Cardiovascular System |
Arrhythmias, conduction defects (heart beat disorders) |
Primitive heartbeat disorders |
Adrenal dysfunction (hyperkalemia) |
AMP activated protein kinase (PRKAG2: WPW) |
Cardiac glycogenosis (Wolf Parkinson White:
WPW) |
Triose phosphate isomerase deficiency |
D2-hydroxyglutaric aciduria (AV block) |
Fatty acid oxidation disorders (CPT
II, carnitine translocase, LCAD, LCHAD, TF, VLCAD) |
Hypoparathyroidism (hypocalcemia) |
Kearn-Sayre syndrome (respiratory-chain disorders) |
Thiamine deficiency-dependent states (cardiomyopathy,
cardiac with multiorgan failure) |
Cardiac failure, collapse |
With tamponade, multiorgan failure: |
Carbohydrate deficient glycoprotein syndrome |
With heartbeat disorders (see below) |
With cardiomyopathy (see below) |
Cardiomyopathy |
AMP activated protein kinase (and NOT phosphorylase-b-kinase)
(presenting sign)18 |
Barth syndrome |
Carbohydrate-deficient glycoprotein syndrome (with pericardial
effusion, can be the presenting sign) |
Congenital muscle dystrophies |
D-2-hydroxyglutaric aciduria |
Fabry disease |
Fatty acid oxidation disorders (presenting sign) |
Friedreich ataxia (presenting sign) |
Glycogenosis type III and IV |
GM1 gangliosidosis |
Isobutyryl-CoA dehydrogenase |
Methylmalonic aciduria (Cbl C), Malonic aciduria |
Mucopolysaccharidosis |
Muscular glycogen synthetase (presenting sign)32 |
Pompe disease, Danon disease (presenting sign) |
Propionic acidemia |
Respiratory-chain disorders (presenting sign) |
Selenium deficiency |
Steinert disease—myotonic dystrophy |
Thiamine deficiency |
Thiamine responsive anemia |
3-methylglutaconic aciduria |
Skin |
Acrocyanosis (orthostatic) |
EPEMA syndrome |
Alopecia |
Age at onset: neonatal to infancy |
Acrodermatitis enteropathica |
Biotin-responsive multiple carboxylase defects |
Calciferol metabolism defects (vitamin-D-dependent
rickets) |
Congenital erythropoietic porphyria |
Conradi-Hunermann syndrome |
Ehlers-Danlos type IV |
Essential fatty acid deficiency |
Hepatoerythropoietic porphyria |
Menkes disease (X-linked) |
Methylmalonic and propionic acidurias |
Netherton syndrome |
Zinc deficiency |
Age at onset: Adulthood |
Porphyria cutanea tarda |
Angio keratosis |
Aspartylglycosaminuria |
β-mannosidosis |
Fabry disease (presenting sign) |
Fucosidosis |
Galactosialidosis |
Kanzaki disease |
Schindler disease (adult form) |
Brittle hair |
Argininosuccinic aciduria |
Citrullinemia |
Menkes syndrome |
Pollitt syndrome |
Trichothiodystrophy |
Hyperkeratosis |
CEDNIK (neuro-cutaneous syndrome: keratosis
on palms and soles)17 |
Ichthyosis |
Tyrosinemia type II (keratosis on palms and
soles) |
Ichthyosis (with congenital erythroderma) |
Austin disease (multisulfatases deficiency) |
CDG If (with chondrodysplasia punctata) |
CEDNIK (neuro-cutaneous syndrome: SNARE protein
mutation)17 |
Conradi-Hunermann syndrome (chondrodysplasia
punctata X-linked) |
Multisystemic triglyceride storage disease |
Refsum disease (adult form) |
Serine deficiency syndrome |
Sjögren-Larsson syndrome |
Steroid sulfatase deficiency (X-linked) |
Laxity (Dysmorphic scarring, easy bruising) |
Inborn errors of collagen: Ehlers-Danlos syndrome
(nine types) |
Occipital horn syndrome |
Pyrroline-5-carboxylate synthetase |
Nodules |
Carbohydrate-deficient glycoprotein syndrome |
Farber lipogranulomatosis |
Pellagra |
Hartnup disease |
Photosensitivity and skin rashes |
Age at onset: neonatal to childhood |
Congenital erythropoietic porphyria |
Erythrohepatic porphyria |
Erythropoietic protoporphyria |
Hartnup disease |
Mevalonic aciduria (with fever and arthralgia) |
Respiratory-chain disorders |
Age at onset: adulthood |
Hereditary coproporphyria |
Porphyria variegata |
Porphyria cutanea tarda |
Pili torti |
Menkes disease |
Netherton syndrome |
Telangiectasias, purpuras, petechiae |
Ethylmalonic aciduria (EPEMA syndrome) |
Prolidase deficiency |
Trichorrhexis nodosa |
Argininemia |
Argininosuccinic aciduria |
Lysinuric protein intolerance |
Menkes disease |
Netherton syndrome |
Ulceration (skin ulcers) |
Prolidase deficiency |
