Klinische FragestellungAceruloplasminämie, Differentialdiagnose

NGS + X

Bei der Aceruloplasminämie reichert sich Eisen allmählich im Gehirn (und anderen Organen) an, was im Erwachsenenalter zu neurologischen Problemen führt. Bewegungsstörungen (Zittern, Dystonie, Chorea, Blepharospasmen, Ataxie usw.) verschlimmern sich mit der Zeit. Einige Patienten entwickeln nach dem vierzigsten Lebensjahr psychiatrische Probleme und Demenz. Diabetes mellitus wird durch Ablagerungenen im Pankreas verursacht und Netzhaut-Atrophie durch lokalen Eisenüberschuss. Die Eisenansammlung in den Organen führt zum Mangel im Blut und Anämie in den zwanziger Jahren. Die spezifischen Merkmale der Aceruloplasminämie und der Schweregrad können selbst innerhalb derselben Familie variieren. Die Erkrankung wird autosomal-rezessiv über Mutationen im CP-Gen vererbt. Die molekulargenetische Ausbeute übersteigt 95% bei japanischen Patienten mit schwach ausgeprägten Arealen sowohl in den Basalganglien als auch in der Leber im MRT. Daher ist die klinische Diagnose nicht immer durch einen DNA-Test gesichert, und differentialdiagnostisch sind viele Gene zu berücksichtigen.

Gene (###)

