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Features
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Answer
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TIAs/strokes due to bilateral cerebral arterial disease, particularly in the circle of Willis [sporadic]
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moyamoya
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Neuropsychiatric + liver disease presentation due to copper build up [AR, ATP7B gene]
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Wilson
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cafe-au-lait spots, peripheral nerve sheath tumours, optic glioma, renal artery stenosis [AD]
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Neurofibromatosis 1
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vestibular shwannomas [AD]
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Neurofibromatosis 2
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Sphingolipidosis. Neurological symptoms inc cerebellar and basal ganglia dysfunction, gelastic cataplexy, hepatosplenomegaly [AR]
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Niemann-Pick
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non-syndromic genetic HL [AR, connexin 26 gap junction protein mutations]
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GJB2
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exercise-induced muscle fatigue and cramps, muscle hypertrophy, rhabdomyalysis, NO hepatomegaly or hypoglycaemia [AR, muscle glycogen phosphorylase deficiency]
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GSD V (McArdle's)
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Arm/hand abnormalities (e.g. forearm deformities) + CHD (e.g. ASD) [AD, TBX5 gene]
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Holt-Oram
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asymptomatic in children, blue skin/scleral pigmentation, dark urine, later arthritis, vascular heart disease, renal stones, hearing loss [AR]
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Alkaptonuria
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spastic paraplegia and liver dysfunction, raised ornithine, homocitrulline and urinary orotic acid [AR]
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Ornithine transporter deficiency (Hyperornithinaemia hyperammonaemia homocitrullinaemia)
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Progressive neurodegenerative disorder, onset at 2-4 years. Seizures esp myoclonic, visual problems, motor decline.
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Late infantile ceroid lipofuscinosis
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Dysmorphic features, high pitched cry, poor growth, developmental delay [5p deletion]
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Cri-du-Chat
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conductive hearing loss in up to 80% [Sporadic]
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Down
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coarse facial features, skeletal abnormalities, joint stiffness, abdominal hernias, developmental delay, cardiac abnormalities, cataracts [AR, alpha-L-iduronidase deficiency]
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MPS II (Hurler)
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retinal dystrophy + SNHL [AR]
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Usher
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thyroid dysmorphogenesis + congenital SNHL (high freqhency) [AR, SCL26A4 (a chloride/iodide transporter) mutations]
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Pendred
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hepatomegaly and cirrhosis, myopathy, dilated cardiomyopathy [AR, glycogen branching enzyme deficiency]
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GSD IV (Andersen's)
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Neonatal hypoglycaemia, macroglossia, hemihypertrophy, anterior abdominal wall defects, embryonal tumours. Frequent feeds + diazoxide to prevent hypos [Sporadic]
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Beckwith-Widemann
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Gangliosidosis. Progressive neurological condition. Motor regression, siezures, hearing loss. Retinal red spot. More common in Ashkenazi Jewish, Old Order Amish, Quebec French Canadian communities [AR, HEXA mutation]
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Tay-Sachs
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tumour suppressor gene mutation -> visceral cysts + tumours. Retinal, cerebellar, spinal haemangioblastomas, renal cell carcinoma, phaeochromocytoma, pancreatic tumours [AD]
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Von Hippel-Lindau
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Fanconi syndrome (proximal RTA + hypophosphataemia + glucosuria + proteinuria/aminoaciduria), faltering growth, hypophosphataemic rickets, polyuria/polydipsia, photophobia due to corneal accumulation, diabetes, thyroid, and neurological problems [AR, CTNS mutation]
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Cystinosis
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acidosis with ketosis, raised lactate, hyperammonaemia, neutropenia, part of blood spot [AR]
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Isovaleric acidaemia
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hypoglycaemia, hepatomegaly, faltering growth, hyperlipidaemia, myopathy [AR, glycogen debranching enzyme deficiency]
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GSD III (Cori's)
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initially asymptomatic with acute decompensation resulting in encephalopathy, classically bilateral subdurals; part of blood spot [AR]
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Glutaric aciduria type 1
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Sphingolipidosis. Pancytopenia, hepatosplenomegaly, joint and bone pain, neurological symptoms, osteoporosis [AR]