Vesiculo bullous skin lesions |
Acrodermatitis enteropathica |
Biotinidase deficiency (biotin-responsive) |
Holocarboxylase synthetase deficiency (biotin-responsive) |
Methylmalonic, propionic acidemias (isoleucine
deficiency) |
Zinc deficiency |
Xanthoma |
Apo CII (eruptive) |
Apolipoprotein A1 (planar) |
Autosomal dominant hypercholesterolemia |
Autosomal recessive hypercholesterolemia (childhood) |
Dysbetalipoproteinemia (hyperlipoproteinemia
type III) |
Hepatic lipase |
Lipoprotein lipase (eruptive) |
Sitosterolemia (childhood) |
Dysmorphology |
Coarse Facies |
Age at onset: present at birth |
Galactosialidosis (early infancy) |
I-cell disease |
Landing |
Sialidosis type II |
Sly (mucopolysaccharidosis (MPS) type VII) (rare) |
Age at onset: early infancy |
Austin |
Fucosidosis type I |
Hurler (MPS type Is) |
Mannosidosis |
Maroteaux-Lamy (MPS type V) |
Salla disease |
Sialidosis type II |
Sly (MPS type VII) |
Age at onset: childhood |
Aspartylglycosaminuria |
Hunter (MPS type II) |
Pseudo-Hurler polydystrophy |
San Filippo syndrome (MPS type III) |
Dysplasia, dysmorphia |
Maternal metabolic disturbances (untreated pregnancy) |
PKU (dysmaturity, heart defect, microcephaly,
special face, hypotrophy) |
Alcohol (dysmorphia, hypotrophy) |
Diabetes (macrosomia) |
Drugs (dysmorphia, hypotrophy) |
Vitamin deficiencies (riboflavin) |
Inborn errors affecting the fetus |
Carnitine palmityl transferase II deficiency
(renal cysts) |
D-2-hydroxyglutaric aciduria |
Glutaric aciduria II (MADD; renal cysts) |
Inborn errors of collagen |
Hyperinsulinism (macrosomia, dysmorphia) |
Hypoparathyroidism |
Hypophosphatasia |
Leprechaunism |
Lysosomal storage disorders (hydrops fetalis) |
Mevalonic aciduria (mevalonate kinase deficiency) |
Peroxisomal biogenesis defects (renal cysts,
neuronal migration defects) |
Chondrodysplasia punctata |
Pyruvate dehydrogenase deficiency |
Respiratory-chain defects |
Transaldolase deficiency (hydrops fetalis) |
Malformations |
3-OH-isobutyryl-CoA deacylase deficiency (limbs,
vertebrae) |
Cholesterol synthesis defects |
Nonketotic hyperglycinemia |
O-glycosylation and related defects |
Respiratory-chain disorders |
Intrauterine growth retardation |
Alcoholic fetal syndrome |
Infants born to mothers with untreated phenylketonuria |
Cholesterol biosynthesis defects |
Lysosomal storage disorders |
Many nonmetabolic polymalformative syndromes |
Peroxisomal disorders |
Respiratory-chain disorders |
Transaldolase deficiency |
Endocrine system |
Diabetes (and Pseudodiabetes) |
Abnormal pro-insulin cleavage |
Diabetes, deafness, and thiamine responsive
megaloblastic anemia |
Diabetes type II: fatty acid oxidation disorders
?, glucokinase |
Organic acidurias (methylmalonic, propionic,
isovaleric acidemias, ketolytic defects) |
Respiratory-chain disorders—Wolfram
syndrome |
Hyperinsulinism |
SUR1 and Kir6.2 mutations (potassium channel) |
Glucokinase overactivity |
Glutamate dehydrogenase overactivity |
Short-chain L-3-OH-acyl-CoA dehydrogenase |
Wiedemann-Beckwith syndrome |
Hyperthyroidism |
Glutaric aciduria (glutaryl-CoA oxidase deficiency
?) |
Hypogonadism: sterility |
CDG syndrome type I |
Galactosemia |
Hypoparathyroidism |
Long-chain 3-hydroxylacyl-CoA dehydrogenase
deficiency |
Respiratory-chain disorders |
Trifunctional enzyme deficiency |
Hypothyroidism |
Allan-Herndon-Dudley syndrome (monocarboxylate
transporter 8)22 |
Salt-losing syndrome |
Disorders of adrenal steroid metabolism |
Fatty acid oxidation disorders (carnitine palmityl
transferase II) |
Respiratory-chain disorders (mitochondrial DNA
deletions) |
Sexual ambiguity |
Congenital adrenal hyper- and hypoplasia |
Disorders of adrenal steroid metabolism |
Short stature: growth hormone deficiency |
Respiratory-chain disorders |
Gastrointestinal System |
Abdominal pain (recurrent) |
With flatulence, diarrhea, loose stools |
Lactose malabsorption |
Congenital sucrase isomaltase deficiency |
With vomiting, lethargy, ketoacidosis |
Urea cycle defects (OTC, ASA) |
Organic acidurias (MMA, PA, IVA) |
Ketolysis defects |