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1493/

• Alias: Aceruloplasminemia
• Alias: Azeruloplasminämie
• Alias: Deficiency of ferroxidase
• Alias: Hereditary ceruloplasmin deficiency (CP)
• Allelic: Arthrogryposis multiplex congenita 3, myogenic type (SYNE1)
• Allelic: Arthrogryposis multiplex congenita 5 (TOR1A)
• Allelic: Brugada syndrome 9 (KCND3)
• Allelic: Cataract 41 (WFS1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2T (MME)
• Allelic: Charcot-Marie-Tooth disease, type 2B2 (PNKP)
• Allelic: Combined oxidative phosphorylation deficiency 25 (MARS2)
• Allelic: Deafness, AD 6/14/38 (WFS1)
• Allelic: Emery-Dreifuss muscular dystrophy 4, AD (SYNE1)
• Allelic: Enlarged vestibular aqueduct, digenic (KCNJ10)
• Allelic: Fragile X syndrome (FLVCR1)
• Allelic: Hydrocephalus, congenital, 1 (CCDC88C)
• Allelic: Hyperaldosteronism, familial, type II (CLCN2)
• Allelic: Hyperferritinemia-cataract syndrome (FTL)
• Allelic: Ichthyosis, spastic quadriplegia + mental retardation (ELOVL4)
• Allelic: Lopes-Maciel-Rodan syndrome (HTT)
• Allelic: Migraine, familial hemiplegic, 1 (CACNA1A)
• Allelic: Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Allelic: Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
• Allelic: Mitochondrial DNA depletion syndrome 4B, MNGIE type (POLG)
• Allelic: Myasthenic syndrome, congenital, 25 (VAMP1)
• Allelic: Myopathy, distal, with rimmed vacuoles (SQSTM1)
• Allelic: Neuropathy, hereditary motor + sensory, type VIB ((SLC25A46)
• Allelic: Neuropathy, hereditary sensory, type IE (DNMT1)
• Allelic: Optic atrophy 12 (AFG3L2)
• Allelic: Optic atrophy 9 (ACO2)
• Allelic: Paget disease of bone 3 (SQSTM1)
• Allelic: Pancreatic agenesis 2 (PTF1A)
• Allelic: Perrault syndrome 5 (TWNK)
• Allelic: Premature ovarian failure 1 (FLVCR1)
• Allelic: Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
• Allelic: Progressive external ophthalmoplegia, AD 1 (POLG)
• Allelic: Progressive external ophthalmoplegia, AR 1 (POLG)
• Allelic: Rhizomelic chondrodysplasia punctata, type 1 (PEX7)
• Allelic: Seizures, benign familial infantile, 2 (PRRT2)
• Allelic: Seizures, benign familial infantile, 3 (SCN2A)
• Allelic: Stargardt disease 3 (ELOVL4)
• Alternating hemiplegia of childhood 2 (ATP1A3)
• Amyotrophic lateral sclerosis 4, juvenile (SETX)
• Anemia, sideroblastic, with ataxia (ABCB7)
• Ataxia with isolated vitamin E deficiency (TTPA)
• Ataxia, cerebellar, Cayman type (ATCAY)
• Ataxia, early-onset, with oculomotor apraxia + hypoalbuminemia (APTX)
• Ataxia, posterior column, with retinitis pigmentosa (FLVCR1)
• Ataxia-oculomotor apraxia 4 (PNKP)
• Ataxia-telangiectasia (ATM)
• Boucher-Neuhauser syndrome (PNPLA6)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• CAPOS syndrome, Cereb. ataxia, Areflexia, Pes cavus, optic atrophy, sensorin. hear loss (ATP1A3)
• Cerebellar ataxia (CP)
• Cerebellar ataxia + hypogonadotropic hypogonadism (RNF216)
• Cerebellar ataxia, deafness + narcolepsy, AD (DNMT1)
• Cerebellar ataxia, mental retardation + dysequilibrium syndrome 4 (ATP8A2)
• Cerebellar ataxia, neuropathy + vestibular areflexia syndrome (RFC1)
• Cerebellar hypoplasia + mental retardation with/-out quadrupedal locomotion 1 (VLDLR)
• Cerebrotendinous xanthomatosis (CYP27A1)
• Ceroid lipofuscinosis, neuronal, 2 (TPP1)
• Ceroid lipofuscinosis, neuronal, 5 (CLN5)
• Coenzyme Q10 deficiency, primary, 4 (COQ8A)
• Combined oxidative phosphorylation deficiency 29 (TXN2)
• Combined oxidative phosphorylation deficiency 3 (TSFM)
• Congenital hypotonia, epilepsy, developmental delay + digital anomalies (ATN1)
• Convulsions, familial infantile, with paroxysmal choreoathetosis (PRRT2)
• Dentatorubral-pallidoluysian atrophy (ATN1)
• Developmental + epileptic encephalopathy 11 (SCN2A)
• Developmental + epileptic encephalopathy 28 (WWOX)
• Developmental + epileptic encephalopathy 42 (CACNA1A)
• Developmental + epileptic encephalopathy 44 (UBA5)
• Developmental + epileptic encephalopathy 47 (FGF12)
• Developmental + epileptic encephalopathy 99 (ATP1A3)
• Diencephalic-mesencephalic junction dysplasia syndrome 1 (PCDH12)
• Dystonia 16 (PRKRA)
• Dystonia 24 (ANO3)
• Dystonia 25 (GNAL)
• Dystonia 4, torsion, AD (TUBB4A)
• Dystonia 6, torsion (THAP1)
• Dystonia 9 (SLC2A1)
• Dystonia, DOPA-responsive, with/-out hyperphenylalaninemia (GCH1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Dystonia-1, torsion (TOR1A)
• Dystonia-11, myoclonic (SGCE)
• Dystonia-12 (ATP1A3)
• Dystonia-Parkinsonism, XL (TAF1)
• Epilepsy, progressive myoclonic 6 (GOSR2)
• Episodic ataxia, type 2 (CACNA1A)
• Episodic ataxia, type 5 (CACNB4)
• Episodic ataxia, type 6 (SLC1A3)
• Episodic ataxia, type 9 (SCN2A)
• Episodic ataxia/myokymia syndrome (KCNA1)
• Episodic kinesigenic dyskinesia 1 (PRRT2)
• FG syndrome 4 (CASK)
• Familial apoceruloplasmin deficiency (CP)
• Fragile X tremor/ataxia syndrome (FLVCR1)
• Friedreich ataxia (FXN)
• Friedreich ataxia with retained reflexes (FXN)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (TWNK)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (SQSTM1)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Galloway-Mowat syndrome 1 (WDR73)
