Paediatric syndromes I: neurological and metabolic

cafe-au-lait spots, peripheral nerve sheath tumours, optic glioma, renal artery stenosis [AD]

vestibular shwannomas [AD]

port-wine stain, LD, seizures, hemiparesis, glaucoma [Sporadic]

ash leaf macules, Shagreen patches, LD, epilepsy inc infantile spasms, cardiac rhabdomyomas, renal angiomyolipomas [AD]

pigmentary anomalies of hair/skin/eyes + HL [AD]

coloboma, heart defects, choanal atresia, developmental delay, genital hyoplasia, absent semicircular canals + VIIIth nerve hypoplasia [AD]

nephritis + SNHL (high freqnecy) [XL, AD, AR]

retinal dystrophy + SNHL

thyroid dysmorphogenesis + congenital SNHL (high freqhency) [AR, SCL26A4 (a chloride/iodide transporter) mutations]

long QT syndrome + congenital SNHL [AD, KCNQ1/KCNE1 (potassium channels) mutations]

conductive hearing loss in up to 80% [Sporadic]

non-syndromic genetic HL [AR, connexin 26 gap junction protein mutations]

severe cardiomyopathy, arrythmias, liver diseasae; low total carnitine, may have dicarboxylic aciduria [AR]

cardiomyopathy, muscle weakness, liver disease; very low total and free carnitine, no dicarboxylic aciduria [AR]

liver disease, renal tubular acidosis; high total/free carnitine and low C16, 18, 18:1, no dicarboxylic aciduria [AR]

cardiomyopathy, liver disease; low total carnitine and no/non-specific dicarboxylic aciduria [AR]

cardiomyopathy, liver disease, hepatomegaly, sudden death in infancy, late-onset rhabdomyalisis [AR]

cariomyopathy, liver disease, hypotonia, neuropathy, retinopathy, late-onset rhabdomyalisis; associated with maternal steatosis or HELLP syndrome; dicarboxyclic aciduria [AR]

Reye-like progressive crisis after 8-16 hours of fasting; hypoketotic hypoglycaemia; dicarboxylic aciduria [AR]

severe hypoglycaemia, hepatomegaly, faltering growth, hyperlipidaemia, lactic acidosis, hyperuricaemia [AR, glucose-6-phosphatase deficiency]

coarse facial features, macroglossia, hypotonia, HOCM [AR, alpha-glucosidase deficiency]

hypoglycaemia, hepatomegaly, faltering growth, hyperlipidaemia, myopathy [AR, glycogen debranching enzyme deficiency]

hepatomegaly and cirrhosis, myopathy, dilated cardiomyopathy [AR, glycogen branching enzyme deficiency]

exercise-induced muscle fatigue and cramps, muscle hypertrophy, rhabdomyalysis, NO hepatomegaly or hypoglycaemia [AR, muscle glycogen phosphorylase deficiency]

neonatal hyperammonaemia, raised glutamine, low citrulline, normal urinary orotic acid, can be managed with carbaglumic acid [AR]

neonatal hyperammonaemia, raised glutamine, low citrulline, raised urinary orotic acid [XR]

neonatal hyperammonaemia, raised citrulline, raised urinary orotic acid [AR]

neonatal hyperammonaemia, raised citrulline, raised urinary orotic acid and ASA [AR]

spastic paraplegia and developmental delay, raised arginine and urinary orotic acid, can be treated with degzilarginase artificial enzyme [AR]

spastic paraplegia and liver dysfunction, raised ornithine, homocitrulline and urinary orotic acid [AR]

encephalopathy, seizures, cerebral oedema, acidosis with ketosis, raised branch chain amino acids, part of blood spot [AR]

acidosis with ketosis, raised lactate, hyperammonaemia, neutropenia, part of blood spot [AR]

acidosis with ketosis, raised lactate, hyperammonaemia, neutropenia, extrapyramidal signs, cardiomyopaty, x1 raised organic acid in urine [AR]

acidosis with ketosis, raised lactate, hyperammonaemia, neutropenia, extrapyramidal signs, cardiomyopaty, renal failure, x2 raised organic acids in urine [AR]

initially asymptomatic with acute decompensation resulting in encephalopathy, classically bilateral subdurals; part of blood spot [AR]

fair skin, microcephaly and progressive cognitive impairment, part of blood spot [AR]

hepatic and renal failure [AR]

asymptomatic in children, blue skin/scleral pigmentation, dark urine, later arthritis, vascular heart disease, renal stones, hearing loss [AR]

Hypotonia, lethargy, coma, seizures, choreas [AR]

marfanoid body habitus, eye problems inc lens dislocation, VTE/strokes, learning difficulties, part of blood spot except for a B6-responsive subtype [AR]

AA reabsorption defect: renal stones (hexagonal), diagnosed with sodium cyanide nitroprusside test and managed with alkalinisation of urine and penicillamine chellation [AR]

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]

coarse facial features, skeletal abnormalities, joint stiffness, abdominal hernias, developmental delay, cardiac abnormalities [XR, iduronate-2-sulfatase deficiency]

coarse facial features, skeletal abnormalities, joint stiffness, abdominal hernias, developmental delay, cardiac abnormalities, cataracts [AR, alpha-L-iduronidase deficiency]

coarse facial features, macroglossia, hypotonia, HOCM [AR, alpha-glucosidase deficiency]

Sphingolipidosis. Pancytopenia, hepatosplenomegaly, joint and bone pain, neurological symptoms, osteoporosis [AR]

Sphingolipidosis. Neurological symptoms inc cerebellar and basal ganglia dysfunction, gelastic cataplexy, hepatosplenomegaly [AR]

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]

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]

Neonatal hypoglycaemia, macroglossia, hemihypertrophy, anterior abdominal wall defects, embryonal tumours. Frequent feeds + diazoxide to prevent hypos [Sporadic]

Developmental abnormality of midline brain structures. Optic nerve hypoplasia (-> congenital blindness), hypopituitarism, absent septum pellucidum. Roving eye movements in infant (rotatory nystagmus).

tumour suppressor gene mutation -> visceral cysts + tumours. Retinal, cerebellar, spinal haemangioblastomas, renal cell carcinoma, phaeochromocytoma, pancreatic tumours [AD]

Dysarthria, abnormal movements, anaemia. Malabsorption, failure to thrive, visual problems including retinitis pigmentosa. Acanthocytes on blood film [AR]

Oculocerebrorenal dystrophy. Congenital cataracts, glaucoma, bupthalmos. Hypotonia, hyporeflexia. Progressive intellectual disability. Fanconi syndrome. Rickets and pathological fractures [XR]

posterior fossa malformations, haemangiomas, arterial lesions, cardiac abmormalities e.g. coarctation of the aorta, eye abnormalities, sternal cleft

Progressive neurodegenerative disorder, onset at 2-4 years. Seizures esp myoclonic, visual problems, motor decline.

Developmental regression, acquired microcephaly, repetitive hand movements. [XD, MECP2 mutation]

Copper metabolism. Progressive neurodegeneration and seizures. Rosy cheeks and friable hair. Low serum copper [XR]

Neuropsychiatric + liver disease presentation due to copper build up [AR, ATP7B gene]