Respiratory-chain disorders |
Diabetes |
With neuropathy, psychiatric symptoms |
Porphyrias |
Tyrosinemia type I |
OTC (late onset) |
With hepatomegaly and splenomegaly |
Cholesterol ester storage disease |
Lipoprotein lipase deficiency |
Lysinuric protein intolerance |
Hemochromatosis |
Mevalonate kinase deficiency |
With pain in extremities |
Fabry disease |
δ-aminolevulinate dehydratase
deficiency |
Sickle cell anemia |
With hemolytic anemia |
Coproporphyria |
Hereditary spherocytosis |
Sickle cell anemia |
Nocturnal paroxysmal hemoglobinuria |
With Crohn disease |
Trifunctional enzyme ? |
Carnitine transporter (OCTN2) |
With inflammatory syndrome (fever rash, IC reactive protein) |
Hyper-IgD syndrome (mevalonate kinase deficiency) |
Acute pancreatitis |
Hyperlipoproteinemia type I and IV |
Lysinuric protein intolerance |
Organic acidurias (MMA, PA, IVA, MSUD) |
Respiratory-chain disorders (Pearson, MELAS) |
Chronic diarrhea, failure to thrive, osteoporosis |
Hypocholesterolemia |
Abetalipoproteinemia type I and II |
Carbohydrate-deficient glycoprotein syndromes
type I |
Infantile Refsum disease |
Mevalonic aciduria |
Peroxisomal disorders |
Smith-Lemli-Opitz syndrome |
Tangier disease (alpha-lipoprotein deficiency) |
HELLP syndrome (baby born to mothers with) |
Carnitine palmityl transferase I deficiency |
LCHAD deficiency and other fatty acid β-oxidation
disorders |
Respiratory-chain defects |
Intestinal obstruction |
MNGIE syndrome (mitochondrial cytopathy) |
Blood |
Acanthocytosis |
Abetalipoproteinemia |
Hallervorden-Spatz syndrome (pantothenate kinase) |
Inborn errors of cobalamin (Cbl C) |
Wolman disease |
Anemias (macrocytic) |
Hereditary orotic aciduria |
Inborn errors of cobalamin metabolism |
Imerslund disease |
Intrinsic factor deficiency |
TC II deficiency |
Cbl C, Cbl E, Cbl G |
Methionine synthase deficiency |
Inborn errors of folate metabolism |
Dihydrofolate reductase deficiency |
Glutamate formimino transferase deficiency |
Congenital folate malabsorption |
Mevalonic aciduria |
Pearson syndrome (due to mitochondrial DNA deletion;
dyserythropoiesis) |
Respiratory-chain disorders |
Thiamine responsive megaloblastic anemia |
Anemias (Nonmacrocytic, hemolytic, or due to combined mechanisms) |
Abetalipoproteinemia |
Carnitine transport defect |
Congenital erythropoietic porphyria |
Erythropoietic porphyria |
Erythropoietic protoporphyria |
Galactosemia |
Hemochromatosis |
Lecithin cholesterol acyltransferase deficiency |
Mevalonic aciduria |
Pyroglutamic aciduria |
Red blood cells glycolysis defects |
Severe liver failure |
Transaldolase deficiency |
Wilson disease |
Wolman disease |
Bleeding tendency, hemorrhagic syndromes |
Gaucher disease |
Glycogenosis type Ia and Ib |
Inborn errors with severe liver failure |
Primitive disorders of homeostasis |
Severe thrombocytopenia |
Hemophagocytosis |
Gaucher disease |
Lysinuric protein intolerance |
Niemann-Pick disease |
Hyperleucocytosis (> 100.000) |
Leukocyte adhesion deficiency syndrome (CDG
IIc: GDP fucose transporter 1) |
Pancytopenia, thrombocytopenia, leukopenia |
Aspartylglucosaminuria |
CDG syndrome IIf (CMP sialic acid transporter) |
Gaucher type I and III |
Glycogenosis type Ib (neutropenia) |
Inborn errors of cobalamin metabolism |
Inborn errors of folate metabolism |
Johansson-Blizzard syndrome |
Lysinuric protein intolerance |
Organic acidurias (methylmalonic, propionic,
isovaleric) |
Other conditions with large splenomegaly |
Pearson syndrome |
Respiratory-chain disorders |
Schwachman syndrome |
Transaldolase |
Vacuolated lymphocytes |
Aspartylglycosaminuria |
Austin disease |
Ceroid lipofuscinosis |
I-cell disease (mucolipidosis type II) |
Landing disease (GM1) |
Mucopolysaccharidosis |
Niemann-Pick type Ia |
Pompe disease |
Sialidosis |
Wolman disease |
The Liver |
Cholestatic Jaundice |
α-1-antitrypsin deficiency |
Arginase deficiency |
Byler disease |
Carbohydrate-deficient glycoprotein syndrome |
Cerebrotendinous xanthomatosis |
Cholesterol synthesis defects (Smith-Lemli-Opitz) |
Citrin deficiency |
COG 7 deficiency |
Cystic fibrosis |