• Gillespie syndrome (ITPR1)
• HARP [hypoprebetalipoproteinemia, acanthocytosis, RP + pallidal degeneration] syndrome (PANK2)
• Hemochromatosis (HFE)
• Hemosiderosis, systemic, due to aceruloplasminemia (CP)
• Huntington disease (HTT)
• Hyperphenylalaninemia, BH4-deficient, B (GCH1)
• Hypoceruloplasminemia, hereditary (CP)
• Infantile cerebellar-retinal degeneration (ACO2)
• Intellectual developmental disorder + microcephaly with pontine + cerebellar hypoplasia (CASK)
• Intellectual developmental disorder, XL syndromic 33 (TAF1)
• Intellectual developmental disorder, XL syndromic, Billuart type (OPHN1)
• Intellectual developmental disorder, XL syndromic, Christianson type (SLC9A6)
• Kabuki syndrome 1 (KMT2D)
• L-ferritin deficiency, AD + AR (FTL)
• Laurence-Moon syndrome (PNPLA6)
• Leukodystrophy, hypomyelinating, 14 (UFM1)
• Leukodystrophy, hypomyelinating, 6 (TUBB4A)
• Leukodystrophy, hypomyelinating, 7, with/-out oligodontia +/- hypogonadotropic hypogonadism (POLR3A)
• Leukodystrophy, hypomyelinating, 8, with/-out oligodontia +/- hypogonadotropic hypogonadism (POLR3B)
• Leukoencephalopathy with ataxia (CLCN2)
• Lichtenstein-Knorr syndrome (SLC9A1)
• Machado-Joseph disease (ATXN3)
• Marinesco-Sjogren syndrome (SIL1)
• Mental retardation, with/-out nystagmus (CASK)
• Microcephaly, seizures + developmental delay (PNKP)
• Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
• Mitochondrial recessive ataxia syndrome, includes SANDO + SCAE (POLG)
• Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1)
• Neurodegeneration with ataxia, dystonia + gaze palsy, childhood-onset (SQSTM1)
• Neurodegeneration with brain iron accumulation 1 (PANK2)
• Neurodegeneration with brain iron accumulation 3 (FTL)
• Oliver-McFarlane syndrome (PNPLA6)
• Pancreatic + cerebellar agenesis (PTF1A)
• Paroxysmal nonkinesigenic dyskinesia 1 (PNKD)
• Peroxisome biogenesis disorder 9B (PEX7)
• Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa + cataract (ABHD12)
• Pontocerebellar hypoplasia, type 1E (SLC25A46)
• Poretti-Boltshauser syndrome (LAMA1)
• Refsum disease (PHYH)
• SESAME syndrome (KCNJ10)
• Segawa syndrome, AR (TH)
• Slowly progressive cerebellar ataxia, ID, seizures, episodic pain [panelapp] (MTCL1)
• Spastic ataxia 1, AD (VAMP1)
• Spastic ataxia 2, AR (KIF1C)
• Spastic ataxia 3, AR (MARS2)
• Spastic ataxia 4, AR (MTPAP)
• Spastic ataxia 5, AR (AFG3L2)
• Spastic ataxia, Charlevoix-Saguenay type (SACS)
• Spastic paraplegia 39, AR (PNPLA6)
• Spastic paraplegia 7, AR (SPG7)
• Spastic paraplegia 76, AR (CAPN1)
• Spinocerebellar ataxia 1 (ATXN1)
• Spinocerebellar ataxia 10 (ATXN10)
• Spinocerebellar ataxia 11 (TTBK2)
• Spinocerebellar ataxia 12 (PP2R2B)
• Spinocerebellar ataxia 13 (KCNC3)
• Spinocerebellar ataxia 14 (PRKCG)
• Spinocerebellar ataxia 15 (ITPR1)
• Spinocerebellar ataxia 17 (TBP)
• Spinocerebellar ataxia 19 (KCND3)
• Spinocerebellar ataxia 2 (ATXN2)
• Spinocerebellar ataxia 21 (TMEM240)
• Spinocerebellar ataxia 23 (PDYN)
• Spinocerebellar ataxia 26 (EEF2)
• Spinocerebellar ataxia 27 (FGF14)
• Spinocerebellar ataxia 28 (AFG3L2)
• Spinocerebellar ataxia 29, congenital nonprogressive (ITPR1)
• Spinocerebellar ataxia 31 (BEAN1)
• Spinocerebellar ataxia 34 (ELOVL4)
• Spinocerebellar ataxia 35 (TGM6)
• Spinocerebellar ataxia 36 (NOP56)
• Spinocerebellar ataxia 38 (ELOVL5)
• Spinocerebellar ataxia 40 (CCDC88C)
• Spinocerebellar ataxia 41 (TRPC3)
• Spinocerebellar ataxia 42 (CACNA1G)
• Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (CACNA1G)
• Spinocerebellar ataxia 43 (MME)
• Spinocerebellar ataxia 44 (GRM1)
• Spinocerebellar ataxia 45 (FAT2)
• Spinocerebellar ataxia 46 (PLD3)
• Spinocerebellar ataxia 47 (PUM1)
• Spinocerebellar ataxia 48 (STUB1)
• Spinocerebellar ataxia 5 (SPTNB2)
• Spinocerebellar ataxia 6 (CACNA1A)
• Spinocerebellar ataxia 7 (ATXN7)
• Spinocerebellar ataxia, AR 10 (ANO10)
• Spinocerebellar ataxia, AR 11 (SYT14)
• Spinocerebellar ataxia, AR 12 (WWOX)
• Spinocerebellar ataxia, AR 13 (GRM1)
• Spinocerebellar ataxia, AR 14 (SPTBN2)
• Spinocerebellar ataxia, AR 15 (RUBCN)
• Spinocerebellar ataxia, AR 16 (STUB1)
• Spinocerebellar ataxia, AR 17 (CWF19L1)
• Spinocerebellar ataxia, AR 18 (GRID2)
• Spinocerebellar ataxia, AR 2 (PMPCA)
• Spinocerebellar ataxia, AR 20 (SNX14)
• Spinocerebellar ataxia, AR 22 (VWA3B)
• Spinocerebellar ataxia, AR 23 (TDP2)
• Spinocerebellar ataxia, AR 24 (UBA5)
• Spinocerebellar ataxia, AR 25 (ATG5)
• Spinocerebellar ataxia, AR 27 (GDAP2)
• Spinocerebellar ataxia, AR 4 (VPS13D)
• Spinocerebellar ataxia, AR 7 (TPP1)
• Spinocerebellar ataxia, AR 8 (SYNE1)
• Spinocerebellar ataxia, AR, with axonal neuropathy 1 (TDP1)
• Spinocerebellar ataxia, AR, with axonal neuropathy 2 (SETX)
• Spinocerebellar ataxia, XL 1 (ATP2B3)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Wiedemann-Rautenstrauch syndrome (POLR3A)
• Wilson disease (ATP7B)
• Wolfram syndrome 1 (WFS1)
• Wolfram-like syndrome, AD (WFS1)