syndrome 1 (SLC6A8)
• Ceroid lipofuscinosis, neuronal, 2 (TPP1)
• Chilblain lupus (TREX1)
• Congenital disorder of deglycosylation (NGLY1)
• Congenital disorder of glycosylation, type IIa (MGAT2)
• Congenital disorder of glycosylation, type IIb (MOGS)
• Congenital disorder of glycosylation, type IIc (SLC35C1)
• Congenital disorder of glycosylation, type IId (BGALT1)
• Congenital disorder of glycosylation, type IIe (COG7)
• Congenital disorder of glycosylation, type IIf (SLC35A1)
• Congenital disorder of glycosylation, type IIg (COG1)
• Congenital disorder of glycosylation, type IIh (COG8)
• Congenital disorder of glycosylation, type IIi (COG5)
• Congenital disorder of glycosylation, type IIj (COG4)
• Congenital disorder of glycosylation, type IIk (TMEM165)
• Congenital disorder of glycosylation, type IIl (COG6)
• Congenital disorder of glycosylation, type IIm (SLC35A2)
• Congenital disorder of glycosylation, type Ia (PMM2)
• Congenital disorder of glycosylation, type Ib (MPI)
• Congenital disorder of glycosylation, type Id (ALG3)
• Congenital disorder of glycosylation, type Id (ALG6)
• Congenital disorder of glycosylation, type Ie (DPM1)
• Congenital disorder of glycosylation, type If (MPDU1)
• Congenital disorder of glycosylation, type Ig (ALG12)
• Congenital disorder of glycosylation, type Ih (ALG8)
• Congenital disorder of glycosylation, type Ij (DPAGT1)
• Congenital disorder of glycosylation, type Ik (ALG1)
• Congenital disorder of glycosylation, type Il (ALG9)
• Congenital disorder of glycosylation, type Im (DOLK)
• Congenital disorder of glycosylation, type In (RFT1)
• Congenital disorder of glycosylation, type Ip (ALG11)
• Congenital disorder of glycosylation, type Iq (SRD5A3)
• Congenital disorder of glycosylation, type Ir (DDOST)
• Congenital disorder of glycosylation, type Is (ALG13)
• Congenital disorder of glycosylation, type It (PGM1)
• Congenital disorder of glycosylation, type Iu (DPM2)
• Congenital disorder of glycosylation, type Iw (STT3A)
• Congenital disorder of glycosylation, type Iy (SSR4)
• Danon disease (LAMP2)
• Desmosterolosis (DHCR24)
• Developmental + epileptic encephalopathy 15 (ST3GAL3)
• Developmental + epileptic encephalopathy 36 (ALG13)
• Developmental + epileptic encephalopathy 71 (GLS)
• Dystonia 9 (SLC2A1)
• Dystonia, DOPA-responsive, with or without hyperphenylalaninemia (GCH1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Farber lipogranulomatosis (ASAH1)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Galactose epimerase deficiency (GALE)
• Galactosemia (GALT)
• Gillessen-Kaesbach-Nishimura syndrome (ALG9)
• Global developmental delay, progressive ataxia, elevated glutamine (GLS)
• Glutaricaciduria, type I (GCDH)
• Glycosylphosphatidylinositol biosynthesis defect 11 (PIGW)
• Hyperphenylalaninemia, BH4-deficient, A (PTS)
• Hyperphenylalaninemia, BH4-deficient, B (GCH1)
• Hyperphenylalaninemia, BH4-deficient, C (QDPR)
• Hyperphosphatasia with mental retardation syndrome 1 (PIGV)
• Hyperphosphatasia with mental retardation syndrome 2 (PIGO)
• Hyperphosphatasia with mental retardation syndrome 3 (PGAP2)
• Hyperphosphatasia with mental retardation syndrome 4 (PGAP3)
• Hyperprolinemia, type II (ALD4A1)
• Infantile cataract, skin abnormalities, glutamate excess, impaired intellectual development (GLS)
• Intellectual developmental disorder, AR 12 (ST3GAL3)
• Kahrizi syndrome (SRD5A3)
• Lathosterolosis (SC5D)
• Menkes disease (ATP7A)
• Mucopolysaccharidosis II (IDS)
• Muscular dystrophy-dystroglycanopathy (cong. with impaired intell. development), type B, 15 (DPM3)
• Neurodegeneration with brain iron accumulation 5 (WDR45)
• Nicotine dependence, protection against (SLC6A3)
• Ornithine transcarbamylase deficiency (OTC)
• Orotic aciduria (UMPS)
• Parkinsonism-dystonia, infantile, 1 (SLC6A3)
• Phosphoglycerate kinase 1 deficiency (PGK1)
• Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
• Saul-Wilson syndrome (COG4)
• Segawa syndrome, recessive (TH)
• Shaheen syndrome (COG6)
• Sjogren-Larsson syndrome (ALH3A2)
• Smith-Lemli-Opitz syndrome (DHCR7)
• Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)
• Spinocerebellar ataxia, AR 7 (TPP1)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Succinic semialdehyde dehydrogenase deficiency (ALDH5A1)
• Transcobalamin II deficiency (TCN2)
• Tyrosinemia, type II (TAT)
• Vasculopathy, retinal, with cerebral leukoencephalopathy + systemic manifestations (TREX1)