Galactosemia |
Inborn errors of bile acid metabolism |
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency |
Methylacyl-CoA racemase |
Mevalonic aciduria |
Niemann-Pick type C |
Peroxisomal disorders |
Transaldolase |
Tyrosinemia type I |
Cirrhosis |
Alpers progressive infantile poliodystrophy |
Alpha-1-antitrypsin deficiency |
Arginase deficiency |
Carbohydrate-deficient glycoprotein syndrome |
Cholesterol ester storage disease |
Cystic fibrosis |
Familial hepatic fibrosis with exudative enteropathy
(CDG Ib) |
Galactosemia |
Gaucher disease |
Glycogenosis type IV |
Hemochromatosis |
Hereditary fructose intolerance |
Hypermagnesemia with dystonia1 |
Long-chain 3-hydroxyl-acyl-CoA dehydrogenase
deficiency |
Niemann-Pick disease |
Peroxisomal disorders |
S-adenosine homocysteine hydrolase deficiency |
Transaldolase deficiency |
Tyrosinemia type I |
Wilson disease |
Wolman disease |
Liver failure (ascites, edema): see also Reye syndrome, part 10.1.9.3 |
Age at onset: congenital (hydrops fetalis) |
CDG syndrome |
Erythropoietic porphyria |
Galactosialidosis |
GM1 gangliosidosis (Landing) |
Mevalonic aciduria |
Mucopolysaccharidosis type VII |
Niemann-Pick A and C |
Sialidosis type II |
Transaldolase deficiency |
Age at onset: neonatal to early infancy |
Fatty acid oxidation disorders |
Fructose bisphosphatase deficiency |
Fructosemia |
Galactosemia |
Mevalonic aciduria |
Mitochondrial DNA depletion (DOGK) |
Neonatal hemochromatosis (prevented by immunoglobulin
to the pregnant mother) |
Respiratory-chain disorders |
Tyrosinemia type I (after 3 weeks) |
Age at onset: infancy |
Same defects as in neonatal period |
ACAD 9 |
Alpha-1-antitrypsin deficiency |
Carbohydrate-deficient glycoprotein syndrome |
Cholesterol ester storage disease |
Cystic fibrosis |
Familial hepatic fibrosis with exudative enteropathy
(CDG Ib) |
Ketogenesis defects |
Pyruvate carboxylase deficiency |
S-adenosyl homocystine hydrolase deficiency |
Urea cycle defects |
Wolman disease |
Age at onset: childhood to adolescence |
Wilson disease |
Immune System |
Inflammatory syndrome |
Hyper-IgD syndrome |
Mevalonate kinase deficiency |
Macrophage activating syndrome |
Gaucher disease |
Lysinuric protein intolerance |
Niemann-Pick disease |
Propionic acidemia |
Severe combined immune deficiency |
Adenosine deaminase deficiency |
Purine nucleoside phosphorylase |
Hereditary orotic aciduria |
Muscular System |
Exercise intolerance, myoglobinuria, cramps, muscle pain,
elevated CK |
Glycolytic defects (muscle “glycogenosis”) |
Phosphorylase deficiency (McArdle) |
Phosphofructokinase deficiency |
Phosphoglycerate kinase deficiency |
Phosphoglycerate mutase deficiency |
Lactate dehydrogenase deficiency |
Glucose-6-phosphate dehydrogenase deficiency |
Phosphorylase b kinase deficiency |
Fatty acid oxidation defects |
Carnitine palmitoyl transferase II |
VLCAD, LCHAD, translocase, trifunctional |
SCHAD (restricted to muscles), MCKAT |
Others undescribed (CPT I, SCAD) |
Miscellaneous |
Channelopathies (hyperkalemic paralysis) |
Idiopathic familial recurrent myoglobinuria |
Lipoamide dehydrogenase deficiency |
Maltase acid (adult) |
Myoadenylate deaminase deficiency |
Respiratory-chain disorders |
Myopathy (progressive) |
Adenylate deaminase deficiency |
Fatty acid oxidation disorders |
Glycogenosis type II (acid maltase deficiency) |
Glycogenosis type III |
Multisystemic triglyceride storage disease |
Respiratory-chain disorders (Kearns-Sayre and
others) |
Renal System |
Hemolytic uremic syndrome |
Inborn errors of cobalamin metabolism (Cbl C,
Cbl G) |
Nephrolithiasis/Nephrocalcinosis |
APRT deficiency (2,8-dihydroxyadenine) |
Cystinuria (cystine) |
Hereditary hyperparathyroidism (calcium) |
Hereditary renal hypouricemia (uric acid) |
Hyperoxaluria type I and II (oxalic) |
Lesch-Nyhan (uric acid) |
Molybdenum cofactor deficiency (xanthine) |
PRPP synthase superactivity (uric acid) |
Renal tubular acidosis type I |
Xanthine oxidase deficiency (xanthine) |
Familial juvenile hyperuricemic nephropathy
(uromodulin mutation) |
Nephrotic syndrome |
