Protein metabolism Flashcards
Intellectual disability, autism, eczema, seizure, mousy odor of urine
Phenylketonuria (PAH)
PKU treatment
PKU-restricted diet
Large neutral AA supplement
Sapropterin (BH4)
Palynziq (pegvaliaes-pqpz; phe ammonia lyase)
Enzymes that use biopterin (BH4)
Tryptophan, phenylalanine, and tyrosine hydroxylase + NO synthase, neurotransmitters
Ddx for high Phe
Benign hyperPhe (<360), PKU, DHPR deficiency (activity in RBC), disorders of BH4 synthesis (pterin metabolites in urine)
Developmental delay, hypotonia of trunk + hypertonia of extremities, tremors, conclusions, high Phe
GTP cyclohydrolase I deficiency, AR (GCH1). Low urine biopterin & neopterin, low CSF HVA, 5-HIAA. AD form normal Phe, reduced penetrance, dopa-responsive dystonia
Abnormal movements, DD, prematurity, low birth weight, high Phe. (Up to 1/3 present in infancy instead w/movement disorder)
PTPS deficiency, AR (PTS): high urine monapterin, low biopterin; CSF low HVA and 5-HIAA
Most asymptomatic, some with transient hypotonia, normalization of Phe in infancy
PCD deficiency, AR (PCBD1): normal CSF
Significant delays despite Phe restriction, brain abnormalities, prone to sudden death, high Phe
Dihydropteridine reductase deficiency, AR (QDPR): high urine biopterin, low CSF HVA and 5-HIAA, low RBC DHPR activity.
DD, inconsolable, dopa-responsive dystonia, psychiatric symptoms, normal Phe
Sepiapterin reductase deficiency, AR (SPR): normal urine pterins, CSF high sepiaterin and biopterin, low HVA and 5-HIAA
DD, dopa-responsive movement disorder, mild hyperPhe, PAH sequence normal
DNAJC12 defects (chaperone for hydroxylase enzymes)
Newborn w/poor feeding, lethargy, coma, seizures, abnormal movements, tonic spasms, mild hypoglycemia and acidosis, ketonuria, sweet smell
MSUD (branched chain ketoacid dehydrogenase deficiency BCKDH - any of 4 subunits)
Newborn with coagulopathy, hepatomegaly, hyperbilirubinemia. No hypoglycemia or acidosis.
Tyrosinemia type 1 (fumarylacetoacetate hydrolase, FAH)
Tyrosinemia stages of symptoms
Early infancy: liver disease
Late infancy: Renal tubulopathy (Fanconi) -> rickets if untreated
Adolescence: porphyria-like attacks.
Risk of cirrhosis -> HCC
Treatment of tyrosinemia type 1 (prevention of succinylacetone accumulation)
Limitation of dietary protein (Phe/Tyr)
NTBC/nitisinone (blocks upstream pathway) - prevents HCC
Newborn with lethargy, poor feeding, and hiccups –> seizures, apnea, coma
Nonketotic hyperglycinemia (GLDC most commonly, AMT, or GCSH)
Age of presentation of NKH vs outcome
Neonatal: 85% severe w/o developmental progress, intractable epilepsy. >2 weeks, 50/50%, >3mo all attenuated some of whom do not have epilepsy and have some development
Treatment of NKH
Reduce glycine with Na benzoate; antagonize NMDA with dextromethorphan, ketamine, felbamate; AEDs except valproate
Newborn with elevated methionine, elevated homocysteine
Homocystinuria (cystathionine beta-synthase deficiency, CBS).
Sx of untreated homocystinuria
Marfanoid habitus and eye problems, DD, neuropsychiatric symptoms, recurrent VTE
Treatment of homocystinuria
Reduce protein intake, 50% responsive to pyridoxine, betaine (converts homocysteine back to methionine) with caution as Met >1000 leads to cerebral edema
Infant with IUGR, generalized ichthyosis, microcephaly (w/lissencephaly, hypoplasia), low serine and glycine on PAA. Most stillborn/die prenatally.
Neu-Laxova; severe serine biosynthesis defects (PHGDH, PSAT1, PSPH)
Infant with IUGR, microcephaly (atrophic brain w/hypomyelination, hypoplasia), irritability, epilepsy, spastic tetraplegia
Infantile serine biosynthesis defects (PHGDH, PSAT1, PSPH)
Childhood loss of night vision d/t chorioretinal atrophy, loss of peripheral vision, elevated ornithine
Gyrate atrophy of choroid and retina (ornithine aminotransferase deficiency, OAT)
Dark discoloration of sclerae and ears, arthritis
Alkaptonuria (dioxygenase) - homogentisic acid