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Gaucher's
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cardiomyopathy, muscle weakness, liver disease; very low total and free carnitine, no dicarboxylic aciduria [AR]
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Carnitine transporter defect
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neonatal hyperammonaemia, raised glutamine, low citrulline, raised urinary orotic acid [XR]
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OTC deficiency
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Craniosynastosis + syndactyly + hypertelorism, maxillary hypoplasia + cleft palate [AD]
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Apert
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liver disease, renal tubular acidosis; high total/free carnitine and low C16, 18, 18:1, no dicarboxylic aciduria [AR]
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Carnitine palmitoyltransferase I deficiency (CPT I)
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Pancytopenia + pancreatic insufficiency + skeletal abnormalities + hepatomegaly [AR, SBDS mutation - ribosome abnormality]
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Shwachman-Diamond
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coarse facial features, skeletal abnormalities, joint stiffness, abdominal hernias, developmental delay, cardiac abnormalities [XR, iduronate-2-sulfatase deficiency]
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MPS I (Hunter)
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severe hypoglycaemia, hepatomegaly, faltering growth, hyperlipidaemia, lactic acidosis, hyperuricaemia [AR, glucose-6-phosphatase deficiency]
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GSD I (von Gierke's)
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nephritis + SNHL (high freqnecy) [XL, AD, AR]
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Alport
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port-wine stain, LD, seizures, hemiparesis, glaucoma [Sporadic]
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Sturge-Weber
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neonatal hyperammonaemia, raised glutamine, low citrulline, normal urinary orotic acid, can be managed with carbaglumic acid [AR]
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N-acetylglutamate synthase deficiency
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Developmental regression, acquired microcephaly, repetitive hand movements. [XD, MECP2 mutation]
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Rett
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acidosis with ketosis, raised lactate, hyperammonaemia, neutropenia, extrapyramidal signs, cardiomyopaty, x1 raised organic acid in urine [AR]
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Propionic acidaemia
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spastic paraplegia and developmental delay, raised arginine and urinary orotic acid, can be treated with degzilarginase artificial enzyme [AR]
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Arginase 1 deficiency (Arginaemia)
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cardiomyopathy, liver disease, hepatomegaly, sudden death in infancy, late-onset rhabdomyalisis [AR]
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VLCADD
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posterior fossa malformations, haemangiomas, arterial lesions, cardiac abmormalities e.g. coarctation of the aorta, eye abnormalities, sternal cleft
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PHACES
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Thrombocytoenia (-> haemorrhagic complications in the newborn) + absent radii + facial dysmorphism + lower limb anomalies + cow's milk intolerance [AR, RBM8A]
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Thrombocytopenia absent radii (TAR)
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pigmentary anomalies of hair/skin/eyes + HL [AD]
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Waardenburg
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Pulmonary hypoplasia + low set ears, flat nasal bridge + contractures + clubbed feet [various causes of oligohydramnios]
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Potter sequence
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Copper metabolism. Progressive neurodegeneration and seizures. Rosy cheeks and friable hair. Low serum copper [XR]
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Menke's
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fair skin, microcephaly and progressive cognitive impairment, part of blood spot [AR]
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Phenylketonuria
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Autonomic dysfunction (poor suck/swallow, temperature regulation, vomiting) + peripheral sensory neuropathy + decreased taste due to absence of fungiform papillae + absence of tears [AR]
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Riley-Day
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Pancytopenia + short stature + microcephaly + cafe-au-lait sots + upper limb abnormalities + renal anomalies (e.g. horseshoe kidney) [AR, FA/BRCA pathway mutations]
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Fanconi's anaemia
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hepatic and renal failure [AR]
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Tyrosinaemia
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severe cardiomyopathy, arrythmias, liver diseasae; low total carnitine, may have dicarboxylic aciduria [AR]
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Carnitine translocase deficiency
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Reye-like progressive crisis after 8-16 hours of fasting; hypoketotic hypoglycaemia; dicarboxylic aciduria [AR]