Respiratory-chain disorders |
Nephropathy (tubulointerstitial) |
Glycogenosis type I |
Methylmalonic aciduria |
Respiratory-chain disorders (pseudo Senior-Loken
syndrome) |
Polycystic kidneys |
Carbohydrate-deficient glycoprotein syndrome |
CPT II deficiency |
Glutaric aciduria type II |
Zellweger syndrome |
Tubulopathy |
Fanconi syndrome |
Fructose intolerance: galactosemia |
Respiratory-chain disorders (complex IV or mito
DNA deletion) |
Tyrosinemia type I |
Fanconi-Bickel syndrome: Glut II mutations |
Lowe syndrome (OCRL1 X-linked mutations) |
Cystinosis |
Renal tubular acidosis |
Pyruvate carboxylase deficiency |
Methylmalonic aciduria |
Glycogenosis type I |
Carnitine palmitoyl transferase I deficiency |
Dent disease (CLCN5 mutations) |
Urine (abnormal color) |
Alkaptonuria (black) |
Indicanuria (blue) |
Myoglobinuria (red) |
Porphyria (red) |
Urine (abnormal odor) |
Dimethylglycine dehydrogenase (fish) |
3-CH3-crotonylglycinuria (cat) |
Glutaric aciduria type II (sweaty feet) |
Isovaleric acidemia (sweaty feet) |
MSUD (maple syrup) |
Phenylketonuria (musty odor) |
Trimethylaminuria (fish) |
Tyrosinemia type I (boiled cabbage) |
Neurological and Psychiatric signs |
Calcifications in the brain |
Deafness (sensorineural) |
Detectable in neonatal to early infancy |
Zellweger and variants |
Rhizomelic chondrodysplasia punctata |
Acyl-CoA oxidase deficiency |
Encephalopathy with hyperkinurininuria |
Detectable in late infancy to childhood |
Infantile Refsum disease (pseudo Usher syndrome) |
PRPP synthetase overactivity |
Mucopolysaccharidosis type I, II, and IV |
Mannosidosis (alpha) |
Mucolipidosis type II (I cell disease) |
Biotinidase deficiency (biotin responsive; untreated
or treated late) |
Megaloblastic anemia, diabetes, and deafness
(B1-responsive) |
Wolfram syndrome |
Neutral lipid storage disorder |
Mitochondrial encephalomyopathy |
Mitochondrial encephalopathy lactic acidosis
strokelike episodes (MELAS), myoclonic epilepsy ragged red fibers
(MERFF), Kearns-Sayre syndrome |
Detectable in late childhood to adolescence |
Beta-mannosidosis |
Refsum disease (adult form) |
Usher syndrome type II |
MERFF, Kearns-Sayre syndrome |
Epilepsy |
Leigh syndrome |
Biotinidase deficiency |
EPEMA syndrome |
Fumarase deficiency |
MAMEL syndrome |
Pyruvate carboxylase deficiency |
Pyruvate dehydrogenase deficiency |
Respiratory-chain disorders |
Sulfite oxidase deficiency |
3-methylglutaconic aciduria |
Leukodystrophy |
Macrocephaly |
Alexander |
Canavan (acetylaspartaturia) |
Gangliosidosis GM2 (Sandhoff, Tay-Sachs) |
Glutaric aciduria type I |
Krabbe (infantile form) |
L-2-hydroglutaric aciduria |
Respiratory-chain disorders |
Vacuolizing encephalopathy |
Microcephaly |
Congenital |
Infant born to untreated PKU mother |
Sulfite oxidase deficiency |
3P-glycerate phosphate dehydrogenase (improved
by serine) |
Acquired |
Many untreated disorders in which microcephaly
is a symptom of a nonspecific cerebral atrophy |
Movement disorders |
Neuroimaging abnormalities at CT scan, MRI, 1H-MRS |
Calcifications on CT-scan |
Biopterin metabolism defects |
Cockayne syndrome |
Congenital lactic acidemias |
Folic acid metabolism defects |
GM2 gangliosidosis |
Kearns-Sayre |
Leigh syndrome |
MELAS syndrome |
Respiratory-chain disorders |
3-hydroxyisobutyric aciduria |
White matter hyperintensity |
With increased head circumference |
Alexander (anterior) |
Canavan |
Glutaric aciduria type I (bitemporal atrophy) |
L2-hydroxyglutaric |
Mucopolysaccharidosis (with vacuoles) |
Vacuolizing leukoencephalopathy |
With normal head circumference |
Predominantly periventricular white matter |
Cerebrotendinous xanthomatosis* |
Homocysteine remethylation defects* |
Glutaric aciduria type I* |
Kearns-Sayre |
L2-hydroxyglutaric |
Menkes |
Metachromatic leukodystrophy* |
Mitochondrial cytopathy |
MNGIE (with supratentorial cortical atrophy) |
Pelizaeus-Merzbacher (myelination arrest) |
Peroxisomal biogenesis defects,* PEX-7 |
PKU (untreated, reversible)* |
Polyglucosan body disease* |
Ribose-5-phosphate isomerase* (arabitol,
ribitol peaks) |
X-ALD (posterior) |
3-methylglutaryl CoA lyase* |
Predominantly pyramidal tracts |
Adrenomyeloneuropathy* |
Cerebrotendinous xanthomatosis* |
Krabbe disease* |
Mitochondrial cytopathies* |
Affecting U fibers |
Mitochondrial cytopathies* |
Polyglucosan body disease* |
Ribose-5-phosphate isomerase* (arabitol,
ribitol peaks) |
2-hydroxyglutaric aciduria* |
Basal ganglia/brain stem hyperintensities |
Biotin-responsive basal ganglia disease12 (bilateral
necrosis of caudate nucleus and putamen) |
Cerebrotendinous xanthomatosis* |
GM1 Gangliosidosis* |
Hypoceruloplasminemia* (diffuse hypointensity) |
Infantile bilateral striatal necrosis |
Leigh syndrome (putamen, caudate nuclei) |
L2-hydroxyglutaric aciduria |
Methylmalonic aciduria (pallidum) |
Mitochondrial cytopathies* |
Neuroferritinopathy* (pallidum) |
PKAN* (Hallervorden-Spatz, HARP syndrome:
hypointensity; tiger eye) |
Pyruvate dehydrogenase deficiency* |
Wernicke encephalopathy* (thalami,
brain stem) |
Wilson disease* |
Dentate nuclei of the cerebellum hyperintensities |
Cerebrotendinous xanthomatosis* |
L2-hydroxyglutaric |
Mitochondrial encephalopathy* |
Polyglucosan body disease* |
Semialdehyde succinate dehydrogenase* |
Wilson disease* |
Gyration abnormalities |
CEDNIK (snare protein mutation)17 |
O-glycosylation disorders: muscle eye brain
disease (POMGnT), Walker-Warburg syndrome (POMT1), Fukuyama (fukutin) |
Peroxisomal disorders (Zellweger and others) |
Corpus callosum agenesis |
With gyration abnormalities |
ACTH deficiency |
Complex II mitochondrial cytopathies (with leukodystrophy) |
Nonketotic hyperglycinemia |
PDH (with basal ganglia abnormalities) |
3-hydroxyisobutyric aciduria |
Posterior fossa (and olivo-ponto-cerebellar) |
Hypoplasia |
CDG syndrome |
Congenital muscular dystrophies |
Joubert syndrome |
Mitochondrial cytopathies |
Peroxisomal disorders |
Progressive atrophy |
Ceroid lipofuscinosis* |
GM1 gangliosidosis (Landing) |
L-2-hydroxyglutaric aciduria |
Mevalonic aciduria (mevalonate kinase) |
Neuroaxonal dystrophy (infantile) |
Schindler |
Smith-Lemli-Opitz |
Succinyl semialdehyde dehydrogenase deficiency |
3-methylglutaconic aciduria |
Stroke and strokelike episodes |
CDG syndrome |
Homocystinurias* |
MELAS syndrome* |
Fabry disease |
Polyneuropathy: EMG, NCV findings |
Acute (recurrent attacks) |
Porphyrias* |
Tyrosinemia type I |
Chronic |
Predominantly demyelination (low NCV) |
X-ALD (childhood to adulthood): leukodystrophy |
AMN (adulthood) |
Austin disease |
β-mannosidosis |
Farber lipogranulomatosis |
Homocysteine remethylation defects (MTHFR, CblC) |
Krabbe (leukodystrophy) |
Metachromatic leukodystrophy (leukodystrophy) |
MNGIE syndrome (leukodystrophy) |
Refsum disease (late childhood to adulthood) |
Tangier disease |
Predominantly axonal (normal NCV) |
Presenting or preponderant |
Abetalipoproteinemia (childhood) |
α-methyl-acyl-CoA racemase
(adolescence to adulthood) |
CDG type I (childhood) |
GM2 gangliosidosis* |
LCHAD, trifunctional (childhood to adolescence) |
Peroxisomal biogenesis defects (late childhood
to adult) |
Polyglucosan body disease* (leukodystrophy) |
Pyruvate dehydrogenase (childhood to adulthood) |
Vitamin E malabsorption (tocopherol carrier) |
Accompanying symptom |
Cerebrotendinous xanthomatosis* (leukodystrophy) |
Neuroaxonal dystrophy, Schindler (early childhood;
leukodystrophy) |
Ornithine amino transferase (late complications) |
P5C synthase (late childhood) |
Porphyria* |
Pyroglutamic aciduria (late complication) |
Respiratory chain (early childhood to adolescence) |
Serine deficiency syndrome (adolescence) |
Triose phosphate isomerase |
Affecting small sensitive fibers and the autonomic
nervous system |
Fabry disease* (presenting sign) |
GM2 gangliosidosis* |
Porphyria* |
Tangier disease* |
Affecting anterior horn |
GM2 gangliosidosis, Krabbe disease |
Homocysteine remethylation defects (ClbC) |
Nonketotic hyperglycinemia |
Pantotenate kinase (Hallervorden-Spatz; basal
ganglia) |
Polyglucosan body disease* |
Psychiatric signs: schizophrenia, autistic behavior, agitation,