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MCADD
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lysosomal sotrage defect resulting in AA accumulation, Fanconi syndrome (proximal RTA + hypophosphataemia + glucosuria + proteinuria/aminoaciduria), faltering growth, hypophosphataemic rickets, polyuria/polydipsia, photophobia due to corneal accumulation, diabetes, thyroid, and neurological problems [AR, CTNS mutation]
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Cystinosis
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ash leaf macules, Shagreen patches, LD, epilepsy inc infantile spasms, cardiac rhabdomyomas, renal angiomyolipomas [AD]
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Tuberous sclerosis
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Eczema + immunodeficiency + thrombocytopenia [XR]
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Wiskott-Aldrich
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AA reabsorption defect: renal stones (hexagonal), diagnosed with sodium cyanide nitroprusside test and managed with alkalinisation of urine and penicillamine chellation [AR]
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Cystinuria
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Anaemia + short stature + thumb and craniofacial abnormalities - presents in infancy [AD or sporadic, ribosomal genes]
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Diamond-Blackfan
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acidosis with ketosis, raised lactate, hyperammonaemia, neutropenia, extrapyramidal signs, cardiomyopaty, renal failure, x2 raised organic acids in urine [AR]
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Methylmalonic acidaemia
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long QT syndrome + congenital SNHL [AD, KCNQ1/KCNE1 (potassium channels) mutations]
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Jervell-Lange-Nielsen
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coloboma, heart defects, choanal atresia, developmental delay, genital hyoplasia, absent semicircular canals + VIIIth nerve hypoplasia [AD]
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CHARGE
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neonatal hyperammonaemia, raised citrulline, raised urinary orotic acid [AR]
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ASS deficiency (Citrullinaemia I)
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Hemihypertrophy of the bone or soft tissues associated with an overlying port-wine stain. If AVM present then *-Weber syndrome
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Klippel-Trenaunay
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neonatal hyperammonaemia, raised citrulline, raised urinary orotic acid and ASA [AR]
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ASL deficiency (Arginosuccinaemic aciduria)
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Neuropathic pain esp in the limbs + angiokeratomas + corneal opacities + early strokes + CKD + hypertrophic cardiomyopathy [XR]
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Fabry
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Congenital nephropathy + Wilm's tumour + intersex
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Denys-Drash
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Cerebellar dysfunction (ataxia from age 1-2, progressive deterioration around 8-12) + immunodeficiency (humoral) + later telangectasia [AR]
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Ataxia telangectasia
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marfanoid body habitus, eye problems inc lens dislocation, VTE/strokes, learning difficulties, part of blood spot except for a B6-responsive subtype [AR]
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Homocystinuria
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encephalopathy, seizures, cerebral oedema, acidosis with ketosis, raised branch chain amino acids, part of blood spot [AR]
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Maple Syrup Urine Disease
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coarse facial features, macroglossia, hypotonia, HOCM [AR, alpha-glucosidase deficiency]
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GSD II (Pompe)
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Developmental abnormality of midline brain structures. Optic nerve hypoplasia (-> congenital blindness), hypopituitarism, absent septum pellucidum. Roving eye movements in infant (rotatory nystagmus).
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Septo-optic dysplasia
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Dysarthria, abnormal movements, anaemia. Malabsorption, failure to thrive, visual problems including retinitis pigmentosa. Acanthocytes on blood film [AR]
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Abetalipoproteinaemia
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cariomyopathy, liver disease, hypotonia, neuropathy, retinopathy, late-onset rhabdomyalisis; associated with maternal steatosis or HELLP syndrome; dicarboxyclic aciduria [AR]
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LCADD
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Hypotonia, lethargy, coma, seizures, choreas [AR]
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Non-ketotic hyperglycinaemia
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Oculocerebrorenal dystrophy. Congenital cataracts, glaucoma, bupthalmos. Hypotonia, hyporeflexia. Progressive intellectual disability. Fanconi syndrome. Rickets and pathological fractures [XR]
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Lowe
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cardiomyopathy, liver disease; low total carnitine and no/non-specific dicarboxylic aciduria [AR]
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Carnitine palmitoyltransferase II deficiency (CPT II)
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