aggressiveness, hysteria |
Pyramidal syndrome, spasticity, spastic paraplegia; see 10.1.12 |
Self mutilation, auto-aggression |
Lesch-Nyhan syndrome |
Phenylketonuria (untreated) |
Tyrosinemia type I (crisis) |
3-methylglutaconic aciduria |
The Eyes |
Cataracts |
Detectable at birth (congenital) |
Cockayne syndrome |
Lowe syndrome (OCRL1 X-linked mutation) |
Peroxisomal biogenesis defects (Zellweger and
variants) |
Phosphoglycerate dehydrogenase deficiency |
Rhizomelic chondrodysplasia punctata |
Sorbitol dehydrogenase deficiency |
Detectable in the newborn period (first week
to first months) |
Galactosemias |
Marginal maternal galactokinase deficiency |
Peripheral epimerase deficiency (homozygotes
and heterozygotes) |
Detectable in infancy (first months to first
years) |
Alpha-mannosidosis |
Galactitol or sorbitol accumulation of unknown
origin |
Galactokinase deficiency |
Hypoglycemia (various origins) |
P5C synthase deficiency |
Respiratory chain disorders |
Sialidosis |
Detectable in childhood (1 to 15 years) |
Diabetes mellitus |
Dominant cataract with high serum ferritin |
Hypoparathyroidism |
Lysinuric protein intolerance |
Mevalonic aciduria |
Neutral lipid storage disorders (unknown cause) |
Pseudo-hypoparathyroidism |
Sjögren-Larsson syndrome |
Wilson disease |
Detectable in adulthood (> 15 years): |
Carriers for Lowe syndrome |
Cerebrotendinous xanthomatosis |
Fabry disease |
Glucose-6-phosphate dehydrogenase deficiency |
Heterozygotes for GUT and galactokinase |
Homocystinurias |
Lactose malabsorbers |
Mevalonate kinase |
Mitochondrial cytopathies |
Ornithine aminotransferase deficiency |
PEX 7 |
Refsum disease |
Steinert dystrophy (cataract can be presenting
sign) |
Tangier disease |
Cherry-red spot |
Cytochrome C oxidase deficiency |
Galactosialidosis (neuraminidase deficiency) |
Gangliosidosis GM1 (Landing) |
Gangliosidosis GM2 (Sandhoff, Tay-Sachs) |
Nephrosialidosis |
Niemann-Pick type A, C, and D |
Sialidosis type I |
Corneal opacities (clouding) |
Visible in early infancy (3 to 12 months) |
Tyrosinemia type II (presenting sign) |
Cystinosis (presenting sign) |
Hurler, Sheie (MPS I) |
I-cell disease (mucolipidosis type II) |
Maroteaux-Lamy (MPS VI) |
Steroid sulfatase deficiency |
Visible in late infancy to early childhood (1
to 6 years) |
Mucolipidosis type IV (presenting sign) |
Alpha-mannosidosis (late-onset form) |
Lecithin cholesterol acyltransferase deficiency |
Morquio (MPS IV) |
Pyroglutamic aciduria (presenting sign) |
Tangier disease |
Visible in late childhood, adolescence to adulthood |
Fabry disease (X-linked) |
Galactosialidosis (juvenile form) |
Wilson disease (green Kaiser Fleischer ring) |
Ectopia lentis (dislocation of the lens) |
Classical homocystinuria (downward dislocation) |
Sulfite oxidase deficiency |
Marfan syndrome (upward dislocation) |
Keratitis, corneal opacities |
Tyrosinemia type II |
Fabry disease (X-linked) |
Microcornea |
Ehlers-Danlos type IV |
Nystagmus |
With retinitis pigmentosa |
Abetalipoproteinemia* |
Ceroid lipofuscinosis (CLN1, CLN2, CLN3,* CLN4*) |
LCHAD* |
Mitochondrial cytopathies (Kearns-Sayre,* etc) |
Peroxisomal defects (infantile to childhood) |
Sjögren-Larsson (fatty acid alcohol
oxidoreductase) |
All causes of severe retinitis pigmentosa |
With optic atrophy |
All causes of optic atrophy in adulthood* |
Canavan disease (early sign) |
Ceroid lipofuscinosis (CLN3,* CLN4*) |
Krabbe disease (infantile) |
Leber due to mitochondrial DNA deletions* |
Leigh syndrome (all causes) |
Metachromatic leukodystrophy* |
Mitochondrial cytopathies* |
Neuroaxonal dystrophy: Schindler (infantile) |
Pelizaeus-Merzbacher (presenting sign early
in infancy) |
Peroxisomal biogenesis defects* |
Pyruvate dehydrogenase deficiency* |
Ribose-5-phosphate isomerase* |
Sulfite oxidase (infantile) |
X-ALD* |
3-methylglutaconic aciduria (Costeff syndrome) |
With corneal opacities, cataract |
Fabry disease* |
Homocystinurias* |
Lowe syndrome (infancy) |
Mucopolysaccharidosis (childhood) |
Wilson disease* |
Ophthalmoplegia, ptosis, eye movements, strabismus |
Neonatal to early infancy |
Aromatic amino acid decarboxylase (oculogyric
crises) |
CDG Ia (with congenital strabismus) |
Pyridox(am)ine-5-phosphate oxidase |
Tyrosine hydroxylase |
Infancy to childhood |
Ataxia telangiectasia (ocular contraversion,
telangiectasia) |
Gaucher type III (horizontal supranuclear paralysis) |
Leigh syndrome (acute attacks of abnormal movements) |
Niemann-Pick C and D (vertical supranuclear
paralysis) |
Pyruvate dehydrogenase (acute attacks of abnormal
movements) |
Respiratory chain (acute attacks of abnormal
movements) |
Adulthood |
Glutaric aciduria type I |
GM2 gangliosidosis (abnormal eye movements) |
Mitochondrial cytopathies: Kearns-Sayre (abnormal
movements) |
Niemann-Pick C, Gaucher III |
Nonketotic hyperglycinemia |
Pyruvate dehydrogenase (abnormal movements) |
Wilson disease |
Ptosis; see Ophthalmoplegia above |
Retinitis pigmentosa |
Aceruloplasminemia* |
Carbohydrate deficient glycoprotein syndrome |
Ceroid lipofuscinosis: CLN1, CLN2, CLN3 |
Cobalamin metabolism defects: CblC* |
Gyrate atrophy with ornithine aminotransferase
deficiency |
Inborn errors of lipid metabolism |
Abetalipoproteinemia |
Sjögren-Larsson syndrome |
Vitamin E malabsorption (tocopherol carrier) |
3-hydroxyacyl CoA dehydrogenase |
Panthothenate kinase* (Hallervorden-Spatz,
Harp syndrome) |
Peroxisomal biogenesis defects |
α-methyl-CoA racemase* |
Classical Refsum disease* |
Isolated fatty acid oxidation defects |
Peroxisomal biogenesis defects (Zellweger, NALD,
Refsum and variants) |
Respiratory-chain disorders |
Kearns-Sayre syndrome* |
NARP |
Other mitochondrial DNA deletions |
Strabismus; see Ophthalmoplegia above |
Skeletal System |
Osteopenia |
Cerebrotendinous xanthomatosis |
CDG syndrome |
Glycogenosis type I |
Homocystinuria |
I-cell disease (mucolipidosis type II) |
Infantile Refsum disease |
Lysinuric protein intolerance |
All organic acidurias (chronic forms) |
Punctate epiphyseal calcifications |
Beta-glucuronidase deficiency |
Chondrodysplasia punctata rhizomelic type |
Conradi-Hunermann syndrome |
Familial resistance to thyroid hormone |
Peroxisomal disorders (Zellweger and variants) |
Warfarin embryopathy |
Exostosis (hereditary multiple) |
O-glycosylation defects (EXT1-EXT2) |
Respiratory System |
Hyperventilation attacks |
Hyperammonemias |
Joubert syndrome |
Leigh syndrome (idiopathic or due to various
inborn errors) |
Metabolic acidosis |
Rett syndrome (only girls) |
Pneumopathy (interstitial) |
Gaucher disease |
Lysinuric protein intolerance |
Niemann-Pick type B |
Stridor |
Biotinidase |
Hypocalcemia |
Hypomagnesemia |
Multiple acyl-CoA dehydrogenase deficiency (riboflavin
responsive) |
Pelizaeus-Merzbacher |
Pulmonary hypertension |
Glycogenosis type I |
Nonketotic hyperglycinemia |
Rheumatology |
Arthritis, joint contractures, bone necrosis |
Alkaptonuria |
Familial gout |
Farber disease |
Gaucher type I |
Homocystinuria |
I-cell disease, mucolipidosis type III |
Lesch-Nyhan syndrome |
Mevalonic aciduria (recurrent crisis of arthralgia) |
Mucopolysaccharidosis type I S |
PRPP synthetase, HGPRT |
Uromoduline mutation (familial hyperuricemic
nephropathy) |
Bone crisis |
With bone changes (rickets) |
Calciferol metabolism deficiency |
Hereditary hypophosphatemic rickets |
With hemolytic crises and abdominal pain |
Porphyrias |
Sickle cell anemia |
Tyrosinemia type I |
With progressive neurological signs |
Gaucher type III |
Krabbe disease |
Metachromatic leukodystrophy |
Apparently isolated (presenting symptom) |
Fabry disease |
Gaucher type I |
Mouth and Tongue |
Glossitis, stomatitis |
Cbl F |
Folate malabsorption |
Intrinsic factor deficiency |
Transcobalamin II |
Macroglossia |
Complex IV deficiency |
Mucopolysaccharidoses |
Pompe disease |
Vascular System |
Raynaud Syndrome |
Fabry disease |
Thromboembolic accidents: strokelike episodes |
CDG syndrome |
Ehlers-Danlos type IV |
Fabry disease |
Homocystinuria (all types) |
Menkes disease |
Organic acidurias (methylmalonic, propionic) |
Respiratory-chain disorders (MELAS and others) |
Urea cycle disorders (OTC deficiency) |